Journal Article

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

Kengo Yoshida, Kei Nakachi, Kazue Imai, John B. Cologne, Yasuharu Niwa, Yoichiro Kusunoki and Tomonori Hayashi

in Carcinogenesis

Volume 30, issue 12, pages 2037-2041
Published in print December 2009 | ISSN: 0143-3334
Published online October 2009 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgp247
Lung cancer susceptibility among atomic bomb survivors in relation to CA repeat number polymorphism of epidermal growth factor receptor gene and radiation dose

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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 etiological environmental agents, including radiation exposure. The epidermal growth factor receptor (EGFR)-signaling pathway, regulating cellular radiation sensitivity, is an oncogenic cascade involved in lung cancer, especially adenocarcinoma. The cytosine adenine (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 (A-bomb) survivor cohort to evaluate a possible association of CA repeat polymorphism with lung cancer risk in radiation-exposed or negligibly exposed (<5 mGy) A-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, whereas 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.

Journal Article.  3680 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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