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Wei-Hua Jia,
Ben Zhang,
Keitaro Matsuo, Aesun Shin,
Yong-Bing Xiang,
Sun Ha Jee,
Dong-Hyun Kim,
Zefang Ren,
Qiuyin Cai,
Jirong Long, [......],
Hong-Lan Li,
Ji Won Park,
Jaeseong Jo,
Jin-Young Jeong,
Satoyo Hosono,
Graham Casey,
Ulrike Peters,
Xiao-Ou Shu,
Yi-Xin Zeng,
Wei Zheng
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ABSTRACT: To clarify the trend in colorectal cancer mortality in Asian countries. We analyzed the colorectal cancer mortality in four Asian countries using the World Health Organization mortality database and the Korea National Statistics Office database. The annual age-standardized rates and truncated rated for the three age groups (30-49, 50-69 and ≥ 70 years) for Hong Kong of China (1969-2009), Japan (1955-2009), South Korea (1985-2006), and Singapore (1966-2009) were estimated. A joinpoint regression model was used to detect significant trends in mortality rates. Colorectal cancer mortality in men started to decrease in 1992 in Japan followed by Singapore and Hong Kong of China in 1995. The mortality rates in women stared to decrease in 1980 in Singapore, followed by Hong Kong of China and Japan in 1996. In all countries and both genders, except for women in Singapore, the decrease in mortality began in the younger age groups. The colorectal cancer mortality in the four studied Asian countries has started to decrease, and the decrease occurred first in the younger age groups.
World Journal of Gastroenterology 02/2013; 19(7):979-83. · 2.47 Impact Factor
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ABSTRACT: The current study aimed to assess the effect of dietary calcium intake and possible interactions with calcium-sensing receptor (CASR) gene polymorphisms on colorectal cancer risk.
A total of 420 colorectal cancer cases and 815 controls were included in the analysis. Calcium intake was investigated using a 103 item semi-quantitative food frequency questionnaire, and four single nucleotide polymorphisms (SNPs) within the CASR, rs10934578, rs12485716, rs2270916, and rs4678174, were evaluated.
No SNPs were associated with colorectal cancer risk after adjusting for covariates. Overall, no significant effect modification by CASR polymorphisms on the association between calcium intake and colorectal cancer risk were detected. However, all 4 of the polymorphisms within the CASR showed significantly higher odds ratios for association with colorectal cancer risk in the low-calcium-intake group compared to the high-calcium-intake group. In the case of rs2270916, individuals with the CC genotype and low calcium intake showed an increased colorectal cancer risk compared to their counterparts with the TT genotype and high calcium intake (OR = 2.11, 95% CI = 1.27-3.51).
Subjects with lower calcium intake exhibited a higher colorectal cancer risk compared with subjects with the same genotype who had higher calcium intake. Our results suggest that individuals who have low dietary calcium intake should be aware of their increased colorectal cancer risk and prevention strategies.
PLoS ONE 01/2013; 8(3):e59628. · 4.09 Impact Factor
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Wei-Hua Jia,
Ben Zhang,
Keitaro Matsuo, Aesun Shin,
Yong-Bing Xiang,
Sun Ha Jee,
Dong-Hyun Kim,
Zefang Ren,
Qiuyin Cai,
Jirong Long, [......],
Hong-Lan Li,
Ji Won Park,
Jaeseong Jo,
Jin-Young Jeong,
Satoyo Hosono,
Graham Casey,
Ulrike Peters,
Xiao-Ou Shu,
Yi-Xin Zeng,
Wei Zheng
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ABSTRACT: To identify new genetic factors for colorectal cancer (CRC), we conducted a genome-wide association study in east Asians. By analyzing genome-wide data in 2,098 cases and 5,749 controls, we selected 64 promising SNPs for replication in an independent set of samples, including up to 5,358 cases and 5,922 controls. We identified four SNPs with association P values of 8.58 × 10(-7) to 3.77 × 10(-10) in the combined analysis of all east Asian samples. Three of the four were replicated in a study conducted in 26,060 individuals of European descent, with combined P values of 1.22 × 10(-10) for rs647161 (5q31.1), 6.64 × 10(-9) for rs2423279 (20p12.3) and 3.06 × 10(-8) for rs10774214 (12p13.32 near the CCND2 gene), derived from meta-analysis of data from both east Asian and European-ancestry populations. This study identified three new CRC susceptibility loci and provides additional insight into the genetics and biology of CRC.
