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Carcinogenesis Advance Access published online on October 20, 2009
Carcinogenesis, doi:10.1093/carcin/bgp247
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© The Author 2009. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Lung cancer susceptibility among atomic-bomb survivors in relation to CA repeat number polymorphism of epidermal growth factor receptor gene and radiation dose

Kengo Yoshida1, Kei Nakachi1, Kazue Imai1, John B. Cologne2, Yasuharu Niwa1, Yoichiro Kusunoki1 and Tomonori Hayashi1

1 Department of Radiobiology/Molecular Epidemiology
2 Department of Statistics, Radiation Effects Research Foundation (RERF), Hiroshima, Japan

Correspondence to: Kengo Yoshida, 5-2 Hijiyama Park, Minami Ward, Hiroshima City, 732-0815 Japan. Tel: +81-82-261-3131. Fax: +81-82-261-3170. E-mail: kyoshi{at}rerf.or.jp

Lung cancer is a leading cause of cancer death worldwide. Prevention could be improved by identifying susceptible individuals as well as improving understanding of interactions between genes and etiologic environmental agents, including radiation exposure. The EGFR signaling pathway, regulating cellular radiation sensitivity, is an oncogenic cascade involved in lung cancer, especially adenocarcinoma. The CA repeat number polymorphism in the first intron of EGFR has been shown to be inversely correlated with EGFR production. It is hypothesized that CA repeat number may modulate individual susceptibility to lung cancer. Thus, we carried out a case-cohort study within the Japanese atomic-bomb survivor cohort to evaluate a possible association of CA repeat polymorphism with lung cancer risk in radiation-exposed or negligibly exposed (< 5 mGy) atomic-bomb survivors. First, by dividing study subjects into Short and Long genotypes–defined as the summed CA repeat number of two alleles ≤ 37 and ≥ 38, respectively–we found that the Short genotype was significantly associated with an increased risk of lung cancer, specifically adenocarcinoma, among negligibly-exposed subjects. Next we found that prior radiation exposure significantly enhanced lung cancer risk of survivors with the Long genotype, while the risk for the Short genotype did not show any significant increase with radiation dose, resulting in indistinguishable risks between these genotypes at a high radiation dose. Our findings imply that the EGFR pathway plays a crucial role in assessing individual susceptibility to lung adenocarcinoma in relation to radiation exposure.

Key Words: cancer susceptibility • epidermal growth factor receptor • gene polymorphism • lung cancer • radiation

Received September 3, 2009; revised September 3, 2009; accepted October 8, 2009.


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