Environmental and genetic interactions of esophageal and liver cancer in two high-risk areas, China
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Two case-control studies were carried out in this dissertation research to explore environmental and genetic interactions of esophageal and liver cancer in two high-risk populations. In the esophageal cancer case-control study, including 190 esophageal squamous cell carcinoma (ESCC) patients and 380 age-, gender- and residency- matched controls from Huaian, urinary free fumonisin B1 (FB1), sphinganine (Sa), sphingosine (So), Sa/So ratio, oxidative stress biomarker 8-hydroxy-2’-deoxyguanosine (8-OHdG), and genetic polymorphisms of genes, GSTT1, GSTM1, hOGG1, XPD, COX-2, NF-κB, TNF-α, and iNOS were evaluated. Analysis of questionnaires revealed that esophageal lesion, preference for salty food (ten-years-ago), preference for hot food (ten-years-ago), frequent pickled/salty food intake, mildewed food intake (ten-years-ago), and first-degree family history of cancer were associated with increased ESCC risk, while body mass index, frequent garlic intake, and tea drinking were protective factors. High levels of 8-OHdG, free FB1, and polymorphic XPD 751 Gln genotype were associated with increased risk for ESCC. Additive effects were observed for XPD 751 Gln genotype and high free FB1 (OR=9.35; 95% CI: 4.16–21.04), as well as XPD 751 Gln genotype and frequent pickled/salty food intake (OR=5.70, 95%CI: 2.42–13.43). The association between free FB1 level and ESCC risk suggests urinary free FB1 as a good FB1 exposure biomarker for future human epidemiological studies. In the hepatocellular carcinoma (HCC) case-control study, including 60 HCC patients and 120 age-, gender- and residency- matched controls from Southern Guangxi area, hepatitis B virus (HBV) genotype and basic core promoter (BCP) mutations, as well as serum level of aflatoxin B1 (AFB1)-lysine adduct were determined. The 1762T/1764A double mutations, 1753V mutations, and 1752V mutations were associated with HCC risk. Additive effects were observed for high serum AFB1 -lysine adduct levels and 1762T/1764A double mutations (OR=6.94, 95% CI: 1.68–27.78), as well as 1753V mutations (OR=5.13, 95% CI: 1.79–14.71). These data confirmed the association of BCP mutations and their interactions with dietary AFB1 exposure on HCC risk in this high-risk population. Overall, strong environmental (chemical and viral) and genetic interactions were found to play important roles in HCC and ESCC formation in these two high-risk populations.