ATM polymorphisms and risk of lung cancer among never smokers.
The ataxia-telangiectasia mutated (ATM) gene, an important caretaker of overall genome stability, is thought to play a role in the development of human malignancy. Therefore, we hypothesized that sequence variants in ATM may influence the disposition to lung cancer. In this hospital-based matched case-control study, nine ATM single nucleotide polymorphisms (rs189037, rs228597, rs228592, rs664677, rs609261, rs599558, rs609429, rs227062, and rs664982) were genotyped in 730 lung cancer patients and 730 healthy controls. Pairwise linkage disequilibrium among nine polymorphisms in the ATM gene was very high. None of the main effects of any of the ATM polymorphisms were related to the risk of lung cancer. Interestingly, ATM polymorphisms were significantly associated with lung cancer among never smokers, and the association was modulated by low-level exposure to carcinogens such as environmental tobacco smoke. When the haplotypes of nine ATM polymorphism sites were studied, no overall association between ATM haplotypes and risk of lung cancer was found. However, the frequency distribution of haplotypes between lung cancer cases and controls was significant in the never smokers (P=0.009), demonstrating that haplotypes have a significant effect on the risk of lung cancer. In conclusion, we found that never smokers with sequence variants of the ATM gene may be at increased risk for lung cancer. Our data also suggest this association may be further modified by exposure to environmental tobacco smoke. This study suggests support to the literature that ATM polymorphisms and environmental tobacco smoke exposure have a role in lung carcinogenesis among never smokers.
Lo
Yen-Li
YL
Institute of Population Health Sciences, National Health Research Institutes, 35 Keyan Road, Zhunan, Miaoli County 350, Taiwan.
Hsiao
Chin-Fu
CF
Jou
Yuh-Shan
YS
Chang
Gee-Chen
GC
Tsai
Ying-Huang
YH
Su
Wu-Chou
WC
Chen
Yuh-Min
YM
Huang
Ming-Shyan
MS
Chen
Hui-Ling
HL
Yang
Pan-Chyr
PC
Chen
Chien-Jen
CJ
Hsiung
Chao A
CA
D064007:Ataxia Telangiectasia Mutated Proteins; D016022:Case-Control Studies; D018797:Cell Cycle Proteins / Q000235:genetics*; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000235:genetics*; D004781:Environmental Exposure / Q000009:adverse effects; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D008175:Lung Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D011110:Polymorphism, Genetic; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects; D025521:Tumor Suppressor Proteins / Q000235:genetics*
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D025521:Tumor Suppressor Proteins; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases