The polymorphisms and haplotypes of WWOX gene are associated with the risk of lung cancer in southern and eastern Chinese populations.
The WW domain-containing oxidoreductase (WWOX) gene is an identified tumor suppressor gene, of which several single nucleotide polymorphisms have been reported to contribute to cancer susceptibility. We hypothesized that genetic variations in WWOX are associated with lung cancer risk. In two independent case-control studies conducted in southern and eastern Chinese, we genotyped five tagSNPs of WWOX gene (rs10220974C > T, rs3764340C > G, rs12918952G > A, rs383362G > T, and rs12828G > A) in 1,559 lung cancer cases and 1,679 controls. Logistic regression analysis showed that two tagSNPs (rs3764340C > G; rs383362G > T) were significantly associated with lung cancer risk in dominant model (rs3764340C > G, GC/GG vs. CC: adjust OR = 1.35, 95% CI = 1.11-1.65; rs383362G > T, TG + TT vs. GG: adjust OR = 1.33, 95% CI = 1.14-1.55). The haplotype analysis further shown that the haplotype "G-T" was associated with the highest increased risk of lung cancer (OR = 2.20; 95% CI = 1.43-3.37). After combined these two loci, the number of the risk genotypes was associated with increased cancer risk in a dose-response manner (Ptrend  = 3.16 × 10(-6) ). In addition, a gene-based association analysis by using VEGAS software suggested the WWOX as a susceptible gene for lung cancer (P = 0.009). However, for rs10220974C > T, rs12918952G > A, and rs12828G > A, no significant association was observed for lung cancer risk. Taken together, our data suggested that genetic variants in WWOX may be genetic biomarkers for susceptibility to lung cancer.
The Institute for Chemical Carcinogenesis, The State Key Lab of Respiratory Disease, Guangzhou Medical University, Guangzhou, P.R. China; Guangzhou Chest Hospital, Guangzhou, P.R. China.
Dongsheng
D
Huang
Fuman
F
Qiu
Lei
L
Yang
Yinyan
Y
Li
Mei
M
Cheng
Hui
H
Wang
Guanpei
G
Ma
Yunnan
Y
Wang
Min
M
Hu
Weidong
W
Ji
Yifeng
Y
Zhou
Jiachun
J
Lu
D000230:Adenocarcinoma / Q000453:epidemiology / Q000209:etiology; D044466:Asian People / Q000235:genetics*; D014408:Biomarkers, Tumor / Q000235:genetics; D018287:Carcinoma, Large Cell / Q000453:epidemiology / Q000209:etiology; D002294:Carcinoma, Squamous Cell / Q000453:epidemiology / Q000209:etiology; D016022:Case-Control Studies; D002681:China / Q000453:epidemiology; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D008175:Lung Neoplasms / Q000453:epidemiology / Q000209:etiology*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D010088:Oxidoreductases / Q000235:genetics*; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D012307:Risk Factors; D055752:Small Cell Lung Carcinoma / Q000453:epidemiology / Q000209:etiology*; D025521:Tumor Suppressor Proteins / Q000235:genetics*; D000074584:WW Domain-Containing Oxidoreductase
D014408:Biomarkers, Tumor; D025521:Tumor Suppressor Proteins; D010088:Oxidoreductases; D000074584:WW Domain-Containing Oxidoreductase; C486071:WWOX protein, human