Meta-analysis on MTHFR polymorphism and lung cancer susceptibility in East Asian populations

Abstract

Lung cancer is the most frequently occurring type of cancer worldwide and the leading cause of cancer mortality. Environmental and genetic factors play important roles in lung carcinogenesis. The aim of this meta-analysis was to investigate the association between methylenetetrahydrofolate reductase (MTHFR) polymorphism and the risk of lung cancer in East Asian populations. Related articles were identified through searching literature databases, such as PubMed, EMBASE, Web of Science, Chinese Biomedicine and CNKI. The odds ratio (OR) values in those studies were incorporated by meta-analysis to assess lung cancer susceptibility associated with the MTHFR mutation genotype. The MTHFR C677TT genotype exhibited a significantly increased risk of lung cancer compared to the MTHFR 677CC/CT genotype (OR=1.24; 95% CI, 1.01-1.52). No relationship was identified between the other MTHFR C677T genetic models and the risk of lung cancer and there was no significantly increased risk of lung cancer in A1298C genetic models. In a subgroup of hospital-based controls, according to the source of controls, the C677TT genotype exhibited a significantly increased risk of lung cancer, compared to the C677CC genotype (OR=3.01; 95% CI, 1.07-8.46). In the stratified analysis, the study indicated that the MTHFR 677TT genotype was associated with a significant increase in the risk of lung squamous carcinoma (OR=1.53; 95% CI, 1.09-2.14), whereas no association was observed between the MTHFR C677TT genotype and the risk of lung adenocarcinoma. No association was observed between MTHFR C677TT polymorphism and the risk of lung cancer when smoking was considered. In conclusion, the meta-analysis results suggested that MTHFR C677T polymorphisms exhibit a significantly increased risk of lung cancer and that the MTHFR 677TT genotype is associated with a significantly increased risk of lung squamous carcinoma.

MTHFR C677T and A1298C polymorphisms and lung cancer risk in a female Chinese population

“…Compared with the C677T gene polymorphism, the number of studies pertaining to the MTHFR A1298C gene polymorphism is relatively small. After a massive relative literature and meta-analysis was conducted, no statistically significant association was found between the MTHFR A1298C gene polymorphism and susceptibility to lung cancer, 9 but in this study, we reached the conclusion that the A1298C gene polymorphism is a protective factor in lung cancer. For example, the CC genotype carriers were at lower risk to develop lung cancer than carriers of the AA genotype.…”

“…A previous study determined that MTHFR C677T can modify the enzyme activity of MTHFR. 9 It has been reported that MTHFR C677T is associated with susceptibility to many malignancies, but the conclusion is not definitive. 10 – 15 Hajiesmaeil et al reported that MTHFR 677TT genotype played a protective role and that MTHFR 1298CC genotype could be seen as a genetic risk factor for cervical cancer.…”

State of Art of Cancer Pharmacogenomics in Latin American Populations

“…Mutations in the BRCA1/2 and MTHFR genes in Latin Americans were associated with breast and ovarian cancer [89,90,91,92,93,94,95,96,97,98,99,100,101,102,103], also observed in Asians and Caucasians [104,105,106,107]. Mutations in the CYP1A1 , GSTM1 , MTHFR , SRD5A2 , AR , and GSTA1 genes were relevant in prostate cancer in Latin Americans [108,109,110,111,112], also determined in Caucasians and Asians [113,114,115,116,117,118,119,120,121].…”

Individual and combined effect ofTP53, MDM2, MDM4, MTHFR, CCR5,andCASP8gene polymorphisms in lung cancer

“…The MTHFR gene is located on the short arm of chromosome 1 (1p36.3) and its cDNA has a total length of 2.2 kb [ 27 ]. MTHFR is involved in DNA methylation and synthesis as an important enzyme in the folic acid metabolic process [ 28 ]. The most common mutation is a C to T transition at nucleotide 677 (rs1801133, C677T) in exon 4, resulting in a substitution of alanine with valine [ 29 ].…”

“…The most common mutation is a C to T transition at nucleotide 677 (rs1801133, C677T) in exon 4, resulting in a substitution of alanine with valine [ 29 ]. The MTHFR T/T genotype exhibited a significantly increased risk of LC compared to the MTHFR C/C and C/T genotype [ 28 ].…”