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ABSTRACT: To investigate the interrelationship of genetic polymorphisms in folate metabolic enzymes (MTHFRC677T, MTHFRA1298C, MTRA2756G and MTRRA66G) and their combinative effects with colorectal cancer (CRC).
A nested case-control study was designed and carried out. 140 CRC patients and 343 control subjects were included in this study. Polymorphisms of folate metabolic enzyme genes were genotyped by PCR-restriction fragment length polymorphism method. Risk of CRC was estimated by unconditional logistic model, and P value for interaction was calculated by likelihood test.
The allele of MTR2756G showed a positive association with CRC (OR = 2.04, 95% CI = 1.22 - 3.40). Those with MTHFR1298AA and MTR 2756AG/GG genotypes had an elevated risk with CRC (OR = 2.57, 95% CI, 1.42 -4.65), and their combinative effect showed a significant association with CRC (P = 0.04).
MTR2756G allele may be a risk factor of CRC, and interaction may exsit between polymorphisms of MTHFRA1298C and MTRA2756G. Further studies with larger sample and in different ethnic groups are needed.
Zhonghua zhong liu za zhi [Chinese journal of oncology] 07/2006; 28(6):429-32.
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ABSTRACT: To investigate the association between CYP1A1, GSTM1, T1, UGT1A7 polymorphisms and colorectal cancer risk.
A case-control study of 140 patients with cancers and 343 health controls was conducted to investigate the role of CYP1A1, GSTM1, T1, UGT1A7 polymorphisms in colorectal cancer. Gene-gene interactions among CYP1A1, GSTM1, T1, UGT1A7 polymorphisms were detected by case-control study and case-only study. Genotypes of four genes polymorphisms were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and unconditional logistic regression was adopted to analyze the data.
The CC, TC and CC genotypes of CYP1A1 T6235C significantly decreased the colorectal cancer risk as compared to TT genotype (OR = 0.493, 95% CI: 0.254-0.956, OR = 0.638, 95% CI: 0.427-0.952). GSTM1 and GSTT1 null genotype had no significant association with the increased risk of colorectal cancer while the mutant variants of UGT1A7 might increase the risk of colorectal cancer significantly (OR = 2.501, 95% CI: 1.456-4.296). The CORvalue for the gene-gene interactions between CYP1A1 variant and the null genotype of GSTT1, GSTM1-deleted and GSTT1-deleted genotype in the case-only design were 2.617 (95% CI: 1.015-6.752) and 3.935 (95% CI: 1.323-11.706), respectively. There was no significant interaction between CYP1A1 and GSTM1, CYP1A1 and UGT1A7.
This study suggests that CYP1A1 and UGT1A7 variants might be associated with colorectal cancer. CYP1A1 and GSTM1 might interact on GSTT1 to influence the risk of colorectal cancer.
Zhonghua yu fang yi xue za zhi [Chinese journal of preventive medicine] 02/2006; 40(1):13-7.
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ABSTRACT: To investigate the association between metabolic enzymes polymorphisms and the risk of colorectal cancer(CRC).
Methods of detection used were based on polymerase chain reaction(PCR) including PCR-restriction fragment length polymorphism (PCR-RFLP), allele specific-PCR (AS-PCR) and multiple-PCR to identify the polymorphisms of CYP1A1 6235T/C, CYP1A2 734C/A, CYP2E1 -1259G/C, CYP2E1 -1019C/T, GSTM1 and T1 null type, NAT1 and NAT2 alleles among 140 cases and 343 cancer-free controls.
The allele frequencies of CYP1A1 6235C, CYP1A2 734A, CYP2E1 -1259C, CYP2E1 -1019T, GSTM1 and T1 null type, NAT1* 10 and NAT2 Mx (x = 1,2,3) alleles were 31.65%, 63.77%, 23.02%, 32.61%, 57.25%, 17.39%, 26.45% and 39.21% in the case group and 39.85%, 66.62%, 20.27%, 28.61%, 55.46%, 20.35%, 25.22% and 39.36% in control group, respectively. The frequencies were in Hardy-Weinberg equilibrium. Data on single genetic polymorphism and stratification analysis of multi-genetic polymorphisms indicated that CYP1A1 6235CC homozygote was associated with the significant reduction of CRC risk (OR = 0.79, 95% CI: 0.63-0.99) and in individuals with CYP1A2 734A allele. CYP1A1 62345C allele had the same effect (OR = 0.53, 95% CI: 0.34-0.83). However, individuals with GSTT1 null genotype, GSTM1 null genotype could significantly increase the risk (OR = 4.41, 95% CI: 1.21-16.10).
CYP1A1 6235C allele might play an important role in fighting against colorectal carcinogenesis. However, GSTM1 and T1 null genotype might serve as risk factors genetically. Larger scale population-based studies were needed to confirm the current findings.
Zhonghua liu xing bing xue za zhi = Zhonghua liuxingbingxue zazhi 09/2005; 26(9):659-64.