Nature Genetics 12/2012; · 35.53 Impact Factor
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ABSTRACT: This study was conducted in order to demonstrate changing trends in colorectal cancer incidence according to sex, age group, and anatomical location in the Korean population.
Data from the Korea Central Cancer Registry between 1999 and 2009 were analyzed. Annual percent changes (APCs) of sex- and age-specific incidence rates for cancer of the proximal colon (International Statistical Classification of Diseases and Related Health Problems, 10th revision [ICD-10] code C18.0-18.5), distal colon (C18.6-18.7), and rectum (C19-20), and male-to-female incidence rate ratios (IRR) were calculated.
The age-standardized incidence rate (ASR) of colorectal cancer was 27 (per 100,000) in 1999 and increased to 50.2 in 2009 among men (APC, 6.6%). The ASR for women was 17.2 in 1999 and 26.9 in 2009 (APC, 5.1%). The rectum was the most common site of cancer among both men and women during 1999 and 2009. However, the distal colon had the highest APC (10.8% among men and 8.4% among women), followed by the proximal colon (7.9% among men and 6.6% among women), and rectum (5.2% among men and 2.4% among women). The proportion of rectal cancer decreased from 51.5% in 1999 to 47.1% in 2009 among men, and from 50.5% to 42.8% among women. An increase in the male-to-female IRR was observed for distal colon cancer and rectal cancer, whereas the IRR for proximal colon cancer was stable.
The rapid increase in colorectal cancer incidence is mainly attributed to the increase in colon cancer, especially distal colon cancer, and may be explained by a transition of risk factors for subsites or by the effect of colorectal cancer screening.
Cancer Research and Treatment 12/2012; 44(4):219-26.
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Jae Jeong Yang,
Lisa Y Cho,
Kwang-Pil Ko,
Seung Hyun Ma, Aesun Shin,
Bo Youl Choi,
Dong Soo Han,
Kyu Sang Song,
Yong Sung Kim,
Soung-Hoon Chang,
Hai-Rim Shin,
Daehee Kang,
Keun-Young Yoo,
Sue K Park
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ABSTRACT: To investigate whether genes involved in AKT/nuclear factor kappa B signaling and/or gene-environment interactions between the genes and phytoestrogens may be susceptible factors for gastric cancer.
The representative single nucleotide polymorphisms (SNPs) identified during the primary analysis (screening a total of 622 SNPs within ± 5 kbp of the 51 target gene locations) were further investigated in 317 matched case-control sets. The summary odds ratios (ORs) and 95% confidence intervals (CIs) for gastric cancer were calculated. Interaction effects between the SNPs and phytoestrogen biomarkers (genistein, daidzein, equol, and enterolactone) were computed. CDK1 rs4145643, FAS rs6586161, and FAS rs1468063 in the AKT signaling pathway presented significant genetic effects on gastric cancer (OR = 0.81 (95% CI: 0.66-0.99) for CDK1 rs4145643; OR = 1.27 (95% CI: 1.03-1.58) for FAS rs6586161; OR = 1.29 (95% CI: 1.03-1.56) for FAS rs1468063; Cochran Q statistics > 0.10). Risk alleles of FAS rs6586161, FAS rs1468063, MAP3K1 rs16886448, and MAP3K1 rs252902 showed significant interaction effects with enterolactone (p(interaction) < 0.05).
CDK1 and FAS genes involved in AKT signaling and influenced by anti-carcinogenic property of phytoestrogens can play a role as susceptible genetic factors in gastric carcinogenesis. FAS and MAP3K1 genes significantly interact with enterolactone, thereby modifying the individual's risk for gastric cancer.
Molecular Nutrition & Food Research 10/2012; 56(11):1617-26. · 4.30 Impact Factor
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En-Joo Jung, Aesun Shin,
Sue K Park,
Seung-Hyun Ma,
In-Seong Cho,
Boyoung Park,
Eun-Ha Lee,
Soung-Hoon Chang,
Hai-Rim Shin,
Daehee Kang,
Keun-Young Yoo
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ABSTRACT: To examine the association between alcohol consumption habit, types of beverages, alcohol consumption quantity, and overall and cancer-specific mortality among Korean adults.
