Different roles of MTHFR C677T and A1298C polymorphisms in colorectal adenoma and colorectal cancer: a meta-analysis.
Association studies on the MTHFR polymorphisms (C677T and A1298C) in colorectal cancer (CRC) and colorectal adenoma have shown conflicting results. We performed a meta-analysis to better assess the purported associations. Overall, the 677T allele (10,131 patients and 15,362 controls) showed a small but significant protective effect against CRC compared to the 677C allele [P=0.0003, odds ratio (OR)=0.93; 95% confidence interval (CI) 0.89-0.98, P=0.22 (for heterogeneity)] for a worldwide population. Meta-analyses of other genetic contrasts suggested that the 677T allele is more likely to affect CRC in a recessive genetic model worldwide (P<0.0001, OR=0.86; 95% CI 0.76-0.96, P=0.06) and in Asians (P=0.0005, OR=0.75; 95% CI 0.64-0.88, P=0.71). Similarly, we found a significantly decreased risk of CRC for 1298C polymorphism (4,764 CRC patients and 6,592 controls) for a recessive genetic model worldwide (P=0.005, OR=0.81; 95% CI 0.70-0.94, P=0.40) and in Caucasians (P=0.04, OR=0.75 95% CI 0.57-0.99, P=0.35). No evidence of association of C677T (4,616 patients and 6,338 controls) and A1298C (1,272 patients and 1,684 controls) with colorectal adenoma were found. The evidence accumulated suggests that MTHFR may represent a low-penetrance susceptible gene for CRC, and that the two polymorphisms might protect against colorectal adenoma developing into cancer. A larger single study is required to further evaluate gene-gene and gene-environment interactions for MTHFR polymorphisms and the cancer risk in a specific population.
Huang
Yan
Y
State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Science, Fudan University, Shanghai, 200433, People's Republic of China.
Han
Shizhong
S
State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Science, Fudan University, Shanghai, 200433, People's Republic of China.
Li
Yao
Y
State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Science, Fudan University, Shanghai, 200433, People's Republic of China.
Mao
Yumin
Y
State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Science, Fudan University, Shanghai, 200433, People's Republic of China.
Xie
Yi
Y
State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Science, Fudan University, Shanghai, 200433, People's Republic of China. yxie@fudan.edu.cn.
D000236:Adenoma / Q000235:genetics*; D000483:Alleles; D015179:Colorectal Neoplasms / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006801:Humans; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics* / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide
D042965:Methylenetetrahydrofolate Reductase (NADPH2)