RT Journal Article SR Electronic T1 Thymidylate Synthase Promoter Polymorphism, Interaction with Folate Intake, and Risk of Colorectal Adenomas JF Cancer Research JO Cancer Res FD American Association for Cancer Research SP 3361 OP 3364 VO 62 IS 12 A1 Ulrich, Cornelia M. A1 Bigler, Jeannette A1 Bostick, Roberd A1 Fosdick, Lisa A1 Potter, John D. YR 2002 UL http://cancerres.aacrjournals.org/content/62/12/3361.abstract AB Thymidylate synthase (TS) is a key enzyme in folate metabolism and the primary target of 5-fluorouracil. A repeat polymorphism in the TS promoter enhancer region (2rpt versus 3rpt of 28 bp) is associated with decreased expression, and a 6-bp deletion in the 3′untranslated region may affect RNA stability. We investigated the role of TS polymorphisms in a case control study of adenomatous polyps (510 cases and 604 polyp-free controls). Multivariate-adjusted odds ratios (ORs; 95% confidence interval) for TSER 2rpt/3rpt and 2rpt/2rpt compared with 3rpt/3rpt were 0.8 (0.6–1.2) and 0.9 (0.6–1.3), respectively. We observed a significant gene-nutrient interaction between the TSER polymorphism and folate intake: among 3rpt/3rpt individuals (greater expression), folate intake > 440 μg/day (highest tertile) versus ≤440 μg/day was associated with a 2-fold decreased risk [ORs 1.0 (reference group) versus 0.5 (0.3–0.9)]. However, among 2rpt/2rpt individuals, high folate intake was associated with a 1.5-fold increased risk [ORs 0.6 (0.4–0.9) versus 0.9 (0.5–1.5; P for interaction = 0.03)]. Vitamin B12 showed a similar trend (P = 0.08). No clear pattern was seen with the TS 1494del6 polymorphism. These findings raise questions regarding the molecular pathways linking folate metabolism and colorectal carcinogenesis, including whether high folate is beneficial in the presence of all metabolic genotypes. ©2002 American Association for Cancer Research.