Asian Pacific journal of cancer prevention: APJCP

Print ISSN: 1513-7368
Percentage of Adults' Waking Hours Achieving Sedentary, Light Intensity and Moderate/ Vigorous Intensity of Physical Activity (after Owen et al., 2009)  
Costs of Physical Inactivity
Physical activity is an important determinant of both physical and psychological health. Regular physical activity exerts beneficial effects on onset and progression of a number chronic diseases, well-being, and has positive effect to communities and societies. Unfortunately, more than 60% of world-wide adults do not reach the recommended levels of physical activity. This paper presents the prevalence, health risks, and economic costs of physical inactivity. It also reports the substantial physical and psychological health benefits of regular physical activity.
HLA-DQB1 and HLA-DRB1 Allele Frequencies among Breast Cancer Patients and Control 
Background: In the literature, data concerning the relationship between breast cancer and HLA class II gene polymorphisms are limited, so the aim of this study was to determine if HLA-DQB1 and HLA-DRB1 MHC class-II alleles may confer susceptibility or resistance to the disease among Jordanian females. Materials and methods: This case control study enrolled 56 Royal Hospital breast cancer patients and 60 age matched healthy controls, all of whom provided blood samples (2011-2013). A questionnaire was filled after signing a consent form and DNA was extracted, nucleic acids being amplified for assessment of HLA-DQB1 and HLA-DRB1 alleles by muliplex INNO-LiPA and allele typing carried out by reverse hybridization. Comparison of HLA-DQB1 and HLA-DRB1 allele distributions was carried out with paired t-test and chi-square statistics. Risk factors were assessed by odd ratios with 95% confidence intervals. Results: A significant negative correlation was observed between HLADQB1* 02 alleles and breast cancers (p=0.013). No significant associations were observed among HLADQB1* 03, 04, 05 and 06 or among HLA-DRB1* 01, 03, 04, 07, 08, 10, 11, 13, 14 and 15. Conclusions: HLADQB1* 02 alleles may provide positive protection against breast tumor risk among Jordanians, but not HLADQB1* 03, 04, 05 and 06 or HLA-DRB1* 01, 03, 04, 07, 08, 10, 11, 13, 14 and 15 alleles.
Incidence Cases, Rates by Site and Age Group, Delhi Urban, 2004-05, Females 
There are no data available on cancer incidence pattern in rural Delhi. This is the first report on cancer incidence among Delhi Rural population during 2004-05 which gives the first hand information on cancer incidence. The data for this report has been collected by Delhi Population based cancer registry. The sources for cancer registration are more than 162 Government Hospitals/centers and 250 private hospitals and nursing homes. A total of 594 cancer cases with 317 males and 277 females were registered during the period 1st January 2004 to 31st December 2005. The age adjusted (world population) incidence rates for all sites were 55.2 per 100,000 for males and 47.7 per 100,000 for females. The leading sites of cancer among Delhi Rural males was oral cavity (ASR: 8.0 per 100000) followed by lung (ASR: 6.5), larynx (ASR: 4.0) and bladder (ASR: 4.1). In females cervix uteri (ASR: 10.3 per 100,000) was the most common site of cancer followed by breast (ASR: 7.8), gallbladder (ASR: 3.5) and ovary (ASR: 3.3). The overall incidence rates of cancer in Delhi Rural were comparatively very less than Delhi Urban. A statistically significant difference was also found between Delhi Rural and Delhi Urban in incidence rates (ASR) for first four common sites. The rates in Delhi Rural are also comparatively lower than other rural registries situated in India.
Population at Risk by Five Year Age Group and Sex, Delhi Urban, 2001-05 
Incidence Cases, Rates by Site and Age Group, Delhi Urban, 2001-05, Females 
The Delhi Population based cancer registry collects data on new cancer cases diagnosed among Delhi urban resident population. The sources for cancer registration are more than 162 government hospitals/centers and 250 private hospitals and nursing homes. During the period 1st January 2001 to 31st December 2005 a total of 54,554 cases were registered of which 28,262 were males and 26,292 were females. The age adjusted (world population) incidence rates were 116.9 per 100,000 for males and 116.7 per 100,000 for females. The leading sites of cancer among Delhi males was lung (ASR: 13.8 per 100,000) followed by oral cavity (ASR: 11.4), prostate (ASR: 9.0) and larynx (ASR: 7.9). In females, breast (ASR: 30.2 per 100,000) was the most common site of cancer, followed by cervix uteri (ASR: 17.5), ovary (ASR: 8.5) and gallbladder (ASR: 7.4). The incidence of prostate cancer in males and ovary cancer in females in Delhi were the highest among the Indian registries, while larynx among males was the second highest and the gallbladder cancer in females was the highest among Indian metropolitan cities.
The purpose of this study was to investigate 50 women from eight families with familial cervical cancer in Wufeng County, Hubei Province, China, a region with a high incidence of cervical cancer. Eighty-nine healthy women, of similar age, location and ethnicity, were selected as a control group. Blood samples were collected from both groups, and HLA-A, HLA-B, and HLA-DRB1 genotypes were profiled with the Multi-Analyte Profiling system (xMAP) (Luminex HLA-SSO) using a WAKFlow HLA typing kit. Results were analyzed with Luminex HLA typing software and showed good stability, reproducibility and specificity. We found several high risk alleles in women with familial cervical cancer, that associated with the highest risk being HLA-B*07 (OR = 8.7, 95% CI = 1.8-41.1). HLA-B*07 is a high risk allele for cervical cancer, and has strong potential for use as a molecular biomarker.
The Lao PDR is a landlocked country with 5,920,000 inhabitants for which very few epidemiological studies on cancer have been performed. The aim of the present study was to examine cancer mortality in 2007-2008. A descriptive cancer epidemiology protocol was designed with a data collection form and guideline for both demographics and list of all deaths from all 757 local Health Centers of 17 provinces/ cities. Five indicators, name, age, sex, date of death and the cause of death (ICD-10), were collected for each case. The age-specific cancer mortality rate and ASRs per 100,000 were estimated. There were 448 cancer cases reported from Health Centers within 7 of 17 provinces/cities. Number of person-years was 654,459 for the two-year period. Cancer mortality rates of all sites (ASR) were 116.7 and 97.2 per 100,000 in males and females, respectively. The five most common cancers causing mortality per 100,000 were liver (52.2), followed by colorectal (19.0), lung (17.3), stomach (6.9), and leukemia-lymphoma (7.2) in males and liver (28.4); followed by colorectal (19.0), lung (14.0), cervical uteri (9.2) and stomach (7.1) in females. Liver and colorectal cancers were the first and second most common, respectively, in both males and female.
To evaluate the clinical impact of preoperative serum CEA and CA19-9 on resectable gastric cancer (GC), a total of 1,075 consecutive cases with gastric adenocarcinoma were obtained retrospectively from January 2012 and December 2013 in a single tertiary hospital, and the relationships between serum CEA, CA19-9 and clinicopathologic features were investigated. Positive preoperative serum rates of CEA and CA19-9 were 22.4% and 12.3% respectively, levels significantly correlating with each other and depth of invasion, lymph node involvement, pTNM and stage. The CEA level also presented a remarkable association with lymphovascular invasion. Both CEA and CA19-9 positivity significantly and positively correlated with depth of invasion, nodal involvement, pTNM stage, lymphovascular invasion, tumor size and tumor location. Stratified analyses according to gender or tumor location showed preoperative CEA or CA19-9 had different associations with clinicopathologic features in different gender subgroups or location subgroups. Preoperative serum CA19-9 positivity may be more meaningful for tumor size rather than CEA. In conclusion, preoperative serum CEA and CA19-9 correlate with disease progression of GC, and may have applications in aiding more accurate estimation of tumor stage, decision of treatment choice and prognosis evaluation.
Purpose: To evaluate the efficacy and toxicity of induction chemotherapy followed by concurrent chemoradiotherapy (the treatment group) versus concurrent chemoradiotherapy with or without adjuvant chemotherapy (the control group) for locoregionally advanced nasopharyngeal carcinoma. Methods: The search strategy included Pubmed, Embase, the Cochrane Library, China National Knowledge Internet Web, Chinese Biomedical Database and Wanfang Database. We also searched reference lists of articles and the volumes of abstracts of scientific meetings. All randomized controlled trials were included for a meta-analysis performed with RevMan 5.1.0. The Grading of Recommendations Assessment, Development, and Evaluation system (GRADE) was used to rate the level of evidence. Results: Eleven studies were included. Risk ratios of 0.99 (95%CI 0.72-1.36), 0.37 (95%CI 0.20-0.69), 1.08 (95%CI 0.84-1.38), 0.98 (95%CI 0.75-1.27) were observed for 3 years overall survival, 3 years progression-free survival, 2 years loco-regional failure-free survival and 2 years distant metastasis failure-free survival. There were no treatment-related deaths in either group in the 11 studies. Risk ratios of 1.90 (95%CI 1.24-2.92), 2.67 (95%CI 0.64-11.1), 1.04 (95%CI 0.79-1.37), 0.98 (95%CI 0.27-3.52) were found for grade 3-4 leukopenia, grade 3-4 thrombocytopenia, grade 3-4 mucous membrane, and grade 3-4 hepatic hematologic and gastrointestinal toxicity, the most significant toxicities for patients. Conclusion: Compared with the control group, induction chemotherapy followed by concurrent chemoradiotherapy was well tolerated but could not significantly improve prognosis in terms of overall survival, loco-regional failure-free survival or distant metastasis failure-free survival.
