Independent and combined effects of environmental factors and CYP2C19 polymorphisms on the risk of esophageal squamous cell carcinoma in Fujian Province of China.

BACKGROUND: The purpose of this study was to explore the effects of CYP2C19 gene polymorphisms and various environmental factors and their interactions on the risk of esophageal squamous cell carcinoma (ESCC) in a Chinese Han population. METHODS: A 1:2 frequency-matched case control study of 285 patients and 570 controls was conducted from June 2010 to May 2011 in AnXi of Fujian province, China. Environmental factors were investigated using a self-administered questionnaire and genotypes were determined using polymerase chain reaction restriction fragment length polymorphism based methods. Unconditional logistic regression models were used for statistical evaluation. RESULTS: Current or former smoking, consumption of pickled vegetables or hot beverages/food, having a first degree relative with ESCC and history of reflux esophagitis were significantly associated with increased ESCC risk, whereas tea drinking and consumption of fresh vegetables and fruits were significantly associated with decreased risk. The CYP2C19*2 GA/AA genotype was significantly more prevalent in ESCC patients and individuals with at least one copy of the CYP2C19*2 A allele had a 3.19-fold increased risk (adjusted 95% confidence interval (CI): 2.21-4.61, P < 0.001) of ESCC compared with those without this allele. We found no significant associations between CYP2C19*3 genotypes and ESCC. The Cyp2C19*2 polymorphism appeared to have a multiplicative joint effect with tea drinking and hot beverage/food consumption (gene-tea drinking: P(interaction) = 0.042; hot beverage/food consumption: P(interaction) = 6.98 × 10(-6)) and an additive joint effect with pickled vegetable consumption (interaction contrast ratio = 1.96, 95% CI: 0.12-3.80). CONCLUSIONS: Our findings suggest that the CYP2C19*2 polymorphism plays an important role in the development of ESCC in the Chinese population, modified by tea drinking and consumption of pickled vegetables or hot beverages/food. Further studies are warranted to confirm our results.

NQO1 609C>T polymorphism interaction with tobacco smoking and alcohol drinking increases colorectal cancer risk in a Chinese population.

BACKGROUND: NAD (P)H:quinone oxidoreductase (NQO1) catalyzes the activation of some environmental procarcinogens present in tobacco smoke or the diet. We conducted a hospital-based case-control study to evaluate the potential association between NQO1 609C>T polymorphisms and colorectal cancer risk in a Chinese population. METHODS: The study population comprised 672 histologically confirmed colorectal cancer patients and 672 frequency-matched control subjects without cancer or systemic illness. We used PCR restriction fragment length polymorphism-based methods for genotyping analyses and unconditional logistic regression model for statistical evaluations. RESULTS: The risk of colorectal cancer increased with the level of smoking and decreased with the consumption of tea, fresh fruits, and vegetables. In addition, we found that the NQO1 609 CT and TT genotypes were associated with an increased risk of colorectal cancer (CT: adjusted OR=2.02, 95% CI=1.55-2.57; TT: adjusted OR=2.51, 95% CI=1.82-3.47), compared with the CC genotype. Moreover, NQO1 609C>T appeared to have a multiplicative joint effect with both tobacco smoking and alcoholic drinking (P for multiplicative interactions were 0.0001 and 0.013, respectively) on colorectal cancer risk. CONCLUSION: Our findings suggest that the NQO1 609C>T polymorphism plays an important role in the development of colorectal cancer in the Chinese population, which is strengthened by alcohol drinking or tobacco smoking.

[Relationship between genetic polymorphism of ERCC1 and susceptibility to liver cancer].

OBJECTIVE: To investigate the association between genetic polymorphisms of ERCC1-C8092A and susceptibility to liver cancer, as well as the gene-environmental interaction on the etiology of liver cancer in Fuzhou. METHODS: A case-control study was conducted to collect the information on environmental exposure while genetic polymorphism of ERCC1 was analyzed by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. General relative risk regression models were further applied to fit the interaction between genetic polymorphisms of ERCC1-C8092A and the environmental factors of liver cancer. RESULTS: ERCC1-C8092A variant genotypes were associated with significant increasing risk of liver cancer adjusted odds ratio (OR = 3.789, 95%CI: 2.792 - 5.142), compared to the wild-type homozygote. Data from the analysis of interaction showed that genetic polymorphism of ERCC1-8092A appeared super-additive interaction with drinking pond-ditch or with hepatitis B, and super-multiplicative interaction with eating moldy food. CONCLUSION: The point mutation in ERCC1-8092A was possibly susceptible to liver cancer, and related synergistically with other risk factors in hepatocelluar carcinogenesis in Fuzhou.