The alcohol consumption information of a total of 16 320 participants who were 20 years or older from the Korean Multi-center Cancer Cohort were analyzed to examine the association between alcohol consumption habit and mortality (median follow-up of 9.3 years). The Cox proportional hazard model was used to estimate the hazard ratio (HR) of alcohol consumption to mortality adjusting for age, sex, geographic areas, education, smoking status, and body mass index.
Alcohol drinkers showed an increased risk for total mortality compared with never drinkers (HR, 1.72; 95% confidence interval [CI], 1.38 to 2.14 for past drinkers; HR, 1.21; 95% CI, 1.06 to 1.39 for current drinkers), while past drinkers only were associated with higher risk for cancer deaths (HR, 1.84; 95% CI, 1.34 to 2.53). The quantity of alcohol consumed per week showed a J-shaped association with risk of mortality. Relative to light drinkers (0.01 to 90 g/wk), never drinkers and heavy drinkers (>504 g/wk) had an increased risk for all-cause and cancer deaths: (HR, 1.18; 95% CI, 0.96 to 1.45) and (HR, 1.39; 95% CI, 1.05 to 1.83) for all-cause mortality; and (HR, 1.55; 95% CI, 1.15 to 2.11) and (HR, 2.07; 95% CI, 1.39 to 3.09) for all cancer mortality, respectively. Heavy drinkers (>504 g/wk) showed an elevated risk for death from stomach and liver cancers.
The present study supports the existence of a J-shaped association between alcohol consumption quantity and the risk of all-cause and cancer deaths. Heavy drinkers had an increased risk of death from cancer overall and liver and stomach cancer.
Journal of preventive medicine and public health = Yebang Ŭihakhoe chi. 09/2012; 45(5):301-8.
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ABSTRACT: Gastric cancer is ranked as the most common cancer in Koreans. A recent molecular biological study about the folate pathway gene revealed the correlation with a couple of cancer types. In the folate pathway, several genes are involved, including methylenetetrahydrofolate reductase (MTHFR), methyltetrahydrofolate-homocysteine methyltransferase reductase (MTRR), and methyltetrahydrofolate-homocysteine methyltransferase (MTR). The MTHFR gene has been reported several times for the correlation with gastric cancer risk. However, the association of the MTRR or MTR gene has not been reported to date. In this study, we investigated the association between the single nucleotide polymorphisms (SNPs) of the MTHFR, MTRR, and MTR genes and the risk of gastric cancer in Koreans. To identify the genetic association with gastric cancer, we selected 17 SNPs sites in folate pathway-associated genes of MTHFR, MTR, and MTRR and tested in 1,261 gastric cancer patients and 375 healthy controls. By genotype analysis, estimating odds ratios and 95% confidence intervals (CI), rs1801394 in the MTRR gene showed increased risk for gastric cacner, with statistical significance both in the codominant model (odds ratio [OR], 1.39; 95% CI, 1.04 to 1.85) and dominant model (OR, 1.34; 95% CI, 1.02 to 1.75). Especially, in the obese group (body mass index ≥ 25 kg/m(2)), the codominant (OR, 9.08; 95% CI, 1.01 to 94.59) and recessive model (OR, 3.72; 95% CI, 0.92 to 16.59) showed dramatically increased risk (p < 0.05). In conclusion, rs1801394 in the MTRR gene is associated with gastric cancer risk, and its functional significance need to be validated.
Genomics & informatics. 09/2012; 10(3):184-93.
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ABSTRACT: Regular exercise and physical activity (PA) are known to be protective factors for maintaining bone mineral density (BMD) and preventing osteoporotic fracture. We investigated the associations between leisure-time PA and BMD in 2,903 premenopausal and 2,267 postmenopausal women in Korea. BMDs of the lumbar spine and femur were measured using dual-energy X-ray absorptiometry. Leisure-time PA levels were assessed by a self-administrated questionnaire, and a total metabolic equivalent (MET) score was obtained. Regardless of menopausal status, performing more than moderate levels of leisure-time PA or total MET score had a significant positive association with BMD at both the lumbar spine and femur. In the premenopausal group, women whose total MET score was 1,050-1,500 (MET-min/week) appeared to have the highest lumbar spine and femoral BMD (p < 0.001). The associations between PA level and lumbar spine and femoral BMD were also shown in the postmenopausal group (p < 0.001). In addition, we found dose-response relationships between increasing exercise level and femoral BMD in both the premenopausal and postmenopausal groups. Our results indicate that a more than moderate level of leisure-time PA plays a role in maintaining BMD.
