Background: Ataxia-telangiectasia (A-T) is an autosomal recessive disease characterized by neurological and immunological symptoms, radiosensitivity, and cancer predisposition. Heterozygous carriers of risk mutations in the A-T gene are predisposed to epithelial cancers. We initiated a study to elucidate the frequency and clinical relevance of ATM gene mutations in lung cancer patients of the young (LUCY) and compared the results with population-based control subjects from southwest Germany (KORA=Cooperative Health Research in the Region of Augsburg).
Methods: In this study, the clinical relevance of ATM gene mutations (S707P; 1066-6T-->G; 2250G-->A, 7630A-->C, E1978X, R2443X, 3801delG, S49C, and D2625E&A2626P, L1420F, P1045R) in 183 young lung cancer patients (<50 years) is evaluated. The control population was comprised of 200 cancer-free subjects from the KORA study.
Results: A total of 25 heterozygous carriers of ATM in the LUCY, respectively; 32 heterozygotes in the KORA group were identified. The observed allele frequencies in the LUCY cases were within the range detected for the control subjects (KORA). Multiple analyses of lung cancer patients who carried at least one risk allele of the ATM did not show significantly elevated or reduced risks.
Conclusions: In this study, 16% of the German control subjects had ATM variants. ATM variants were detected in about 14% of the lung cancer patients and did not differ significantly from the control subjects. In comparison to young lung cancer patients, ATM gene mutations had no detectable relevant modifying effect on lung cancer risk.