Association of thymidylate synthase gene with endometrial cancer risk in a Chinese population.

Xu WH, Long JR, Zheng W, Ruan ZX, Cai Q, Cheng JR, Zhao GM, Xiang YB, Shu XO
Cancer Epidemiol Biomarkers Prev. 2009 18 (2): 579-84

PMID: 19190136 · PMCID: PMC2722075 · DOI:10.1158/1055-9965.EPI-08-0831

We comprehensively evaluated genetic variants in the thymidylate synthase (TYMS) gene in association with endometrial cancer risk in a population-based case-control study of 1,199 incident endometrial cancer cases and 1,212 age frequency-matched population controls. Exposure information was obtained via in-person interview, and DNA samples (blood or buccal cell) were collected. Genotyping of 11 haplotype-tagging single nucleotide polymorphisms (SNP) for the TYMS gene plus the 5-kb flanking regions was done for 1,028 cases and 1,003 controls by using the Affymetrix MegAllele Targeted Genotyping System. Of 11 haplotype-tagging SNPs identified, 7 that are located in flanking regions of the TYMS gene are also in the ENOSF1 (rTS) gene. The SNP rs3819102, located in the 3'-flanking region of the TYMS gene and in an intron of the ENOSF1 gene, was associated with risk of endometrial cancer. The odds ratio (95% confidence interval) for the CC genotype was 1.5 (1.0-2.2) compared with the TT genotype. Haplotype TTG in block 2 of the TYMS gene, which includes SNPs rs10502289, rs2298583, and rs2298581 (located in introns of the ENOSF1 gene), was associated with a marginally significant decrease in risk of endometrial cancer under the dominant model (odds ratio, 0.8; 95% confidence interval, 0.6-1.0). This study suggests that genetic polymorphisms in the TYMS or ENOSF1 genes may play a role in the development of endometrial cancer among Chinese women.

MeSH Terms (17)

Adult Aged Case-Control Studies Chi-Square Distribution China Endometrial Neoplasms Female Genetic Variation Genotype Haplotypes Humans Incidence Introns Middle Aged Polymorphism, Single Nucleotide Risk Thymidylate Synthase

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