Calcified Tissue International 07/2012; 91(3):178-85. · 2.38 Impact Factor
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ABSTRACT: Is there any effect of genetic polymorphisms in adiposity-related genes on the timing of menarche and menopause and the total duration of menstruation among Korean women? SUMMARY ANSWER: Our results suggest that the adiposity-related genes LEP, LEPR and PPARγ may play a role in the onset and cessation of menstruation, and the total duration of menstruation. WHAT IS KNOWN AND WHAT THIS PAPER ADDS: Previous candidate-gene approaches have mainly presented the results for genes related to the estrogen metabolism pathway. Most genes of interest that participate in steroid-hormone metabolism, such as estrogen receptor α and estrogen receptor β, have been associated with age at menarche and menopause. This study shows the possibility that adiposity-related genes also influence the duration of menstruation.
We recruited 400 breast cancer patients and 452 healthy participants from a case-control study at the Center for Breast Cancer, National Cancer Center in Korea. Ten single nucleotide polymorphisms (SNPs) in the leptin (LEP), leptin receptor (LEPR) and peroxisome proliferator-activated receptor gamma (PPARγ) genes were investigated to evaluate their possible effects on menstruation. Associations between SNPs and age at menarche, age at menopause and duration of menstruation were evaluated.
Four SNPs (rs2167270 of LEP, rs7602 of LEPR and rs4684846 and rs3856806 of PPARγ) were associated with late menarche (≥ 17-year-old). Four SNPs (rs2167270 of LEP and rs1801282, rs2120825, and rs3856806 of PPARγ) were associated with early menopause (<40-year-old) among post-menopausal women. In logistic regression models with covariate adjustment, women with the GG genotype of rs7602 (LEPR) had a higher risk for late menarche [odds ratio (OR) = 1.83, 95% confidence interval (CI) = 1.01-3.31] compared with their counterparts carrying the GA or AA genotypes. In addition, the GG genotype of rs2167270 (LEP) was inversely associated with a duration of menstruation of <30 years (OR = 0.59, 95% CI = 0.31-1.00) compared with the GA or AA genotypes. BIAS, LIMITATIONS AND GENERALIZABILITY TO OTHER POPULATIONS: We obtained information on the age at menarche and menopause from self-administered questionnaires, and some participants might have had difficulty in remembering their age at menarche and menopause. However, this is a non-differential misclassification and should not appreciably affect the interpretation of the results of this study.
Human Reproduction 04/2012; 27(7):2193-200. · 4.47 Impact Factor
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ABSTRACT: ObjectiveTransforming growth factor β1 (TGF-β1) is a multifunctional cytokine that may play an important role in tumor development
and progression.
MethodsWe evaluated gene expression patterns of TGF-β1 and its receptors [transforming growth factor β type I receptor (TβR-I) and
transforming growth factor β type II receptor (TβR-II)] in tumor tissue from patients with breast cancer or with benign breast
diseases (BBD) and adjacent normal tissue from the patients with breast cancer. Included in the study were 527 breast cancer
patients and 213 BBD patients who participated in the Shanghai Breast Cancer Study.
ResultsThe expression levels of the TGF-β1, TβR-I and TβR-II genes in breast tissue were quantified using real-time PCR. TβR-II expression
in cancer tissue was decreased by over 50% as compared to either adjacent normal tissue from the same patients or benign tumor
tissue from BBD patients (p<0.001). TGF-β1 expression was lower by approximately 20% in cancer tissue compared to adjacent
normal tissue (p=0.14) or to benign tumor tissue (p=0.002). Although TβR-I expression was also reduced in cancer tissue compared
to adjacent normal tissue, or benign tumor tissue, the magnitude of the reduction was less apparent than that for TβR-II.