Aberrant crypt foci (ACF) are recognized as preneoplastic lesions for colon cancer, and ACF in rodents are widely used as an intermediate biomarker to predict tumorigenicity in the colon. However, a lack of correlations between the formation of ACF and the development of colonic tumors has been reported in several studies. For example, 2-(carboxyphenyl) retinamide (2-CPR) and genistein were reported to inhibit the carcinogen-induced formation of ACF, whereas both of them were later found to enhance colon tumorigenesis in rats treated with azoxymethane (AOM). Recently, we have identified b-catenin-accumulated crypts (BCAC) in the colon of rats shortly after administration of AOM, and provided evidence that these are independent early lesions of classical ACF, and BCAC might be direct precursors for colon cancers. In the present study, we performed a comparative analysis of the modifying effects of 2-CPR and genistein on 1,2-dimethylhydrazine (DMH)-induced BCAC and ACF in male F344 rats. Dietary administration of 2-CPR (315 ppm) significantly reduced the total number, multiplicity and size of ACF in DMH-exposed colonic mucosa, while genistein (250 ppm) had no significant effects on DMH-induced ACF formation. In contrast, both of 2-CPR and genistein significantly enhanced the multiplicity and size of DMH-induced BCAC when compared with DMH alone group. In addition, both 2-CPR and genistein significantly increased the proliferating cell nuclear antigen (PCNA) index preferentially in BCAC. Together with previous findings that 2-CPR and genistein are tumor promoters in the colon, our results support the concept that BCAC are precursors of colon tumors and suggest that these lesions are more reliable short-term biomarkers for colon carcinogenesis in rodents than ACF.
shows the morphological features of the colons after a period of six weeks showing the mucosal surface depicting the occurrence of MPLs, recognized as either raised or non-raised stretches in the form of identifiable tissue growth, often appearing singly or in multiple forms throughout the length of the colon. A few MPLs were observed in control and etoricoxib animals. Maximum numbers of MPLs however, were observed in DMH treated animals but the number was found much less in DMH+etoricoxib treated animals (Table 1). DMH treated animals show severe dysplasia and hyperplasia of crypt cells. The nuclei were also deeply stained and oval in shape in DMH treated animals, whereas in control animals no such features were observed. The simultaneous administration of DMH and Etoricoxib reduced these features of dysplasia and hyperplasia. No such features were observed in the Etoricoxib only group. The control group showed maximum number of apoptotic cells whereas the number of such cells was highly reduced in DMH treated animals, this being reversed in DMH + Etoricoxib group (Table 2). Similarly, in the DMH treated group, the intensity of the bands of fragmented DNA which is indicative of the apoptotic process, was the lowest. With Etoricoxib treatment however, the intensity had increased indicating the restoration of apoptosis. The expression of PCNA was found to be higher in DMH treated group as compared to the Control. The expression was found to be low in Etoricoxib only group. In DMH + Etoricoxib group also, the expression was found to be low as compared to control, whereas it was much less than in the DMH group (Figure 2). The expression of both PCNA and BrdU was found to be higher in the paraffin tissue sections in DMH treated group as compared to the Control. The expression was found to be low in Etoricoxib only group. In DMH + Figure 1. Morphological Appearance Control DMH DMH+Etoricoxib Etoricoxib
Expression of PCNA
In the present study, we assessed effects of etoricoxib, a non-steroidal anti-inflammatory drug, on proliferation and apoptosis in 1,2-dimethylhydrazine dihydrochloride (DMH) induced colon lesion development. Male SD rats were divided into four groups: Group 1 controls receiving the vehicle treatment; Group 2 administered DMH weekly (30 mg/kg body weight, subcutaneously) alone; Group 3, DMH weekly plus etoricoxib (0.64 mg/kg body weight, orally) daily; and Group 4, etoricoxib alone. After six weeks of treatment, animals were sacrificed and colons were analysed for morphological and histopathological features. Well characterized pre-neoplastic aberrations such as multiple plaque lesions, hyperplasia and dysplasia were found in the DMH treated group whereas these features were reduced with co-administration of etoricoxib. To study apoptosis, colonocytes were isolated by metal chelation from colonic sacs and studied by fluorescent staining and further confirmed by DNA fragmentation. The DMH treated animals had fewer apoptotic nuclei as compared to the controls, but numbers were higher with DMH+etoricoxib as well as etoricoxib alone. Expression of proliferative cell nuclear antigen (PCNA), assessed by Western blot analysis and immunohistochemistry, was found to be elevated by DMH treatment group and again reduced by etoricoxib. Results for bromodeoxyuridine incorporation (BrdU) were in agreement. It may be concluded that the drug, etoricoxib, has the potential to act as an anti-apoptotic and anti- proliferative agent in the colon.
High temperature- and pressure-treated garlic (HTPG) has been reported to have enhanced antioxidative and cytotoxic activities. However, there have been no reports on chemopreventive effects using animal cancer models. This study first examined the modifying effects of HTPG on 1,2-dimethylhydrazine (DMH)-induced mucin-depleted foci (MDF) and aberrant crypt foci (ACF), preneoplastic lesions in the rat colorectum. Male F344 rats (5 weeks old) were fed basal diet, or experimental diets containing 1% or 3% HTPG for 5 weeks. One week later, all rats were injected s.c.with DMH (40 mg/kg, once weekly for 2 weeks). At 10 weeks of age, all the rats were sacrificed, and the colorectum was evaluated for MDF and ACF. In rats given DMH and 3% HTPG, the numbers of MDF were decreased significantly as compared with those of rats given DMH alone (p< 0.01), and the numbers of ACF showed a tendency to decrease, although not significantly. Next, the effects of HTPG on the formation of DMH-induced O6-methylguanine (O6-MeG) DNA adducts in rats were studied. Male F344 rats (5 weeks old) were fed the basal diet or 10% HTPG diet for 5 weeks. All rats were injected i.p. once with 40 mg/kg DMH at the end of week 5. The animals were sacrificed 6 hours after DMH injection to analyze the O6-MeG DNA adducts in the colorectal mucosa and liver. Dietary administration of HTPG significantly reduced the adduct levels in the colorectal mucosa and liver, compared with the controls (both p< 0.01). The activities of some detoxification enzymes in the liver of DMH-treated rats were also measured. HTPG significantly reduced the activity of cytochrome P450 (CYP) 2E1, known to be responsible for activation of DMH in rat liver (p< 0.05). In contrast, HTPG significantly enhanced the activities of phase 2 enzymes, quinone reductase (QR) and glutathione S-transferase (GST), in rat liver (both p< 0.05). These results suggested that HTPG might have chemopreventive effects against colon carcinogenesis, at least in the initiation stage.
Colon cancer is the third most common malignant neoplasm in the world and it remains an important cause of death, especially in western countries. The toxic environmental pollutant, 1, 2-dimethylhydrazine (DMH), is also a colon-specific carcinogen. Tannic acid (TA) is reported to be effective against various types of chemically induced toxicity and also carcinogenesis. In the present study, we evaluated the chemopreventive efficacy of TA against DMH induced colon toxicity in a rat model. Efficacy of TA against the colon toxicity was evaluated in terms of biochemical estimation of antioxidant enzyme activities, lipid peroxidation, histopathological changes and expression of early molecular markers of inflammation and tumor promotion. DMH treatment induced oxidative stress enzymes (p<0.001) and an early inflammatory and tumor promotion response in the colons of Wistar rats. TA treatment prevented deteriorative effects induced by DMH through a protective mechanism that involved reduction of oxidative stress as well as COX-2, i-NOS, PCNA protein expression levels and TNF-α(p<0.001) release. It could be concluded from our results that TA markedly protects against chemically induced colon toxicity and acts plausibly by virtue of its antioxidant, anti-inflammatory and antiproliferative activities.