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ABSTRACT: To set up a mathematic model for gastric cancer screening and to evaluate its function in mass screening for gastric cancer.
A case control study was carried on in 66 patients and 198 normal people, then the risk and protective factors of gastric cancer were determined, including heavy manual work, foods such as small yellow-fin tuna, dried small shrimps, squills, crabs, mothers suffering from gastric diseases, spouse alive, use of refrigerators and hot food, etc. According to some principles and methods of probability and fuzzy mathematics, a quantitative assessment model was established as follows: first, we selected some factors significant in statistics, and calculated weight coefficient for each one by two different methods; second, population space was divided into gastric cancer fuzzy subset and non gastric cancer fuzzy subset, then a mathematic model for each subset was established, we got a mathematic expression of attribute degree (AD).
Based on the data of 63 patients and 693 normal people, AD of each subject was calculated. Considering the sensitivity and specificity, the thresholds of AD values calculated were configured with 0.20 and 0.17, respectively. According to these thresholds, the sensitivity and specificity of the quantitative model were about 69% and 63%. Moreover, statistical test showed that the identification outcomes of these two different calculation methods were identical (P>0.05).
The validity of this method is satisfactory. It is convenient, feasible, economic and can be used to determine individual and population risks of gastric cancer.
World Journal of Gastroenterology 03/2005; 11(5):641-4. · 2.47 Impact Factor
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ABSTRACT: To evaluate the associations between genetic polymorphisms of glutathione S-transferase M1 and T1 (GSTM1 and GSTT1), smoking and susceptibility to colorectal cancer.
A case-control study of 126 patients and 343 healthy controls was conducted to investigate the role of GSTM1 and GSTT1 polymorphisms in colorectal cancer. Genotypes of GSTM1 and GSTT1 polymorphisms were analyzed by multiplex allele-specific polymerase chain reaction (PCR).
The frequencies of GSTM1 null and GSTT1 null genotypes were 55.5% and 20.4%, respectively. After adjustment for age and sex, among those with GSTT1 null genotype, the GSTM1 null genotype had a significant increased risk of rectal cancers compared to GSTM1 non-null genotype (OR=9.74, 95% CI, 1.13 - 83.85). A 2.22-fold risk of colon cancers was associated with GSTM1 null genotype compared to GSTM1 non-null genotype among current smokers (P >0.05). Individuals with GSTT1 null genotype and currently smoking had a significant risk of colon cancers (OR = 4.55, 95% CI, 1.14 - 18.17), and rectal cancers (OR = 4.60, 95% CI, 1.11 - 19.11).
This study suggests that certain null GSTM1 and GSTT1 genotypes may be associated with an elevated risk of colorectal cancer which may be modified by interaction of the two genetic polymorphisms and cigarette smoking.
Zhonghua zhong liu za zhi [Chinese journal of oncology] 11/2004; 26(11):645-8.
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ABSTRACT: To understand the incidence of colorectal cancer in population drinking or not and to validate the relationship between drinking and colorectal cancer.
The data obtained from a questionnaire used in a population-based prospective screenings study in ten countries of Jiashan County was examined. A total of 64,102 men and women aged 30 y and older without history of cancer at baseline and a subcohort of 29,044 of them drinking past and current was conducted. Cox regression model was applied to estimate relative risk (RR).
After 10 years follow-up,107 colon cancer and 135 rectal cancer cases were identified. Among drinkers and abstainers, the incidence density of colorectal cancer was 36.18 per 100 thousand and 37.26 per 100 thousand, respectively and there wasn't statistical significance(Z=0.52, P>0.05); The crude RR (95%CI) for drinker compared with never drinkers was 0.97(0.75 approximately 1.25), and the multivariable-adjusted RR (95%CI) was 1.13(0.87 approximately 1.48). The research power of this study was 96.99%.
Alcohol drinking isn't one of the risk factors of colorectal cancer among Jiashan County population.
Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences 10/2004; 33(5):411-5.
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ABSTRACT: To investigate the relationship between methylenetetrahydrofolate reductases (MTHFR) polymorphisms and colorectal cancer susceptibility.
A case-control study of 126 patients and 343 healthy controls was conducted to investigate the roles of MTHFR C677T and A1298C polymorphisms in colorectal cancer development. Genotypes of C677T and A1298C polymorphisms were analyzed by polymerase chain resction-restriction fragment length polymorphism (PCR-RFLP) methods.
The frequencies of MTHFR 677T and 1298C allele were 39.7% and 17.1%, respectively. After adjustment for age and sex, the MTHFR 1298C alleles seemed to have reduced association on the risk of colorectal cancer comparing to wild types. Among those with 677T and 1298A alleles, a decreased risk of colorectal cancer was observed: a 4-fold decrease in colorectal cancer risk (OR = 0.552, 95% CI: 0.265 - 1.150) in those with 677T and 1298C alleles. Men who were ex-drinkers and with MTHFR 1298C allele had a 2-fold increase in risk of colorectal cancer (OR = 3.307, 95% CI: 0.521 - 17.698) while no increased risk was seen among those current-drinkers.