Compared to patients with the lowest tertile value for TβR-II, patients with median tertile value for TβR-II had more favorable
overall survival (HR 0.47, 95% CI 0.27–0.85) and disease-free survival (HR 0.65, 95% CI 0.39–1.06). No apparent associations,
however, were observed between TGF-β1 or TβR-I expression and overall or disease-free survival.
ConclusionThe results from this study support the hypothesis that a decreased level of TβR-II gene expression, and thus reduced TGF-β1
sensitivity, is related to breast tumor progression.
Chinese Journal of Clinical Oncology 04/2012; 4(3):153-159.
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Byung Chang Kim, Aesun Shin,
Chang Won Hong,
Dae Kyung Sohn,
Kyung Su Han,
Kum Hei Ryu,
Bum Joon Park,
Ji Hyung Nam,
Ji Won Park,
Hee Jin Chang,
Hyo Seong Choi,
Jeongseon Kim,
Jae Hwan Oh
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ABSTRACT: Recently, some studies have shown that diabetes mellitus and metabolic syndrome increase the risk of colorectal neoplasms. Although the mechanism is not known, those have been proposed to contribute to this phenomenon, including insulin resistance, oxidative stress, and adipokine production. The objective of this study was to assess the association between metabolic risk factors and colorectal neoplasm.
Study participants visited the National Cancer Center, Korea, for screening (2007-2009). A total of 1,771 diagnosed adenoma patients and 4,667 polyp-free controls were included. The association between risk factors and colorectal neoplasm was evaluated using logistic regression models.
High waist circumference, blood pressure, and serum triglyceride levels were associated with an increased risk of colorectal adenoma. Metabolic syndrome (MS) was associated with an increased risk of adenoma (OR = 1.44, 95 % CI = 1.23-1.70). The association between MS and colorectal adenoma was observed regardless of advanced/low-risk adenoma, and multiplicity. MS affected right colon adenomas (OR = 1.50, 95 % CI = 1.22-1.85), left colon adenomas (OR = 1.36, 95 % CI = 1.05-1.76), and adenomas in multiple anatomical locations (OR = 1.59, 95 % CI = 1.19-2.12), but was not associated with rectum.
Central obesity, triglyceride level, and MS are risk factors for colorectal adenoma including advanced adenoma and multiplicity.
Cancer Causes and Control 03/2012; 23(5):727-35. · 2.88 Impact Factor
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ABSTRACT: Intake of high-glycemic index (GI) food has been postulated to reduce satiety, resulting in an increased total energy intake and reduced access to body fat as fuel. Thus, we hypothesize that high dietary GI and glycemic load (GL) are associated with an increased prevalence of obesity in the Korean population. Dietary GI and GL were calculated for 933 Korean men and women based on dietary intake assessed by food frequency questionnaires and using a GI table developed from published GI databases in a cross-sectional design. Mean differences in dietary GL and carbohydrate intake between obese and nonobese men were statistically significant after adjusting for covariates (P = .027 and .021, respectively). High dietary GL and carbohydrate intake were negatively associated with the prevalence of obesity among men in a multivariate-adjusted logistic regression model (P for trend = .026 and .036, respectively). Statistically significant effects of dietary GI and GL on the prevalence of obesity among women were observed in a generalized linear model (P = .002 and .042, respectively) and a logistic regression model (P for trend < .001 and = .007, respectively), after adjusting for covariates. Women with higher dietary GI and GL were more likely to be obese, a result consistent with our hypothesis. However, an inverse association for dietary GL and carbohydrate and prevalence of obesity was found in men, suggesting that mechanisms contributing to the prevalence of obesity between sexes may be different.
Nutrition research (New York, N.Y.) 03/2012; 32(3):153-9. · 1.20 Impact Factor
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Jeongseon Kim,
Young Ae Cho,
Il Ju Choi,
Yeon-Su Lee,
Sook-Young Kim, Aesun Shin,
Soo-Jeong Cho,
Myeong-Cherl Kook,
Ji Hyung Nam,
Keun Won Ryu,
Jun Ho Lee,
Young-Woo Kim
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ABSTRACT: Both variations in the interleukin-10 (IL10) gene and environmental factors are thought to influence inflammation and gastric carcinogenesis. Therefore, we investigated the associations between IL10 polymorphisms, Helicobacter pylori (H. pylori) infection, and smoking in noncardia gastric carcinogenesis in Koreans.