Etoricoxib, a highly selective cyclooxygenase- 2 (COX-2) inhibitor (a non steroidal anti-inflammatory drug) used for the treatment of rheumatoid arthritis and osteoarthritis, has been newly marketed and studied for the chemopreventive response in the 1,2-dimethylhydrazine dihydrochloride (DMH) induced rat colon cancer model. Male Sprague-Dawley rats were divided into four groups. Group I served as the Control and received the vehicle treatment, while Groups 2 and 3 were administered freshly prepared DMH (30 mg/kg body weight, subcutaneously) in 1mM EDTA-saline (pH 7.0). Groups 3 and 4 received Etoricoxib (0.64 mg/kg body weight, orally) daily prepared in 0.5% carboxymethyl cellulose. After a 6 week treatment period, animals were sacrificed and the colons were subjected to macroscopic and histopathological studies. Well characterized pre-neoplastic features such as multiple plaque lesions (MPLs), aberrant crypts (ACs) and aberrant crypt foci (ACF) were found in the DMH group. The number was reduced in DMH + Etoricoxib group, while very few MPLs and ACFs were recorded in the Etoricoxib only group. Also, histologically well characterized dysplasia and hyperplasia were observed in DMH treated group. The simultaneous administration of DMH and Etoricoxib reduced these features. To study apoptosis, colonocytes were isolated by metal chelation from colonic sacs and studied by fluorescent staining. The DMH treated animals produced much less apoptotic nuclei as compared to the Control. The number of apoptotic nuclei was also found higher in the DMH + Etoricoxib group as well as in Etoricoxib only group. Studies of a nuclear transcription factor (NF-kB) and COX-2 by Western blot analysis and immunohistochemistry demonstrated expression of both to be elevated in the DMH treated group but reduced in the DMH + Etoricoxib group. Expression was also low in the Etoricoxib only group. It may be concluded that the drug, Etoricoxib, has the potential to reduce DMH induced colon cancer development.
Non-Hodgkin's lymphomas (NHL) in China appear to have many characteristics different from those Western countries, but clinical studies to provide details have been rare so far. This study retrospectively analyzed the characteristics of clinical and pathological data for the 1248 NHL patients in the Shandong region of China between 2002 and 2010. From 2002 to 2010, the number of clinical cases of NHL increased year by year. Among the total, 64.7% were B-cell NHL, 30.3% were T-cell NHL, including: diffuse large B cell lymphoma (DLBCL) (40.9%), extranodal NK/T-cell lymphoma, nasal type (NK/T) (10.0%); peripheral T cell lymphoma, unspecified (PTL) (9.2%); follicular lymphoma (FL) (6.4%); extranodal marginal zone B cell lymphoma (MALT) (5.4%); precursor T lymphoblastic leukemia/lymphoma (T-LBL) (4.5%); and chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) (3.2%). The average age of onset was 47.7 ∓ 16.3 (18-85), and the male to female ratio was 1.57:1. Compared with Shanghai and Shanxi in China, the proportion of NK/T cell lymphoma in this region was higher. In comparison with other countries, the FL and CLL/SLL in this region were significantly lower, while the incidence of T-cell lymphoma was significantly higher than that in the United States and Europe. The clinical and pathological distribution of NHL in Shandong region of China is consistent with that of Asian populations, but with significant difference from the Western countries. The NK/T cell lymphoma in this region was significantly higher.
Effect of β-carotene on the Growth of EC9706 Cells. Cells were incubated in presence of the indicated doses of β-carotene for 12, 24 and 48 hr, respectively. And cell proliferation was determined by a 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Results are presented as percentages of control. Data are shown in the mean±S.D. (n = 3). * p < 0.05, versus the control group 
Effect of 1,25-dihydroxyvitamin D3 on the Growth of EC9706 Cells. Cells were incubated in presence of the indicated doses of 1,25-dihydroxyvitamin D3 for 12, 24 and 48 hr, respectively. And cell proliferation was determined by a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Results are presented as percentages of control. Data are shown in the mean±S.D. (n = 3). * p < 0.05, versus the control group 
Effect of the Combination of β-carotene and 1,25-dihydroxyvitamin D3 on the Growth of EC9706 Cells. Cells were incubated in presence of the indicated doses of β-carotene and/or 1,25-dihydroxyvitamin D3 for 12, 24 and 48 hr, respectively. And cell proliferation was determined by a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Results are presented as percentages of control. Data are shown in the mean±S.D. (n = 3). * p < 0.05, versus the control group. ** p < 0.05, versus both 80 μM β-carotene treatment group and 80 μM 1,25-dihydroxyvitamin D3 treatment group 
Effect of β-carotene and 1,25-dihydroxyvitamin D3 in Combination Acted on Cell Cycle Distributions and Apoptosis in EC9706 Cells. EC9706 cells were treated with β-carotene (80 μM) and/or 1,25-dihydroxyvitamin D3 (80 μM) for 48 hr. Then, cells were analysed by flow cytometry after PI staining and the relative percentage of cells in different cell cycle phases and apoptosis was reported. (B) The results are expressed as the percentage of the cell cycle distribution. (C) The results are expressed as the percentage of the cell apoptosis. * p < 0.05, versus the control group. ** p < 0.05, versus both 80 μM β-carotene treatment group and 80 μM 1,25-dihydroxyvitamin D3 treatment group 
Esophageal cancer is a common malignant tumor occurring in human esophageal epithelial tissue. The primary purpose of this paper was to define the effects of β-carotene and 1,25-dihydroxyvitamin D3, alone and in combination, on cell proliferation, cell cycle and apoptosis of human esophageal cancer EC9706 cells. Treatment with different concentrations of β-carotene and/or 1,25-dihydroxyvitamin D3. MTT assay showed that β-carotene and 1,25-dihydroxyvitamin D3 significantly inhibited proliferation of EC9706 cells in a dose- and time-dependent manner. Further studies also demonstrated that β-carotene alone or 1,25-dihydroxyvitamin D3 alone caused a marked increase on the induction of apoptosis in EC9706 cells. The percentage of G0/G1-phase cells significantly increased on addition of 1,25-dihydroxyvitamin D3 alone, but there were no significant changes with β-carotene alone. These two agents in combination synergistically inhibited cell growth and induced apoptosis. Therefore, our results indicate that β-carotene and 1,25-dihydroxyvitamin D3 in combination may provide a novel strategy for preventing and treating esophageal cancer.
Background: DICER, one of the microRNA (miRNA) biogenesis proteins, is involved in the maturation of miRNAs and is implicated in cancer development and progression. The results from previous epidemiological studies on associations between DICER rs1057035 polymorphism and cancer risk were inconsistent. Thereforewe performed this meta-analysis to summarize possible associations. Materials and methods: We searched all relevant articles on associations between DICER rs1057035 polymorphism and cancer risk from PubMed, EMBASE, Chinese Biomedical Literature and Chinese National Knowledge Infrastructure until August 2014. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to assess any associations. Heterogeneity tests, sensitivity analyses and publication bias assessments were also performed in this meta-analysis. All analyses were conducted using STATA software. Results: Seven case-control studies, including 4,875 cancer cases and 7,800 controls were included in the meta-analysis. Overall, the results indicated that the C allele of DICER rs1057035 polymorphism was significantly associated with decreased cancer risk in allelic comparison, heterozygote and dominant genetic models (C vs T: OR=0.88, 95%CI 0.81-0.95, p=0.002; TC vs TT: OR=0.85, 95%CI 0.77-0.93, p=0.001; CC/TC vs TT: OR=0.86, 95%CI 0.78-0.94, p=0.001). In the subgroup analysis by ethnicity, a significantly decreased cancer risk was found in Asian but not Caucasian populations. Conclusions: The present meta-analysis suggests that the C allele of the DICER rs1057035 polymorphism probably decreases cancer risk. However, this association may be Asian-specific and the results should be treated with caution. Further well-designed studies based on larger sample sizes and group of populations are needed to validate these findings.
