Review and pooled analysis of studies on MTHFR C677T polymorphism and esophageal cancer

Abstract

Esophageal cancer has been associated with tobacco and alcohol consumption, gastric reflux, exposure to nitrosamines from food or other environmental sources, and diets lacking folate. Susceptibility to esophageal cancer may be modified by functional polymorphisms in genes along the folate metabolic pathway, such as methylenetetrahydrofolate reductase (MTHFR). The C677T polymorphism is the most common functional variant, leading to a reduction in enzyme activity. We report a pooled analysis of 5 studies on the association of MTHFR C677T polymorphism and esophageal cancer, including 725 cases and 1531 controls. A significant association between the MTHFR 677 TT genotype and esophageal cancer was observed (OR = 2.63, 95% CI: 1.75–3.94), although there was significant heterogeneity between studies. A sensitivity analysis excluded one study; the association between TT genotype and esophageal cancer was still present, although of reduced magnitude (OR = 1.57, 95% CI: 0.96–2.56). A significant interaction between smoking and TT genotype on esophageal cancer risk was observed, while no interaction was observed between alcohol consumption and genotype.

ACMG Practice Guideline: lack of evidence for MTHFR polymorphism testing

“…20 The potential associations between MTHFR genotype status and a number of medical complications have been evaluated using methodologies such as case-control, cohort, Mendelian randomization, and meta-analysis. A modest positive association has been found between the MTHFR "thermolabile" polymorphism and many different medical complications, including, but not limited to, thromboembolic disease (in non-North-American populations only), 21,22 stroke, [23][24][25][26][27] aneurysm, 28 peripheral artery disease, 29 migraine, 30 hypertension, 31,32 recurrent pregnancy loss, 33,34 male infertility, 35,36 risk for offspring with neural tube defects, 37,38 certain cancers, [39][40][41] neuropsychiatric disease, 42 and chemotherapy toxicity. 43,44 …”

The MTHFR C677T Polymorphism and Prostate Cancer Risk: New Findings from a Meta-analysis of 7306 Cases and 8062 Controls

“…Such change would disturb the homeostasis of folate metabolism, which was believed to be associated with the occurrence and development of several chronic diseases. Systematic reviews and meta-analysis revealed the MTHFR SNP C677T could increase the risk of developing schizophrenia, congenital heart defects, esophageal cancer, gastric cancer and breast cancer (Lewis et al, 2005;Langevin et al, 2009;Dong et al, 2010;Zhang et al, 2010;Yin et al, 2012) while probably playing as a preventive factor against colorectal cancer and children acute lymphoblastic leukemia (Hubner et al, 2007;Taioli et al, 2009;Yan et al, 2012). There were also many studies concerning the association between prostate cancer risk and SNP C677T, however, no conclusiveness was achieved: Heijmans (Heijmans et al, 2003) suggested MTHFR SNP C677T be a risk factor of prostate cancer in Dutch population, but HSI-CHIN WU found the polymorphism conferred a significant decreased risk of the disease; moreover, some studies showed no statistical relationship between them (Stevens et al, 2008).…”

Alcohol consumption and corresponding factors: A novel perspective on the risk factors of esophageal cancer

“…The homozygote and heterozygote of 667T exhibit a 30 and 65% activity, respectively, compared with the 100% activity exhibited by the 677CC genotype (73). Previous case-control studies and meta-analyses have revealed that the MTHFR C677T allele increased the risk of developing ESCC (74)(75)(76)(77)(78). In coordination with ADLH2*2, individuals with C677T demonstrated elevated ORs (74).…”