We genotyped three promoter polymorphisms (-1082A>G, -819T>C, and -592 A>C) of IL10 in a case-control study of 495 noncardia gastric cancer patients and 495 sex- and age-matched healthy controls. Multiple logistic regression models were used to detect the effects of IL10 polymorphisms, H. pylori infection, and smoking on the risk of gastric cancer, which was stratified by the histological type of gastric cancer.
The IL10-819C and -592C alleles were found to have complete linkage disequilibrium, and all three IL10 polymorphisms were associated with an increased risk of intestinal-type noncardia gastric cancer. These associations were observed only in H. pylori-positive subjects and current smokers. A statistically significant interaction between the IL10-592 genotype and H. pylori infection on the risk of intestinal-type gastric cancer was observed (P for interaction = 0.047). In addition, H. pylori-positive smokers who were carriers of either the IL10-1082G (OR [95% CI] = 17.76 [6.17-51.06]) or the -592C (OR [95% CI] = 8.37 [2.79-25.16]) allele had an increased risk of intestinal-type gastric cancer compared to H. pylori-negative nonsmokers homozygous for IL10-1082A and -592A, respectively. The interaction between the IL10-1082 polymorphism and the combined effects of H. pylori infection and smoking tended towards significance (P for interaction = 0.080).
Inflammation-related genetic variants may interact with H. pylori infection and smoking to increase the risk of noncardia gastric cancer, particularly the intestinal-type. These findings may be helpful in identifying individuals at an increased risk for developing noncardia gastric cancer.
PLoS ONE 01/2012; 7(1):e29643. · 4.09 Impact Factor
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ABSTRACT: Sex differences have been reported in the prognosis of certain cancers. In this study, we investigated whether Korean females display better survival rates compared with male patients for solid tumor sites.
We analyzed data from the Korean National Cancer Incidence Database from 599,288 adult patients diagnosed with solid cancers between 2005 and 2009. Patients were followed until December 2010. We applied a relative excess risk (RER) model adjusting for year of follow-up, age at diagnosis, and stage at diagnosis.
For all solid cancer sites combined, women displayed an 11% lower risk of death compared to men (RER 0.89; 95% CI 0.88-0.90) after adjusting for year of follow-up, age, stage, and case mix. Women showed significantly lower RERs for the following sites: head/neck, esophagus, small intestine, liver, nasal cavities, lung, bone/cartilages, melanoma of skin, soft tissue, brain and CNS, and thyroid. In contrast, women displayed a poorer prognosis than did men for colorectal, laryngeal, kidney and bladder cancer. However, the survival gaps between men and women narrowed by increase in age; female patients over 75 years of age displayed a 3% higher RER of death compared with males in this age group.
Female cancer patients display an improved survival for the majority of solid tumor sites, even after adjustment for age and stage. Age at diagnosis was the major contributor to the women's survival advantage.
PLoS ONE 01/2012; 7(12):e52457. · 4.09 Impact Factor
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ABSTRACT: Breast cancer is the second leading cancer in Korean women. To assess potential genetic associations between the prostate stem cell antigen (PSCA) gene in the chromosome 8q24 locus and breast cancer risk in Korean women, 13 SNPs were selected and associations with breast cancer risk were analyzed with reference to hormone receptor (HR) and menopausal status.
We analyzed DNA extracted from buffy coat from 456 patients and 461 control samples, using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) based upon region-specific PCR followed by allele- specific single base primer extension reactions. Risks associated with PSCA genotypes and haplotypes were estimated with chi-square test (χ2 -test), and polytomous logistic regression models using odds ratios (OR) and 95% confidence intervals (CIs), by HR and menopausal status.
In case-control analysis, odds ratios (OR) of rs2294009, rs2294008, rs2978981, rs2920298, rs2976395, and rs2976396 were statistically significant only among women with estrogen receptor (ER) negative cancers, and those of rs2294008, rs2978981, rs2294010, rs2920298, rs2976394, rs10216533, and rs2976396 were statistically significant only in pre-menopausal women, and not in postmenopausal women. Risk with the TTGGCAA haplotype was significantly elevated in ER (-) status (OR= 1.48, 95% CI= 1.03~2.12, p<0.05). Especially risk of allele T of rs2294008 is significantly low in pre-menopausal breast cancer patients and AA genotype of rs2976395 in ER (-) status represents the increase of OR value.