Many epidemiological studies in Asian populations have investigated associations between the Arg399Gln gene polymorphism of X-ray repair cross complementing gene 1 (XRCC1) and risk of cervical carcinoma, but no conclusions have been available because of controversial results. Therefore a meta-analysis was conducted for clarification. Relevant studies were identified by searching the Pubmed, Embase, the Web of Science, Cochrane Collaboration's database, Chinese National Knowledge Infrastructure (CNKI), Wanfang database and China Biological Medicinse (CBM) until September, 2012. A total of eight studies were included in the present meta- analysis, which described 1,759 cervical carcinoma cases and 2,497 controls. Odds ratios (ORs) and corresponding 95% confidence intervals (95%CIs) as effect size were calculated by fixed-effect or random-effect models. The overall results indicated that the XRCC1-399G/A polymorphism was marginally associated with cervical carcinoma in Asians: OR (95%CI): 1.16 (1.07, 1.26) in the G/A vs G/G inheritance model, 1.24 (0.87, 1.76)in A/A vs G/G inheritance model, 1.13 (1.01, 1.27) in the dominant inheritance model and 1.18 (0.94, 1.47) in the recessive inheritance model. Subgroup analyses on sample size showed no significant correlation in the small- sample size group but the large-sample size group was consistent with the outcomes of overall meta-analysis. In the subgroup analysis by regions, we only found significant association under the G/A vs G/G inheritance model in the Chinese population. For the non-Chinese populations, no correlation was detected in any genetic inheritance model. In the Asian populations, XRCC1-399G/A gene polymorphism was implied to be associated with cervical carcinoma.
The interleukin-18 promoter -607C>A gene polymorphism may be related to nasopharyngeal carcinoma (NPC) risk but the results of individual studies remain conflicting. A meta-analysis including 1,886 subjects from five individual studies was therefore performed to provide a more accurate estimation. Pooled odds ratios (ORs) and their corresponding 95% confidence intervals (95% CIs) were evaluated by fixed- or random-effects models. A significant relationship between interleukin-18 promoter -607C>A gene polymorphism and NPC was found in a dominant genetic model (OR: 1.351, 95% CI: 1.089-1.676, P=0.006, Pheterogeneity=0.904), a homozygote model (OR: 1.338, 95% CI: 1.023-1.751, P=0.034, Pheterogeneity=0.863), and a heterozygote model (OR: 1.357, 95% CI: 1.080-1.704, P=0.009, Pheterogeneity=0.824). No significant association was detected in either an allelic genetic model (OR: 1.077, 95% CI: 0.960-1.207, 0.207, Pheterogeneity=0.844) or a recessive genetic model (OR: 1.093, 95% CI: 0.878-1.361, P=0.425, Pheterogeneity=0.707). In conclusion, a significant association was found between interleukin-18 promoter -607C>A gene polymorphism and NPC risk. Individuals with the C allele of interleukin-18 promoter -607C>A gene polymorphism have a higher risk of NPC development.
The APJCP Impact Factor for 2012 is 1.271, returning from 0.659 for 2011 (1.240 for 2010 and 1.108 for 2009). For an Asian Pacific journal publishing over 100 papers a month from countries with very varied resources it is heartening and we thank all those who continued to submit papers and cite references in the APJCP through our difficult period. However, we still have very much room for improvement. As Chief Editors it is our shared responsibility to act for the benefit of the cancer control research community who utilize the journal in our region of over four billion people and provide a prestigious forum for publication of research findings which can be freely shared by all. The motivation for the APOCP/APJCP has never been financial profit but a firm financial base is nevertheless essential. Although we have kind support from the Korean National Cancer Center for our Managing Editor and the website, our ability to maintain our Chinese and Thai offices is totally dependent on the processing charges paid by the authors. In order to expand our staff to cope with increased submissions and provide greater assistance in ensuring comprehensive reference coverage and dissemination of findings published in the APJCP to the worldwide research community, a joint decision has been made to increase formatting charges by 50% from July. We ask for author understanding. In addition, we appeal to scientists to positively consider our requests to make their reference lists as comprehensive as possible, including papers from the APJCP where appropriate. The future of the journal and the APOCP is largely in your own hands.
Background: To evaluate the performance of Siriraj liquid-based cytology (LBC) for cervical neoplasia screening after increasing use of this technology. Materials and methods: Cytological reports of 103,057 Siriraj-LBC specimens obtained in 2007-2009 were compared with those of 23,676 specimens obtained in 2006. Results: Comparing with the year 2006, the 2007-2009 patients were slightly older (43.4 ± 12.yr vs 42.7 ± 12.2 yr, p <0.001), and their specimens had much lower proportion of unsatisfactory slides (OR=0.06, 95%CI 0.04-0.09) with comparable detection rates (3.96% vs 3.70%, p=0.052) but different proportions of various cytological abnormalities (p<0.001). The 2007-2009 Siriraj-LBC had a negative predictive value (NPV) for cervical intraepithelial neoplasia 2+ (CIN2+) of 97.6% and an overall positive predictive value (PPV) of 43.9%. The PPV for CIN2+ varied with types of abnormal cytology, from 13.7% to 93.8% in atypical squamous cells of undetermined significance (ASCUS), low-grade squamous intraepithelial lesion (LSIL), atypical squamous cells cannot exclude HSIL (ASC-H), high-grade squamous intraepithelial lesion (HSIL), atypical glandular cells (AGC), to squamous cell carcinoma (SCC), respectively. The PPVs for CIN2+ in ASCUS and LSIL were comparable, but the PPV for CIN1 was higher for LSIL than for ASCUS (41.63% vs 16.32%). Conclusions: Siriraj-LBC has demonstrated a stable detection rate and NPV for CIN2+ of >95% since the first year of use. The comparable PPVs for CIN2+ of ASCUS and LSIL suggests that these two conditions may undergo similar management; other cytological abnormalities need immediate evaluation.
Clinical and Pathological Parameters of Patients
Objective: This work aimed to investigate the correlations of tumor-associated macrophages (TAMs) and their subtypes M1 and M2 with liver metastasis of colorectal cancer, and provide useful references for seeking predictors of liver metastasis and studying mechanisms. Methods: 120 patients with colorectal cancer from 2000 to 2009 were divided into low, middle and high liver metastasis groups (group A, B and C, respectively). S-P immunohistochemical staining and microscopic observation were conducted to compare expression in CD68- positive cells (TAMs), CD80-positive cells (M1) and CD163-positive cells (M2) in three groups. Correlations of TAMs, M1, M2, and M2/M1 ratio with clinical and pathological parameters were analyzed. Results: With increase of liver metastatic ability, the number of TAMs decreased gradually, with no significant difference between any two of the three groups (P > 0.05), while the numbers of M1 and M2 were significantly decreased and increased, respectively, with significant difference between any two of three groups (P < 0.05 or P < 0.01). In addition, the M2/M1 ratio increased with increase of liver metastatic ability (P < 0.01). There was no statistical significance of correlation of TAMs with each clinical and pathological parameter. M1 was negatively related with lymphatic metastasis and liver metastatic ability. M2 was positively correlated with preoperative CEA level, lymphatic metastasis, tumor differentiation degree and liver metastatic ability. The same was the case for the M2/M1 ratio. Conclusions: Effects of TAMs on liver metastasis of colorectal cancer do not depend on the total number of TAMs, but on the number and proportion of functional subtypes M1 and M2. M2 number and M2/ M1 ratio are more accurate predictors for liver metastasis of colorectal cancer.
Background: The infusion rate is considered to affect incidence and severity of infusion reactions (IRs) caused by protein formulations. Trastuzumab (TRS) is approved for 90-minute infusion as the initial dose followed by 30-minute infusion with 250 ml saline. In the study, we evaluated the safety of TRS intravenously administered over 30 minutes with 100 ml saline to reduce burden of patients, safety of infusion with 250 ml saline already being established. Materials and methods: Women with HER2 positive breast cancer, ≥18 years and ≥55% left ventricular ejection fraction (LVEF), were registered in the study. Patients received 8mg/kg of TRS 250 ml over 90 minutes followed by 6mg/kg of TRS 100ml over 30 minutes in a three-week cycle. Results: A total of 31 patients were recruited, 24 for adjuvant therapy and seven with metastases. The median age was 59 years (range 39 to 82). The total number of TRS doses ranged from 5 to 17 with the median of 15. Mild IR occurred in two patients at the first dose. However, no IR was observed after reducing to 100 ml saline. No decrease of LVEF, increase of serum brain natriuretic peptide or any other adverse events were reported. Conclusions: Intravenous infusion of TRS with 100 ml saline over 30 minutes in breast cancer patients can be considered safe based on results from the study. It can be given on an outpatient basis as with the currently recommended dilution in 250 ml saline.
Aims: Early diagnosis is important for cervical cancer treatment. This study aimed to characteriz the microRNA profile and target gene protein levels of cervical cancers in Uygur women for application in early diagnosis. Methods: The profiles of miRNA in cervical cancer and chronic cervicitis were analyzed with miRNAmicroarray V4.0. The expression of miR-101 was detected by real-time PCR and locked nucleotide acid in situ hybridization (LNA-ISH). Cox-2 protein levels were assessed by immunohistochemistry. Results: The microarray identified a set of 12 miRNAs significantly decreased in cervical cancer in comparison to the control group. Quantitative RT-PCR analysis showed miR-101 to be significantly downregulated in cancer tissues (p<0.05) while LNA-ISH showed miR-101 positive rates of 80% (20/25) and 8% (5/25) (p<0.05) in the control and cervical cancer groups. Cox-2 positive rates of cervical cancer and control groups were 84% (21/25) and 8% (2/25) (p<0.05). Conclusions: Use of down-regulation of miR-101 and up-regulation of Cox-2 as markers may play a role in early diagnosis of cervical cancer in Uygur women.
