Polymorphism of cytosolic serine hydroxymethyltransferase, estrogen and breast cancer risk among Chinese women in Taiwan

Abstract

Cytosolic serine hydroxymethyltransferase (cSHMT) is key to intersection of folate-metabolic pathway, participating in the pyrimidine synthesis for DNA repair. Based on the hypothesis that variants of the cSHMT C1420T together with methionine synthase (MS A2756G) and 5,10-methylenetetrahydrofolate reductase (MTHFR C677T and A1298C) are associated with breast cancer, we performed a multigenic case-control study of the effects to breast cancer risk of four polymorphisms of folate-metabolizing genes against duration of estrogen exposure. Support of our hypothesis came from the following observations: (i) Allelic frequency of cSHMT C1420T was higher in the controls than in the cases, manifesting a 0.56-fold risk reduction in breast cancer (95%CI = 0.39-0.80); and this association was more significant in those women are susceptible to time of estrogen exposure. (ii) A joint effect of the cSHMT and MS polymorphisms significantly reduced susceptibility to breast cancer (aOR = 0.55; 95%CI = 0.34-0.88). (iii) There was a trend toward a reduced risk of breast cancer in women carrying a greater number of putative low-risk genotypes (Ptrend = 0.048). (iv) This synergistic effects on risk reduction was significantly interacted with length of estrogen exposure, exhibiting a longer time of estrogen exposure (> or =30 years), menarche-to-FFTP interval (>11 years), age at the first full-term pregnancy (< or =25 years), and body mass index (< or =24). In conclusion, our study provides support to account for the preferential role of cSHMT polymorphism to lower risk of female breast cancer, and such reduced risk would be more significant in carriers with the polymorphisms of MS and MTHFR genes.

Increased Risk for Second Primary Malignancies in Women with Breast Cancer Diagnosed at Young Age: A Population-Based Study in Taiwan

“…Despite a 4-fold increase in breast cancer incidence from 1979 to 2003 in Taiwan, 48.2% of female breast cancer cases diagnosed in 2005 remained under the age of 50 years, indicating that the preponderance of breast cancer in young females has not changed as lifestyle changes. To explain this early age of tumor onset, genetic polymorphisms (23,(33)(34)(35)(36) and the association between lipid profiles and breast cancer (37) have been rigorously studied; however, the etiologic factors remain obscure. Exploring the pathogenesis of second primary cancers might provide some insight into breast cancer etiologies in this region.…”

Single-nucleotide polymorphisms in one-carbon metabolism genes, Mediterranean diet and breast cancer risk: a case–control study in the Greek-Cypriot female population

“…However, in the wild-type MTR 2756AA genotype where the enzyme retains its normal activity, high intake of methionine and folate, through a diet rich in vegetables and fish (NutritionData 2014), might increase levels of methyl groups and of intracellular folate. These high levels would favour DNA methylation events as well as nucleotide synthesis, protecting thus against cancer (Cheng et al 2008;Lissowska et al 2007;Yu et al 2007). The protective effect of the high adherence to the PCA-derived dietary pattern in the MTR 2756AA carriers against BC risk may be explained by these anti-carcinogenic events.…”

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;…”