This study suggested that certain MTHFR C677T and A1298C might be associated with the risk of colorectal cancer development. The interaction between MTHFR 1298AC polymorphisms and ex-drinking might also serve as a risk factor of colorectal cancer.
Zhonghua liu xing bing xue za zhi = Zhonghua liuxingbingxue zazhi 08/2004; 25(7):612-6.
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ABSTRACT: To investigate PstI allelic variants of cytochrome P450 2E1 (CYP2E1), the interaction effect on salted food and their role in risk for colorectal cancer.
The genotypes of CYP2E1 PstI restriction fragment length polymorphism were analyzed in 126 colorectal cancer cases and 343 normal controls. The unconditional logistic regression was applied to estimate the OR and its 95% CI.
The CYP2E1 C1/C1, C1/C2 and C2/C2 genotypes were found respectively in 61.8%, 35.8% and 2.4% of normal control, similar to rectal cancer cases. The percentage of PstI variant genotype (54.9%: 52.9% C1/C2 and 2.0% C2/C2) in colon cancer cases was significantly higher than that in controls (adjusted OR1.979, 95% CI 1.090 approximately 3.595). Stratified analysis suggested an interaction between CYP2E1 C2 allele and salted food. The odds ratio (OR) for the CYP2E1 variant genotype, salted food eaten weekly or biweekly and eaten every day or every other day were 1.935, 2.122 and 2.315, respectively, while those of salted food combined with variant genotype eaten weekly or biweekly and eaten every day or every other day were 2.272 and 3.127. The role in risk for rectal cancer was different from that for colon cancer. Whatever the CYP2E1 genotype is, the risk for rectal cancer came to marked when salted food was consumed weekly or biweekly (OR = 2.646 and 2.297, respectively). However, none but the combined effect of variant genotype and salted food eaten every day or every other day had the notably risk for colon cancer and the odds ratio suddenly increased to 4.262 (95% CI 1.395 approximately 13.017), 1.69-fold higher than that of wild genotype (P = 0.072).
The CYP2E1 C2 allele is a susceptibility factor for colorectal cancer, especially for colon cancer, and there is an apparent gene-environment interaction between the susceptible genotype and salted food.
Zhonghua yu fang yi xue za zhi [Chinese journal of preventive medicine] 06/2004; 38(3):162-6.
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ABSTRACT: The pollution of drinking water, for example river and pool, has long been recognized to be associated with an increased risk of colorectal cancer (CRC) in previous epidemiological studies. There is little prospect cohort study with person-years directly on the relative risks of different sources of drinking water for CRC.
From May 1989 to April 1990, a screening for CRC was carried out among residents aged 30 and over 30 years in 10 villages and towns of Jiashan in China. A total of 64115 residents who participated the screening were classified into 5 cohorts by the source of drinking water and were followed-up for CRC incidence through a tumor reporting system including a rapid reporting system of CRC Registry and for death instance through Death Registration of Jiashan. After 11 years of follow-up, person-years calculated with every cohort member, the incidence densities of CRC with different sources of drinking water were analyzed respectively. Poisson regression was used to control potential confounding variables including demography variables and smoke history and to attain crude and adjusted relative risks based on person-years.
A trend was seen toward increasing incidence rates of colorectal cancer from municipal, river, channel, mixed water to well source in turn as shown as 29.61, 32.67, 33.45, 40.87, 58.67 per 100,000 inhabitants, and only the role in risk of well water was marked different from municipal water (P< 0.05). After adjusted the confounding variables by multi-Poisson regression, we found the significant risk of drinking well water for colon cancer, rectal cancer, and colorectal cancer. The relative risks were 1.741 (95%CI 1.001-3.029), 2.228 (95%CI 1.432-3.466), and 2.022 (95%CI 1.432-2.854), respectively.
Drinking well water long is a risk factor for colorectal cancer in Jiashan, especially for rectal cancer.
Ai zheng = Aizheng = Chinese journal of cancer 06/2004; 23(5):550-4.
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ABSTRACT: To set up a mathematic model for determining individual risk and population risk of gastric carcinoma.
Based on principles and methods of probability and fuzzy mathematics, a case-control study was quantified and a mathematic model for the screening of gastric carcinoma was set up. Using two different calculation methods of weight coefficients, the thresholds were identified as 0.20 and 0.17, respectively. This mathematic model was then used to examine 63 cases and 693 normal persons.
The sensitivities and specificities were 69% and 63%. The different calculative methods of weight coefficients did not affect the results of the identification.
The sensitivities and specificities were satisfactory indicating that it was convenient, feasible, economic and could meet the contented screening rate. It could be used to determinate the risk for gastric carcinoma both on individual and on population.
Zhonghua liu xing bing xue za zhi = Zhonghua liuxingbingxue zazhi 05/2003; 24(4):310-3.