Aim: Although aberrant miRNA expression has been documented, altered miR-101 expression in cervical cancer and its carcinogenic effects and mechanisms remain unexplored. The aim of our study was to investigate the role of miR-101 alteration in cervical carcinogenesis. Methods: Expression of miR-101 was examined by quantitative real-time reverse transcriptase PCR (qRT-PCR) in Hela cells. After modulating miR-101 expression using miR-101 mimics, cell growth, apoptosis and proliferation, and migration were tested separately by MTT or flow cytometry and cell wound healing assay and protein expression was detected by qRT-PCR. The expression of COX-2 in Hela cell was also examined by immunohistochemical staining and the correlation with miR-101 expression was analysed. Results: The miR-101 demonstrated significantly low expression in Hela cell. When we transfected miR-101 mimics into Hela cells, the modulation of miR-101 expression remarkably influenced cell proliferation, cycling and apoptosis: 1) The expression of microRNA-101 tended to increase after transfection; 2) Overexpression of miR-101 was able to promote cell apoptosis, the apoptosis rate being markedly higher (97.6%) than that seen pre-transfection (12.2%) (P <0.05); 3) The miR-101 negatively regulates cell migration and invasion, scratch results being lower (42.7um±2um) than that observed pre-transfection (181.4 um±2 um); 4) miRNA-101 inhibits the proliferation of Hela cells as well as the level of COX-2 protein, which was negatively correlated with miR-101 expression. Conclusions: Overexpression of miR-101 has obvious inhibitory effects on cell proliferation, migration and invasion. Thus reduced miR-101 expression could participate in the development of cervical cancer at least partly through loss of inhibition of target gene COX-2, which probably occurs in a relative late phase of carcinogenesis. Our data suggest an important role of miR-101 in the molecular etiology of cancer and indicate potential application of miR-101 in cancer therapy.
BRCA1 Deleterious Mutation in North-Eastern Breast Cancer Patients, India
Around 1.35 million people of worldwide suffer from breast cancer each year, whereas in India, 1 in every 17 women develops the disease. Mutations of the Breast Cancer 1 (BRCA1) gene account for the majority of breast/ ovarian cancer families. The purpose of study was to provide a prevalence of BRCA1 germline mutations in the North-East Indian population. In relation to the personal and family history with the breast cancer, we found mutations in 6.25% and 12.5% respectively. Three mutations, 185DelAG, 1014DelGT and 3889DelAG, were observed in our North-East Indian patients in exons 2 and 11, resulting in truncation of the BRCA1 protein by forming stop codons individually at amino acid positions 39, 303 and 1265. Our results point to a necessity for an extensive mutation screening study of high risk breast cancer cases in our North-East Indian population, which will provide better decisive medical and surgical preventive options.
The mismatch repair system (MMR) is a post-replicative DNA repair mechanism whose defects can lead to cancer. The MSH3 protein is an essential component of the system. We postulated that MSH3 gene polymorphisms might therefore be associated with prostate cancer (PC). We studied MSH3 codon 222 and MSH3 codon 1036 polymorphisms in a group of Iranian sporadic PC patients. A total of 60 controls and 18 patients were assessed using the polymerase chain reaction and single strand conformational polymorphism. For comparing the genotype frequencies of patients and controls the chi-square test was applied. The obtained result indicated that there was significantly association between G/A genotype of MSH3 codon 222 and G/G genotype of MSH3 codon 1036 with an increased PC risk (P=0.012 and P=0.02 respectively). Our results demonstrated that MSH3 codon 222 and MSH3 codon 1036 polymorphisms may be risk factors for sporadic prostate cancer in the Iranian population.
Genotype of Wild Type Sequence of Tyrosine 1045 Codon within Exon 27 of EGFR Gene. The wild type sequence TAC (indicated by a blue underline) that codes for the amino acid tyrosine remained unchanged in the thirty five oral squamous cell carcinoma tissue samples  
Background: The activation and inactivation of receptor tyrosine kinases are tightly regulated to ensure faithful replication of cells. After having transduced extracellular growth activating signals, activated EGFR is subjected to downregulation either by clathrin mediated endocytosis or c-Cbl mediated proteasome degradation depending on the ligand concentration. c-Cbl is an ubiquitin ligase which requires a phosphorylated tyrosine residue at position 1045 in the cytoplasmic domain of EGFR to interact and add ubiquitin molecules. While activating mutations in exons 19 and 21 have been associated with the development of several cancers, the status of mutations at tyrosine 1045 coding exon 27 of EGFR remain to be investigated. Consistently, defective phosphorylation at 1045 has been associated with sustained phosphorylation of EGFR in non-small lung carcinomas. Hence in the present study we investigated the genetic status of the tyrosine 1045 coding site within exon 27 of EGFR gene to explore for possible occurrence of mutations in this region, especially since no studies have addressed this issue so far. Materials and methods: Tumor chromosomal DNA isolated from thirty five surgically excised oral squamous cell carcinoma tissues was subjected to PCR amplification with intronic primers flanking the tyrosine 1045 coding exon 27 of EGFR gene. The PCR amplicons were subsequently subjected to direct sequencing to elucidate the mutation status. Results: Sequence analysis identified no mutations in the tyrosine 1045 codon of EGFR in any of the thirty five samples that were analyzed. Conclusions: The lack of identification of mutation in the tyrosine 1045 codon of EGFR suggests that mutations in this region may be relatively rare in oral squamous cell carcinomas. To the best of our knowledge, this study is the first to have explored the genetic status of exon 27 of EGFR in oral squamous cell carcinoma tissue samples.
Objective: The current meta-analysis was performed to address a more accurate estimation of the association between glutathione S-transferase P1 (GSTP1) codon 105 polymorphism and risk of gastric cancer (GC), which has been widely reported with conflicting results. Methods: A comprehensive literature search was conducted to identify all the relevant studies. Fixed or random effect models were selected based on the heterogeneity test. Publication bias was estimated using Begg's funnel plots and Egger's regression test. Results: A total of 20 studies containing 2,821 GC cases and 6,240 controls were finally included in the analyses. Overall, no significant association between GSTP1 polymorphism and GC risk was observed in worldwide populations. However, subgroup analysis stratified by ethnicity showed that GSTP1 polymorphism was significantly associated with increased risk of GC in Asians (G vs. A, OR = 1.273, 95%CI=1.011-1.605; GG vs. AA, OR=2.103, 95%CI=1.197- 3.387; GG vs. AA+AG, OR =2.103, 95%CI=1.186-3.414). In contrast, no significant association was found in Caucasians in any genetic models, except for with AG vs. AA (OR=0.791, 95%CI=0.669-0.936). Furthermore, the GSTP1 polymorphism was found to be significantly associated with GC in patients with H. pylori infection and in those with a cardiac GC. Subgroup analysis stratified by Lauren's classification and smoking status showed no significant association with any genetic model. No studies were found to significantly influence the pooled effects in each genetic mode, and no potential publication bias was detected. Conclusions: This meta-analysis suggested that the GSTP1 polymorphism might be associated with increased risk of GC in Asians, while GSTP1 heterozygote genotype seemed to be associated with reduced risk of GC. Since potential confounders could not be ruled out completely, further studies are needed to confirm these results.
Objective: To investigate the effects of miR-106b on malignant characteristics of gastric cancer cells, and explore possible mechanisms. Methods: Expression of miR-106b, p21 and E2F was determined by real-time PCR. Transfection with miR-106b mimics was conducted, and gastric cancer cells with miR-106b overexpression were obtained. Cells transfected with mimic mutants and those without transfection served as negative and blank controls, respectively. Flow cytometry and transwell assays were adopted to detect the effects of miR-106b overexpression on cell cycle, migration and invasion of gastric cancer cells. Results: . The expression of miR- 106b in gastric cancer cells was significantly higher than that in normal gastric mucosa cells. Furthermore, the expression level of miR-106b rose according to the degree of malignacy among the three GC cell strains (MKN- 45 > SGC-7901 > MKN-28). Overexpression of miR-106b shortened the G0/G1 phase and accelerated cell cycle progression, while reducing p21 and E2F5, without any significant effects on the capacity for migration and invasion of gastric cancer cells. Conclusions: miR-106b may promote cell cycling of gastric cancer cells through regulation of p21 and E2F5 target gene expression.
