Polymorphisms of cytosolic serine hydroxymethyltransferase and risk of lung cancer: a case-control analysis.

Journal Article (Journal Article)

Suboptimal DNA repair capacity is a risk factor for cancer that may be modulated by dietary nutrient intake, and serine hydroxymethyltransferase (SHMT) participates in folate metabolism and synthesis of purines and pyrimidines needed for DNA repair. Therefore, we tested our hypothesis that genetic variants of the cytosolic SHMT (SHMT1) gene are associated with lung cancer risk. In a hospital-based case-control study of 1032 non-Hispanic white lung cancer patients and 1145 matched cancer-free controls, we genotyped five common SHMT1 polymorphisms either in the promoter, exons, or 3'-untranslated regions. Although the genotype and allele frequency distribution of each SNP did not differ between cases and controls statistically significantly in the single-locus analysis, the rs638416 polymorphism in the promoter alone and the combined putative risk variant genotypes containing rs643333C, rs638416G, rs1979277T, rs3738G, and rs1979276C were associated with altered risk. Those carrying the combined 3+ risk variant genotypes had an increased risk of lung cancer (adjusted OR=1.65, 95% CI=1.05-2.57, compared with those having 0-1 risk genotypes; and OR=1.21, 95% CI=1.01-1.45, compared with those having 0-2 risk genotypes). The risk was more pronounced among older individuals (>61 years) or those having a low total folate intake or a high methionine intake. No evidence of interactions between the putative SHMT risk variant genotypes and the selected variables was found. These results suggest that SHMT1 variants may play a role in the etiology of lung cancer, and our findings need to be verified in larger prospective studies.

Full Text

Duke Authors

Cited Authors

  • Wang, L; Lu, J; An, J; Shi, Q; Spitz, MR; Wei, Q

Published Date

  • August 2007

Published In

Volume / Issue

  • 57 / 2

Start / End Page

  • 143 - 151

PubMed ID

  • 17420066

Pubmed Central ID

  • PMC2693017

International Standard Serial Number (ISSN)

  • 0169-5002

Digital Object Identifier (DOI)

  • 10.1016/j.lungcan.2007.03.002


  • eng

Conference Location

  • Ireland