Association of polymorphisms in one-carbon metabolizing genes and lung cancer risk: a case-control study in Chinese population.
One-carbon metabolism facilitates the cross-talk between genetic and epigenetic processes, making it a good candidate for studying the risk of lung cancer. To investigate the role of common variants of one-carbon metabolizing genes on lung cancer risk, total 25 single nucleotide polymorphisms (SNPs) in 7 genes were genotyped among 500 incident lung cancer patients and 517 cancer-free controls. An increased risk was suggested for the variant allele carriers of MTHFR rs17037396 [odds ratio (OR)=1.39, 95% confidence interval (CI): 1.00-1.94] and rs3753584 (OR=1.46, 95% CI: 1.03-2.08), compared with subjects with wild homozygote, respectively, and the risk was more pronounced among older individuals (>60 years). In contrast, a decreased risk was observed for TYMS rs2853742 variant allele carriers (OR=0.44, 95% CI: 0.19-0.99) and MTHFD rs2236225 variant allele carriers (OR=0.76, 95% CI: 0.59-0.99). Haplotype analysis revealed that MTHFR "ACCACC" haplotype may contribute to the risk of lung cancer (OR=1.49, 95% CI: 1.03-2.14, local test p value 0.032). A data mining method, multifactor dimensionality reduction (MDR), predicted a four-factor interaction model (rs1801133, rs4659731, rs2273029 and rs699517) with the lowest average prediction error (45.08%, p<0.001). These findings suggest that genetic variants in one-carbon metabolizing genes might modulate the risk of lung cancer. Validation of these findings in larger studies is needed.
Liu
Hongliang
H
State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai 200433, China.
Jin
Guangfu
G
Wang
Haifeng
H
Wu
Wenting
W
Liu
Yanhong
Y
Qian
Ji
J
Fan
Weiwei
W
Ma
Hongxia
H
Miao
Ruifen
R
Hu
Zhibin
Z
Sun
Weiwei
W
Wang
Yi
Y
Jin
Li
L
Wei
Qingyi
Q
Shen
Hongbing
H
Huang
Wei
W
Lu
Daru
D
D044466:Asian People; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D019875:One-Carbon Group Transferases / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors
D019875:One-Carbon Group Transferases