Genetic polymorphisms may modify the effects of environmental risk factors on cancer occurrence. We have recently launched a comprehensive epidemiologic project, HERPACC II (Hospital-based Epidemiologic Research Program at Aichi Cancer Center II), including both lifestyle and polymorphism data, following HERPACC-I which solely concentrated on lifestyle data. As of April 2001, about 3000 samples of DNA are being stored to conduct case-control studies. Genotyping of 46 polymorphisms has been conducted at the laboratory of the Division of Epidemiology and Prevention. Twelve case-control studies and two papers on a new PCR method, PCR-CTPP (polymerase chain reaction with confronting two-pair primers), have been accepted for publication. Significant findings in Japanese were found for 1) gene-environment interaction for esophageal cancer between heavy drinking and aldehyde dehydrogenase 2 (ALDH2), 2) malignant lymphoma risk with methylenetetrahydrofalate reductase (MTHFR) and methionine synthase (MS), 3) interactions between smoking and two polymorphisms, interleukin 1B (IL-1B) and myeloperoxidase (MPO) for Helicobacter pylori infection, and 4) smoking habits with dopamine receptor D2 (DRD2) and IL-1B. Further studies on interactions with polymorphisms will continue to be conducted for Japanese, using larger sizes of samples.
MicroRNA-10b (miR-10b) has been reported to play an important role in some types of cancer, but the effects and possible mechanisms of action of miR-10b in the metastasis of nasopharyngeal carcinoma cells (NPC) have not been explored. The aim of the present study was to investigate the function of miR-10b in nasopharyngeal carcinoma and to determine the molecular mechanisms underlying its action. The MTT assay was used to assess proliferation of CNE-2Z cells. Wound healing and transwell migration assays were applied to assess cell migration and invasion, while and expression of E-cadherin and MMP-9 were detected using Western blot analysis. Real-time PCR was employed to detect the expression of genes related to migration and invasion and the 2-??Ct method was used to calculate the degree of expression. MTT assay showed the expression of miR-10b to have no effect on the proliferation of NPC cell lines. The wound healing assay showed that miR-10b mimics promoted the mobility and invasion of NPC cell lines. Inhibitors of miR-10b reduced the ability of NPC cell lines to migrate and invade. In addition, the expression of genes related to migration and invasion, such as E-cadherin, vimentin, and MMP-9, were confirmed to be different in the CNE-2Z NPC cell line transfected with miR-10b mimics and with miR-10b inhibitors. In the present study, miR-10b was found to upregulate the expression of MMP-9 and knockdown of miR-10b was found to significantly downregulate the expression of E-cadherin. On the whole, these results showed that miR-10b plays an important role in the invasion and metastasis of NPC cells.
Loss of heterozygosity (LOH) on chromosomal regions is crucial in tumor progression and this study aimed to identify genome-wide LOH in pancreatic cancer. Single-nucleotide polymorphism (SNP) profiling data GSE32682 of human pancreatic samples snap-frozen during surgery were downloaded from Gene Expression Omnibus database. Genotype console software was used to perform data processing. Candidate genes with LOH were screened based on the genotype calls, SNP loci of LOH and dbSNP database. Gene annotation was performed to identify the functions of candidate genes using NCBI (the National Center for Biotechnology Information) database, followed by Gene Ontology, INTERPRO, PFAM and SMART annotation and UCSC Genome Browser track to the unannotated genes using DAVID (the Database for Annotation, Visualization and Integration Discovery). The candidate genes with LOH identified in this study were MCU, MICU1 and OIT3 on chromosome 10. MCU was found to encode a calcium transporter and MICU1 could encode an essential regulator of mitochondrial Ca2+ uptake. OIT3 possibly correlated with calcium binding revealed by the annotation analyses and was regulated by a large number of transcription factors including STAT, SOX9, CREB, NF-kB, PPARG and p53. Global genomic analysis of SNPs identified MICU1, MCU and OIT3 with LOH on chromosome 10, implying involvement of these genes in progression of pancreatic cancer.
Data from a recent genome-wide association studiesy of gastric cancer (GC) and oesophageal squamous cell carcinoma in Chinese living in the Taihang Mountains of north-central China suggest that 1q22 and 10q23 are susceptibility-associated regions for GC. However, this has not been confirmed in southern Chinese populations. The aim of this study was to investigate whether these polymorphisms at 1q22 and 10q23 are associated with the risk of GC in a southern Chinese population. We selected seven top significant associated single nucleotide polymorphisms (SNPs) at 1q22 and 10q23 and conducted a population-based case- control study in a southern Chinese population. Genotypes were determined using MassARRAYTM system (Sequenome, San Diego, CA). Two SNPs at 1q22, rs4072037 and rs4460629, were significantly associated with a reduced risk of GC, best fitting the dominant genetic model. Logistic regression models adjusted for age and sex showed that rs4072037 AG and GG (OR=0.64, P=0.017, compared with AA) and rs4460629 CT and TT (OR=0.54, P=0.0016, compared with TT) significantly reduced the risk of GC. However, no significant results for the five SNPs at 10q23 were obtained in this study. These outcomes indicate that 1q22 is associated with GC susceptibility in this southern Chinese population, while an association for the locus at 10q23 was not confirmed.
Association of PNLIPRP3 Overexpression and Clinicopathological Data on 22 HCCs 
Multivariate Analysis of Prognostic Factors for Survival in HCC Patients by Cox Regression 
Our previous study of gene alterations in 29 hepatocellular carcinoma (HCC) using AP-PCR amplified with 59 different 10-mer arbitrary primers and gene cloning, indicated DNA alterations by DNA fingerprints from 34 primers. Among these, the altered DNA fragment from primer U-8 predominated (62%). The aim of this report is to identify the gene alterations on chromosomal banding and gene expression in these patients, including the association of these alterations with patient demographic data. Seven different sequences, mapped to chromosomes 5q33.3, 7q31.33, 7q34, 9p24.3, 10q25.3, 13q31.3, and 16p11.2, were identified by gene cloning and nucleotide sequencing. Novel PNLIPRP3 gene over-expression and DOCK8 gene under-expression were observed in 41% and 44% of these patients, respectively, which point to an association of these genes and the development of HCC. Likewise, allelic loss on chromosome 10q25.3 was associated with shorter survival among HCC patients (P=0.03); this indicated that allelic loss on chromosome 10q25.3 may serve as a prognostic marker in patients with HCC.
Multi-item Summative Scales used to Measure Psychosocial Risk Factors, Delhi and Chennai 
In 2004, baseline surveys of Project MYTRI, a randomized intervention trial in Chennai and Delhi, India, found that tobacco use among 6th graders was greater than that among 8th graders. These results were surprising - typically, tobacco use increases with grade level. The present study aimed to assess whether this unique differential was sustained over time, as students moved into higher grades. Self-reported data from a sample of youth (n=3,404) present at three annual surveys (2004, 2005, 2006) were analyzed. Mixed-effects regression models were used to compare prevalence of lifetime tobacco use and nine psychosocial risk factor scales between two student cohorts, 6th grade (or younger) cohort and 8th grade (or older) cohort. Stratified analyses were also conducted by gender, age, city and school type. From 2004 to 2006, the 6th grade (or younger) cohort of students reported higher rates of lifetime tobacco use, and these differences were maintained over two years, even when the study sample was stratified by gender, age, city and school type. Similarly, students in the 6th grade (or younger) cohort scored greater risk for tobacco use on all psychosocial risk factors analyzed here. Tobacco use was found to be problematic among students in two Indian cities, particularly so for those in younger grades. Projections of health impact due to tobacco may be larger than anticipated if these adolescents continue to use tobacco as young adults. Further epidemiologic research and interventions to curb tobacco use among young(er) adolescents are warranted.
The Peutz-Jeghers syndrome (PJS) is characterized by hamartomatous polyposis of the gastro-intestinal (GI) tract, with mucocutaneous pigmentation. We have experienced a case of a 10-year-old girl who presented with PJS, intussusception, colonic perforation and colonic adenocarcinoma. Finally, this case developed airway obstruction from the mediastinal mass. In order to prevent cancer and short bowel syndrome, aggressive screening is recommended.