This report indicated for the first time that associations exist between PSCA SNPs and breast cancer susceptibility in Korean women, particularly those who are pre-menopausal with an estrogen receptor negative tumor status.
Asian Pacific journal of cancer prevention: APJCP 01/2012; 13(1):41-8. · 0.66 Impact Factor
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Lisa Y Cho,
Jae Jeong Yang,
Kwang-Pil Ko,
Seung Hyun Ma, Aesun Shin,
Bo Youl Choi,
Dong Soo Han,
Kyu Sang Song,
Yong Sung Kim,
Soung-Hoon Chang,
Hai-Rim Shin,
Daehee Kang,
Keun-Young Yoo,
Sue K Park
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ABSTRACT: The objective of the study was to investigate the role of genes (HSD3B1, CYP17A1, CYP19A1, HSD17B2, HSD17B1) involved in the steroid hormone biosynthesis pathway and progesterone receptor (PGR) in the etiology of gastric cancer in a population-based two-phase genetic association study.
In the discovery phase, 108 candidate SNPs in the steroid hormone biosynthesis pathway related genes and PGR were analyzed in 76 gastric cancer cases and 322 controls in the Korean Multi-Center Cancer Cohort. Statistically significant SNPs identified in the discovery phase were re-evaluated in an extended set of 386 cases and 348 controls. Pooled- and meta-analyses were conducted to summarize the results.
Of the 108 SNPs in steroid hormone biosynthesis pathway related genes and PGR analyzed in the discovery phase, 23 SNPs in PGR in the recessive model and 10 SNPs in CYP19A1 in the recessive or additive models were significantly associated with increased gastric cancer risk (p<0.05). The minor allele frequencies of the SNPs in both the discovery and extension phases were not statistically different. Pooled- and meta-analyses showed CYP19A1 rs1004982, rs16964228, and rs1902580 had an increased risk for gastric cancer (pooled OR [95% CI] = 1.22 [1.01-1.48], 1.31 [1.03-1.66], 3.03 [1.12-8.18], respectively). In contrast, all PGR SNPs were not statistically significantly associated with gastric cancer risk.
Our findings suggest CYP19A1 that codes aromatase may play an important role in the association of gastric cancer risk and be a genetic marker for gastric cancer susceptibility.
PLoS ONE 01/2012; 7(10):e47603. · 4.09 Impact Factor
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Jae Jeong Yang,
Lisa Y Cho,
Kwang-Pil Ko, Aesun Shin,
Seung Hyun Ma,
Bo Youl Choi,
Dong Soo Han,
Kyu Sang Song,
Yong Sung Kim,
Jong-Young Lee,
Bok Ghee Han,
Soung-Hoon Chang,
Hai-Rim Shin,
Daehee Kang,
Keun-Young Yoo,
Sue K Park
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ABSTRACT: To evaluate whether genes that encode CagA-interacting molecules (SRC, PTPN11, CRK, CRKL, CSK, c-MET and GRB2) are associated with gastric cancer risk and whether an interaction between these genes and phytoestrogens modify gastric cancer risk.
In the discovery phase, 137 candidate SNPs in seven genes were analyzed in 76 incident gastric cancer cases and 322 matched controls from the Korean Multi-Center Cancer Cohort. Five significant SNPs in three genes (SRC, c-MET and CRK) were re-evaluated in 386 cases and 348 controls in the extension phase. Odds ratios (ORs) for gastric cancer risk were estimated adjusted for age, smoking, H. pylori seropositivity and CagA strain positivity. Summarized ORs in the total study population (462 cases and 670 controls) were presented using pooled- and meta-analysis. Plasma concentrations of phytoestrogens (genistein, daidzein, equol and enterolactone) were measured using the time-resolved fluoroimmunoassay.
