title: Polymorphisms of methylenetetrahydrofolate reductase are associated with a high risk of nasopharyngeal carcinoma in a smoking population from Southern China.
abstract: Methylenetetrahydrofolate reductase (MTHFR) plays a central role in converting folate to a compound which serves as a methyl donor for DNA methylation, an epigenetic modification known to be dysregulated in carcinogenesis. This case-control study assessed the contribution of MTHFR polymorphisms to the risk of nasopharyngeal carcinoma (NPC). MTHFR genotypes C677T and A1298C in 529 NPC patients and 577 frequency-matched controls were determined by PCR-based restriction fragment length polymorphism. We found a 1.57-fold increased risk of NPC in subjects with the MTHFR 1298AC genotype compared to subjects with the MTHFR 1298AA genotype. In addition, an elevated NPC risk was also found in subjects with both the MTHFR 677CT and 1298AC genotypes [odds ratio (OR) = 2.15, 95% confidence interval (CI) = 1.37-3.39] compared to subjects with the 677CC/1298AA genotypes. Furthermore, we observed an additive interaction between MTHFR polymorphisms and smoking status on the increased risk of NPC. The OR was 6.72 (95% CI = 1.85-24.48) among heavy smokers (pack-years ≥15) carrying 677TT compared with nonsmokers carrying the 677CC genotype. The OR was 7.23 (95% CI = 4.22-12.38) or 12.75 (95% CI = 2.74-59.3) among subjects carrying the 1298AC or 1298CC genotype in heavy smokers (pack-years ≥15) compared with 1298AA in nonsmokers. Our results provide the first molecular epidemiological evidence that MTHFR polymorphisms associate with the risk of NPC and this association is especially noteworthy in heavy smokers.
authors: Department of Pathology, Sun Yat-sen University Cancer Center, Guangzhou, PR China.
authors: Yun
authors: Y
authors: Cao
authors: Xiao-Ping
authors: XP
authors: Miao
authors: Ma-Yan
authors: MY
authors: Huang
authors: Ling
authors: L
authors: Deng
authors: Xiao-Man
authors: XM
authors: Liang
authors: Dong-Xin
authors: DX
authors: Lin
authors: Yi-Xin
authors: YX
authors: Zeng
authors: Jian-Yong
authors: JY
authors: Shao
mesh_terms: D044466:Asian People / Q000235:genetics*; D016022:Case-Control Studies; D002681:China / Q000453:epidemiology; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008875:Middle Aged; D009303:Nasopharyngeal Neoplasms / Q000208:ethnology / Q000235:genetics*; D016017:Odds Ratio; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D012307:Risk Factors; D012907:Smoking / Q000235:genetics*
chemical_list: D042965:Methylenetetrahydrofolate Reductase (NADPH2)