Background: Esophageal cancer (EC) is the sixth most common cancer in the world and exhibits a dramatic geographic distribution in incidence and histological subtype. In China, EC is the fourth leading cause of cancer death, the predominant histologic type being squamous cell carcinoma (ESCC), as opposed to adenocarcinoma which is more common in developed counties of the western world. Recently it has been suggested that sex hormones may be associated with the risk of aero-digestive tract cancers including those of the colon, head and neck, and stomach. To evaluate the potential role of sex hormones in ESCC, we examined sex hormone metabolizing gene variants and ESCC risk in a high risk population from north central China.

Methods: A combined total of 1027 ESCC cases and 1452 controls from separate studies were genotyped for 752 tagged SNPs in 46 sex hormone-related genes. SNP-, gene-, and pathway-based associations with ESCC risk were evaluated using the adaptive rank-truncated product (ARTP) method and the additive model within unconditional logistic regression adjusted for age and sex. Statistical significance was determined through use of a permutation-based sampling procedure (20,000 permutations).

Results: No significant pathway-based association was observed when all 46 sex hormone genes were considered together (P=0.16). Gene-based associations with ESCC were observed for 6 genes: SULT2B1 (ARTP P=0.012), CYP1B1 (P=0.019), CYP3A7 (P=0.03), CYP3A5 (P=0.033), SHBG (P=0.037), and CYP11A1 (P=0.038). Of examined individual SNPs, sixty three SNPs in 21 genes were also statistically significant (P<0.05). Among the strongest effects observed were rs4149455 in SULT2B1 (per allele OR 0.81, 95% CI 0.72-0.91, P=0.0007); rs9341266 in CYP1B1 (OR 1.45, 1.16-1.82, P=0.001); rs17161780 in CYP3A5 (OR 1.19, 1.04-1.35, P=0.009); rs2005548 in CYP3A7 (OR 1.15, 1.02-1.29, P=0.02), and rs727428 in SHBG (OR 0.85, 0.76-0.96, P=0.01).

Conclusion: Genetic variation in specific sex hormone-related genes may contribute to ESCC risk among Chinese individuals at high risk for ESCC.

Citation Information: Cancer Prev Res 2010;3(12 Suppl):B27.

Copyright © 2010, American Association for Cancer Research
2010