Background: Pereskia sacharosa is a genus of cacti widely used in folk medicine for cancer-related treatment. Anti-proliferative effects have been studied in recent years against colon, breast, cervical and lung cancer cell lines, with promising results. We here extended study of anti-proliferative effects to a blood malignancy, leukemia. Materials and methods: Two leukemic cell lines, MV4-11 (acute myeloid leukemia) and K562 (chronic myeloid leukemia), were studied. IC50 concentrations were determined and apoptosis and cell cycle regulation were studied by flow cytometric analysis. The expression of apoptosis and cell-cycle related regulatory proteins was assessed by Western blotting. Results: P sacharosa inhibited growth of MV4-11 and K562 cells in a dose-dependent manner. The mode of cell death was via induction of intrinsic apoptotic pathways and cell cycle arrest. There was profound up-regulation of cytochrome c, caspases, p21 and p53 expression and repression of Akt and Bcl-2 expression in treated cells. Conclusions: These results suggest that P sacharosa induces leukemic cell death via apoptosis induction and changes in cell cycle checkpoint, thus deserves further study for anti-leukemic potential.
Demographic Characteristics 
The prevalence of human papillomavirus genotypes differs in various target organs. HPV16 is the most prevalent genotype in the cervix while genotypes 6 and 11 are highly prevalent in skin and aero-digestive tract infections. In this study HPV11 positive specimens were selected from cervix, larynx and lung biopsy tissue to analyze the whole genome by PCR and direct sequencing. Five HPV11 whole genomes were characterized, consisting of two cervical specimens, two laryngeal specimens and one lung specimen. The results showed high homology of HPV11 in these organs. Phylogenetic analysis showed that all HPV11 derived from various organs belonged to the same lineage. Molecular characterization and functional studies can further our understanding of virulence, expression or transmission. Additional studies on functional protein expression at different organ sites will also contribute to our knowledge of HPV infection in various organs.
The C609T single nucleotide polymorphism of the NAD(P)H:quinone oxidoreductase 1 (NQO1) gene has been identified as an important risk parameter for the susceptibility to colorectal cancer. We here carried out a case-control study and examined the genotype distribution of NQO1 C609T (Pro189Ser) using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) approach, to investigate the possible role of this SNP as a risk factor in colorectal cancer development in Kasmir, India. We investigated the genotype distribution in 86 CRC cases in comparison with 160 healthy subjects and also focused on clinicopathological variables in the CRC cases. The observed genotype frequencies in cases and controls were significantly different [OR=1.64; 95%CI=0.94-2.86]. We also found a significant association between the Ser/Ser variant form with age group, smoking status, tumor location, nodal status/ higher tumor grade and with exposure to pesticides. Therefore, we suggest that the NQO1 C609T SNP is involved either in susceptibility or development of CRC in the ethnic Kashmiri population.
Immunohistochemical Staining for MMP-11 in Prostate Adenocarcinoma Tissues. Positive label was found in cytoplasm of stromal cells, and normal prostate tissue. (A) Normal prostate tissue is MMP-11 negative. The expression of MMP-11 was classified as low level (B-D) and high level (E-F) according to the staining intensity and frequency score (Original magnification x200) 
Background: The incidence of prostate cancer, one of the most common cancers in elderly men, is increasing annually in Thailand. Matrix metalloproteinase 11 (MMP-11) is a member of the extracellular matrix metalloproteases which has been associated with human tumor progression and clinical outcome. Aim: To quantify MMP-11 expression in prostatic adenocarcinoma tissues and to determine whether its overexpression correlates with survival outcome, and to assess its potential as a new prognostic marker. Materials and methods: Expression of MMP-11 was analyzed using immunohistochemistry in 103 Thai patients with prostatic adenocarcinoma. Overall survival was analyzed using Kaplan-Meier methods and Cox regression models. Results: Immunoreactivity of MMP-11 was seen in the stroma of prostatic adenocarcinoma tissue samples, high expression being significantly correlated with poor differentiation in Gleason grading, pathologic tumor stage 4 (pT4), and positive-bone metastasis (p<0.05), but not age and prostatic-specific antigen (PSA) level. Patients with high levels of MMP-11 expression demonstrated significantly shorter survival (p<0.001) when compared to those with low levels. Multivariate analysis showed that MMP-11 expression and pT stage were related with survival in prostatic adenocarcinoma [hazard ratio (HR)=0.448, 95% confidence interval (95%CI)=0.212-0.946, HR=0.333, 95%CI=0.15-0.74, respectively]. Conclusions: Expression of MMP-11 is significantly associated with survival in prostatic adenocarcinoma. High levels may potentially be used for prediction of a poor prognosis.
Patient Characteristics (n=152)
DNA polymerase beta (polβ ) is a key enzyme in the base excision repair pathway. It is 39 kDa protein, with two subunits, one large subunit of 31 kDa having catalytic activity between exon V to exon XIV, and an 8 kDa smaller subunit having single strand DNA binding activity. Exons V to VII have double strand DNA binding activity, whereas exons VIII to XI account for the nucleotidyl transferase activity and exons XII to XIV the dNTP selection activity. To examine the association between polβ polymorphisms and the risk of ovarian cancer, the present case control study was performed using 152 cancer samples and non-metastatic normal samples from the same patients. In this study, mutational analysis of polβ genomic DNA was undertaken using primers from exons IX to XIV - the portion having catalytic activity. We detected alteration in DNA polymerase beta by SSCP. Two specific heterozygous point mutations of polβ were identified in Exon 9:486, A->C (polymorphism 1; 11.18%) and in Exon 11:676, A->C (polymorphism 2; 9.86%). The correlation study involving polymorphism 1 and 4 types of tissue showed a significant correlation between mucinous type with a Pearson correlation value of 4.03 (p=0.04). The association among polymorphism 2 with serous type and stage IV together have shown Pearson χ2 value of 3.28 with likelihood ratio of 4.4 (p=0.07) with OR =2.08 (0.3- 14.55). This indicates that there is a tendency of correlation among polymorphism 2, serous type and stage IV, indicating a risk factor for ovarian cancer. Hence, the results indicate that there is a tendency for polβ polymorphisms being a risk factor for ovarian carcinogenesis in India.
Endemic goitre is a major concern in many nations including Malaysia. Seven states in the country have been identified by Ministry of Health of Malaysia to have high incidence of goitre and one of these is Kelantan. This is a retrospective study over an 11-year period from 1994 to 2004 on all thyroid specimens submitted to the Pathology Department, Hospital Universiti Sains Malaysia (HUSM), in Kelantan. Epidemiological data were retrieved from the patients' records and pathology findings from the pathology reports. During this period, Department of Pathology HUSM received a total of 1,486 thyroid specimens. The female to male ratio was 6:1 and the median age was 40.0 years. The duration of goitre ranged from one to 15 years. Histopathological examination showed 71.9 percent were non-neoplastic and 28.1 percent neoplastic lesions. The hospital-based incidence of nodular hyperplasia was 9.9 per 100,000 admitted patients per year. The hospital-based incidence of all types of malignant thyroid cancers was 3.5 per 100,000. The most common malignancy was papillary carcinoma 76.6 percent. The majority of the cancers (59.5 percent) occurred in a background of nodular hyperplasia. Thyroid cancers made up 4.9 percent of all cancers seen in HUSM. This study suggests that malignant thyroid lesions arising from multi-nodular goitre are high in a population living in an iodine-deficiency area.
NAD(P)H: quinone oxidoreductase 1 (NQO1) is a cytosolic flavoprotein that catalyzes the two- electron reduction of quinoid compounds into hydroquinones. A single base substitution (C?T) polymorphism at 609 in the NQO1 gene reduces quinone reductase activity. Published data on the association between NQO1 C609T polymorphism and lung cancer risk are conflicting. To derive a more precise estimation of the relationship, a meta-analysis was performed. A total of 23 studies including 5,575 cases and 9,132 controls were assessed. The pooled result showed that the NQO1 polymorphism was not associated with a clear increased risk of lung cancer (OR = 1.009, 95% CI: 0.943-1.078; P heterogeneity=0.049). In the subgroup analysis by ethnicity, no clear increased risk was found among Asians for TT/CT versus CC (OR = 1.005; 95% CI = 0.890-1.135; P heterogeneity=0.024). However, the TT and CT genotypes combined were associated with significantly increased risk of lung cancer in Chinese (OR = 1.237, 95% CI: 1.029-1.486; P heterogeneity=0.061) among whom the variant allele is common. The variant genotype of NQO1 was also associated with modestly increased risk of lung cancer among white populations (OR = 1.017, 95% CI: 0.936-1.105; P heterogeneity=0.101). However, no significant association was found in Africans with all genetic models. Our meta-analysis suggests that the variant NQO1 C609T genotype may affect individual susceptibility to lung cancer. This meta- analysis suggests that the NQO1 609T allele is a low penetrant risk factor for developing lung cancer in Chinese.
