Polymorphisms of cytosolic serine hydroxymethyltransferase and risk of lung cancer: A case–control analysis

Abstract

SummaryThe suboptimal DNA repair capacity is a risk factor for cancer that may be modulated by dietary nutrient intake, and the serine hydroxymethyltransferase (SHMT) participates in folate metabolism and synthesis of purine and pyrimidine 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.

Association of Folate-Pathway Gene Polymorphisms with the Risk of Prostate Cancer: a Population-Based Nested Case-Control Study, Systematic Review, and Meta-analysis

“…The SHMT1 1420T allele was associated with elevated plasma and RBC levels of folate in one (59) but not another study (60). In studies of associations with cancer risk, the SHMT1 1420T allele was reported to be associated with reduced risk of acute lymphocytic leukemia (58) and malignant lymphoma (61), but null findings have been reported for colorectal (60), bladder (62), breast (48), lung (63), and ovarian cancers (64). In the absence of a phenotypic effect of SHMT1 C1420T, and given the generally null findings of dietary and blood level studies with regard to vitamin B6 (8, 9, 11, 13), our result could be attributable to chance.…”

Sarcosine and other metabolites along the choline oxidation pathway in relation to prostate cancer—A large nested case–control study within the JANUS cohort in Norway

“…31 In addition, mathematical modeling of the one-carbon metabolism revealed that SHMT velocity remained relatively unchanged when decreasing the folate pool. 32 Nevertheless, the rare variant of the SHMT1 (rs1979277) polymorphism may be associated with higher folate status 33 and increased prostate cancer risk, 34 and SHMT polymorphisms were associated with increased risk of lung cancer 35 and ovarian cancer. 36 In addition to a likely role of SHMT activity, a probably much stronger determinant of plasma and tissue glycine concentration and flux is the activity of the mitochondrial glycine cleavage system.…”

C1420T Polymorphism of Cytosolic Serine Hydroxymethyltransferase and Risk of Cancer: a Meta-analysis

“…We excluded 17 studies and one population of a study (five subjects were overlapped in other publications (Koushik et al, 2006;Wang et al, 2006;Vainer et al, 2010;Mohammad et al, 2011;Naushad et al, 2011a); genotype frequencies of eight studies were not provided (Lee et al, 2007;Gibson et al, 2011;Metayer et al, 2011;Naushad et al, 2011b;Piskac-Collier et al, 2011;Galbiatti et al, 2012;Lautner-Csorba et al, 2013;Swartz et al, 2013); and four studies (Wang et al, 2007b;Yu et al, 2007;Patino-Garcia et al, 2009;Curtin et al, 2011;Naushad et al, 2012) and one of populations in a study (Steck et al, 2008) did not conform to HWE). A total of 28 case-control studies with 29 populations met our inclusion criteria (Skibola et al, 2002;Hishida et al, 2003;Chen et al, 2004;Skibola et al, 2004;Lightfoot et al, 2005;Zhang et al, 2005;Niclot et al, 2006;Hazra et al, 2007;Lim et al, 2007;Lissowska et al, 2007;Moore et al, 2007;van den Donk et al, 2007;Wang et al, 2007a;Cheng et al, 2008;Guerreiro et al, 2008;Steck et al, 2008;Berglund et al, 2009;de Jonge et al, 2009;…”