Genetic polymorphisms in folate and alcohol metabolism and breast cancer risk: a case–control study in Thai women

Abstract

Dietary folate as well as polymorphic variants in one-carbon metabolism genes may modulate risk of breast cancer through aberrant DNA methylation and altered nucleotide synthesis and repair. Alcohol is well recognized as a risk factor for breast cancer, and interactions with one-carbon metabolism has also been suggested. The purpose of this study is to test the hypothesis that genetic polymorphisms in the folate and alcohol metabolic pathway are associated with breast cancer risk. Twenty-seven single nucleotide polymorphisms (SNPs) in the MTR, MTRR, MTHFR, TYMS, ADH1C, ALDH2, GSTP1, NAT1, NAT2, CYP2E1 DRD2, DRD3, and SLC6A4 were genotyped. Five hundred and seventy patients with histopathogically confirmed breast cancer and 497 controls were included in the present study. Association of genotypes with breast cancer risk was evaluated using multivariate logistic regression to estimate odds ratios (OR) and their 95% confidence intervals (95% CI). Increased risk was observed for homozygotes at the MTR SNPs (rs1770449 and rs1050993) with the OR = 2.21 (95% CI 1.18-4.16) and OR = 2.24 (95% CI 1.19-4.22), respectively. A stratified analysis by menopausal status indicated the association between the NAT2 SNP (rs1799930) and breast cancer was mainly evident in premenopausal women (OR 2.70, 95% CI 1.20-6.07), while the MTRR SNP (rs162049) was significant in postmenopausal women (OR 1.61, 95% CI 1.07-2.44). Furthermore, SNPs of the genes that contribute to alcohol behavior, DRD3 (rs167770), DRD2 (rs10891556), and SLC6A4 (rs140701), were also associated with an increased risk of breast cancer. No gene-gene or gene-environment interactions were observed in this study. Our results suggest that genetic polymorphisms in folate and alcohol metabolic pathway influence the risk of breast cancer in Thai population.

Association of dietary intake of folate and MTHFR genotype with breast cancer risk

“…Reports regarding the association of folate metabolism and changes in MTHFR activity with breast cancer are conflicting (Alshatwi, 2010;Sangrajrang et al, 2010;Lajin et al, Z.G. Wang et al 2012).…”

“…Many studies have examined the association between MTHFR gene polymorphisms and risk of breast cancer, and suggested that MTHFR C677T and A1298C polymorphisms are associated with an increased or decreased risk of breast cancer (Le Marchand et al, 2004;Rossi et al, 2006;Yu and Chen, 2012;Jiao and Li, 2013). Previous studies reported the association between the MTHFR genotype polymorphisms and folate intake and risk of breast cancer (Alshatwi, 2010;Sangrajrang et al, 2010;Lajin et al, 2012), but the results are inconsistent. In our study, we conducted a hospitalbased case-control study to investigate the associations of dietary intake of folate and MTHFR C677T and A1298C polymorphisms with breast cancer in a Chinese population.…”

Germ-line MTHFR C677T, FV H1299R and PAI-1 5G/4G Variations in Breast Carcinoma

“…In contrast, limited findings are reported about failure of germ-line functional gene effect on familiar BC. Recent literature findings report the MTHFR C677T and A1298C polymorphisms and breast cancer risk in women in differen populations (Ericson et al, 2009;Gao et al, 2009;Eroglu and Akar, 2010;Qi et al, 2010;Sangrajrang et al, 2010;Eroglu and Akar, 2011;Hosseini et al, 2011;Akram et al, 2012;Diakite et al, 2012;Wu et al, 2012). The solid tumoural tissue samples from each patients were used for profilling the transcriptome analysis for the clinical follow-up and treatment and peripheral blood-EDTA samples were also used for germ-line thrombophilic gene analysis in the current cohort.…”

REV1 Genetic Polymorphisms and Breast Cancer Risk in Thai Women

“…Study population: Ascertainment of the cases and controls and their demographic characteristics were described previously (14,15). Brie‰y, cases were all new incident breast cancer patients histologically diagnosed at the National Cancer Institute in Bangkok and at the hospital in Khon Kaen province of North Eastern of ).…”

“…We also reported the genetic polymorphisms in estrogen, alcohol and folate metabolism enzyme (14,15). In this study, we present data on the association between REV1 polymorphisms and breast cancer risk in a case-control study of Thai women.…”