Distribution, Crude and Adjusted Odds Ratio and Related 95% Confidence Intervals of Studied Variables Investigated in Study
The incidence rate of breast cancer in developed countries is almost three-fold higher than in developing countries. Iran has had one of the lowest incidence rates for breast cancer in the world, but during the recent decades a marked increase has been seen. The purpose of this study was to investigate some established risk factors of breast cancer in Iranian women. A study of 11,850 women participating in abreast screening program was conducted. The 197 women diagnosed with breast cancer and 11,653 healthy women were compared. Logistic regression was performed to investigate associations of reproductive and anthropometric factors with breast cancer risk. Family history of breast cancer (OR=1.94 , 95%CI=1.35-2.78), occupation (OR= 1.65,95%CI=1.20- 2.25), education level (OR=0.50,95%CI=0.28-0.91), parity (OR=0.27, 95%CI=0.12-0.59), menopausal status (OR=3.15, 95%CI=2.35-4.21), age at menarche (OR=0.33, 95%CI=0.15-0.70), and age at the first pregnancy (OR=4.10 , 95%CI=1.13-14.77) were related to the risk of breast cancer. Decrease in parity may to some extent explain the rising trend of incidence of breast cancer incidence in Iranian women.
Pedigree, DHPLC trace and Sequencing data in the patients with deleterious mutation. 1A: Pedigree chart, DHPLC trace and DNA Sequencing data from the patient with the 5 base pair deletion in Exon 12 of BRCA1; 1B: Pedigree chart, DHPLC trace and DNA Sequencing data from the patient with the 5 base pair deletion in Exon 11O of BRCA2; 1C: Pedigree chart, DHPLC trace and DNA Sequencing data from the patient with the point mutation CGAAETGA in Exon 13 of BRCA1.  
BRCA1 & BRCA2 Status in Patients Studied (Only Mutations & Polymorphisms in the Coding Region Shown)
Cancer of the breast is the second most common cancer seen among Indian women. This study describes the use of DHPLC for mutation analysis for BRCA1, BRCA2 and CHEK2 (1100delC) in 22 patients with a family history of breast and/or ovarian cancer and early onset breast cancer (<35 years of age). Three of the 22 patients were found to have a non-sense mutation or a deletion, resulting in a premature stop codon, potentially leading to a truncated protein. Two of these were in BRCA1 (one was a novel 5 base deletion) and one in the BRCA2 gene. No patient was found in our series to have the CHEK2 (1100delC) mutation. DNA from a healthy blood donor and all but one of the 22 patients, demonstrated polymorphisms in BRCA1 and/or BRCA2 genes. This is the first study from South India, on BRCA1, BRCA2 & CHEK2 (1100 del C) mutations in patients with a family history of breast and/or ovarian cancer and early onset breast/ovarian cancer, using the sensitive DHPLC approach.
Links between the CHEK2 1100delC heterozygote and breast cancer risk have been extensively explored. However, both positive and negative associations with this variant have been reported in individual studies. For a detailed assessment of the CHEK2 1100delC heterozygote and breast cancer risk, relevant studies published as recently as May 2012 were identified using PUBMED and EMBASE and selected using a priori defined criteria. The strength of the relationship between the CHEK2 1100delC variant and breast cancer risks was assessed by odds ratios (ORs) under the fixed effects model. A total of 29,154 cases and 37,064 controls from 25 case-control studies were identified in this meta-analysis. The CHEK2 1100delC heterozygote was more frequently detected in cases than in controls (1.34% versus 0.44%). A significant association was found between CHEK2 1100delC heterozygote and breast cancer risk (OR=2.75, 95% CI: [2.25, 3.36]). The ORs and CIs were 2.33 (95% CI: [1.79, 3.05]), 3.72 (95% CI: [2.61, 5.31]) and 2.78 (95% CI: [2.28, 3.39]) respectively in unselected, family, early-onset breast cancer subgroups. The CHEK2 1100delC variant could be a potential factor for increased breast cancer risk in Caucasians. However, more consideration is needed in order to apply it to allele screening or other clinical work.
The purpose of this study was to analyze the clinical presentation, histopathology and complications following parotid surgery. We retrospectively reviewed the charts of 112 patients who underwent parotidectomy from January 2000 to February 2010. Data including age, sex, clinical signs and symptoms, histology and complication were collected from medical records. Of the total, 82 (74%) had benign lesions, 30 (36%) had malignant tumors. The most common benign tumor was pleomorphic adenoma (57%), and the most common malignant tumor was mucoepidermoid carcinoma (16%). Analysis of the correlation between fine-needle aspiration cytology and final histology revealed that fine-needle aspiration sensitivity, specificity and accuracy to 86.6%, 97.6% and 94.6% respectively. The most common complication following parotidectomy was transient facial nerve palsy (18.7%). Superficial parotidectomy is associated with a decrease incidence of transient facial nerve dysfunction compared with that of total parotidectomy. High grade or advanced tumour is a predictor of poor outcome which may require adjuvant therapy.
A monosomal karyotype (MK), defined as ≥2 autosomal monosomies or a single monosomy in the presence of additional structural abnormalities, was recently identified as an independent prognostic factor conveying an extremely poor prognosis in patients with acute myeloid leukemia (AML). In the present study, after excluding patients with t(15;17), t(8;21), inv(16) and normal karyotypes, 324 AML patients with cytogenetic abnormalities were the main subject of analysis. The incidences of MK were 13% in patients aged 15 to 60 years and 18% in those between 15 and 88 years old. MK was much more prevalent among elderly patients (p < 0.001) and was significantly associated with the presence of -7, -5, del(5q), abn12p, abn17p, -18 or 18q-, -20 or 20q- and CK (for all p <0.001 except for abn12p p=0.009), and +8 or +8q was less frequent in MK+ AML(p=0.007). No correlation was noted between monosomal karyotype and FAB subtype (p > 0.05); MK remained significantly associated with worse overall survival among patients with complex karyotype (p= 0.032); A single autosomal monosomy contributed an additional negative effect in OS of patients with structural cytogenetic abnormalities (P=0.008). This report presents the prevalence, feature and prognostic impact of MK among a large series of Chinese AML patients from a single center for the first time.
To evaluate the safety and efficacy of combined chemoradiotherapy or radiotherapy alone in elderly patients with esophageal carcinoma to identify the best method of treatment. One hundred and sixteen patients with esophageal carcinoma aged 70 and older who received definitive radiotherapy or chemoradiotherapy entered the study. Overall survival (OS), disease-free survival (DFS) and treatment- related toxicities were assessed. The median OS of the overall population was 17.9 months. For patients treated with cCRT, sCRT and radiotherapy alone, the median OS was 22.3 months, 18.0 months and 12.4 months respectively(P=0.044). Median OS for patients treated with radiotherapy dose ≥60Gy and <60Gy was 20.2 months and 10.9 months respectively (p=0.017). By univariate analysis, Chemoradiotherapy (include cCRT and sCRT) and radiotherapy dose ≥60Gy were found to achieve higher survival rates compared with radiotherapy alone and radiotherapy dose <60Gy (P=0.015, P=0.017). By multivariate analysis, chemoradiotherapy (HR=1.645, P=0.022) and radiotherapy dose ≥60Gy (HR=1.642, P=0.025) were identified as independent prognostic factors of OS. Definitive concurrent chemoradiotherapy could be considered as a feasible and effective treatment in esophageal carcinoma patients aged 70 and older. Radiotherapy dose 60Gy is an effective treatment option compared with standard dose radiotherapy, while higher doses are not beneficial to improve survival.
The Chemical Structure of Benzimidazole 5.
Benzimidazoles 1-4 were obtained using modified synthesis methods and studied for their ability to inhibit cell proliferation of colon cancer cell HCT-116 and breast cancer cell MCF-7 using MTT assays. In the HCT-116 cell line, benzimidazole 2 was found to have an IC50 value of 16.2±3.85 μg/mL and benzimidazole 1 a value of 28.5±2.91 μg/mL, while that for benzimidazole 4 was 24.08±0.31 μg/mL. In the MCF-7 cell line, benzimidazole 4 had an IC50 value of 8.86±1.10 μg/mL, benzimidazole 2 a value of 30.29±6.39 μg/mL, and benzimidazole 1 a value of 31.2±4.49 μg/mL. Benzimidazole 3 exerted no cytotoxity in either of the cell lines, with IC50 values >50 μg/mL. The results suggest that benzimidazoles derivatives may have chemotherapeutic potential for treatment of both colon and breast cancers.
Top-cited authors
xin-en Huang
  • Nanjing Medical University
Malcolm Anthony Moore
  • Asian Pacific Press
Kazuo Tajima
  • Mie University
Hamid Salehiniya
  • Birjand University of Medical Sciences
Mahshid Ghoncheh
  • Hamadan University of Medical Sciences