SRC rs6122566, rs6124914, c-MET rs41739, and CRK rs7208768 showed significant genetic effects for gastric cancer in both the pooled and meta-analysis without heterogeneity (pooled OR = 3.96 [95% CI 2.05-7.65], 1.24 [95% CI = 1.01-1.53], 1.19 [95% CI = 1.01-1.41], and 1.37 [95% CI = 1.15-1.62], respectively; meta OR = 4.59 [95% CI 2.74-7.70], 1.36 [95% CI = 1.09-1.70], 1.20 [95% CI = 1.00-1.44], and 1.32 [95% CI = 1.10-1.57], respectively). Risk allele of CRK rs7208768 had a significantly increased risk for gastric cancer at low phytoestrogen levels (p interaction<0.05).
Our findings suggest that SRC, c-MET and CRK play a key role in gastric carcinogenesis by modulating CagA signal transductions and interaction between CRK gene and phytoestrogens modify gastric cancer risk.
PLoS ONE 01/2012; 7(2):e31020. · 4.09 Impact Factor
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ABSTRACT: Genetic variants regulating the host immune system may contribute to the susceptibility for the development of gastric cancer. Little is known about the role of the innate immunity- and non-Hodgkin's lymphoma (NHL)-related genes for gastric cancer risk. This nested case-control study was conducted to identify candidate genes for gastric cancer risk for future studies.
In the Discovery phase, 3,072 SNPs in 203 innate immunity- and 264 NHL-related genes using the Illumine GoldenGateTM OPA Panel were analyzed in 42 matched case-control sets selected from the Korean Multi-center Cancer Cohort (KMCC). Six significant SNPs in four innate immunity (DEFA6, DEFB1, JAK3, and ACAA1) and 11 SNPs in nine NHL-related genes (INSL3, CHMP7, BCL2L11, TNFRSF8, RAD50, CASP7, CHUK, CD79B, and CLDN9) with a permutated p-value <0.01 were re-genotyped in the Replication phase among 386 cases and 348 controls. Odds ratios (ORs) for gastric cancer risk were estimated adjusting for age, smoking status, and H. pylori and CagA sero-positivity. Summarized ORs in the total study population (428 cases and 390 controls) are presented using pooled- and meta-analyses.
FOUR SNPS HAD NO HETEROGENEITY ACROSS THE PHASES: in the meta-analysis, DEFA6 rs13275170 and DEFB1 rs2738169 had both a 1.3-fold increased odds ratio (OR) for gastric cancer (95% CIs = 1.1-1.6; and 1.1-1.5, respectively). INSL3 rs10421916 and rs11088680 had both a 0.8-fold decreased OR for gastric cancer (95% CIs = 0.7-0.97; and 0.7-0.9, respectively).
Our findings suggest that certain variants in the innate immunity and NHL-related genes affect the gastric cancer risk, perhaps by modulating infection-inflammation-immunity mechanisms that remain to be defined.
PLoS ONE 01/2012; 7(9):e45274. · 4.09 Impact Factor
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ABSTRACT: To investigate the participation rates, positivity rates, and follow-up rates from 2004 to 2008 in an organized colorectal cancer (CRC) screening program using a fecal occult blood test (FOBT) in Korea.
The study population was men and women aged 50 years or older who were invited to participate in the National Cancer Screening Program for CRC between 1 January 2004 and 31 December 2008. We collected the FOBT results and follow-up information for the FOBT positives.
Participation rates increased steadily each year from 10.5% in 2004 to 21.1% in 2008. Between 2004 and 2008, FOBT positivity rates declined from 8.0% to 6.8%. Among the FOBT-positives, 61.3% of participants underwent either colonoscopy or double contrast barium enema (DCBE) in 2004, and this rate decreased to 38.6% in 2008. Age, health insurance type, and screening history were associated with adherence to follow-up test after a positive FOBT. With regard to follow-up tests, colonoscopy rates increased from 17.9% in 2004 to 27.6% in 2008, while DCBE decreased from 43.4% in 2004 to 11.0% in 2008. Colonoscopy was significantly more likely to be chosen as a follow-up test by men, participants aged 50-59 years, and National Health Insurance beneficiaries.
These findings suggest that targeting participants for follow-up, based on age and previous screening history, could be a good way to improve the follow-up rate.
Journal of Gastroenterology and Hepatology 10/2011; 27(6):1070-7. · 2.87 Impact Factor
