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Elevated lung cancer risk is associated with deficiencies in cell cycle checkpoints: genotype and phenotype analyses from a case‐control study
Author(s) -
Zheng YunLing,
Kosti Ourania,
Loffredo Christopher A.,
Bowman Elise,
Mechanic Leah,
Perlmutter Donna,
Jones Raymond,
Shields Peter G.,
Harris Curtis C.
Publication year - 2010
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.24771
Subject(s) - lung cancer , genotype , quartile , oncology , biology , odds ratio , medicine , cancer , phenotype , cell cycle , cell cycle checkpoint , cancer research , immunology , genetics , gene , confidence interval
Cell cycle checkpoints play critical roles in the maintenance of genomic integrity and inactivation of checkpoint genes are frequently perturbed in most cancers. In a case‐control study of 299 non‐small cell lung cancer cases and 550 controls in Baltimore, we investigated the association between γ‐radiation‐induced G 2 /M arrest in cultured blood lymphocytes and lung cancer risk, and examined genotype‐phenotype correlations between genetic polymorphisms of 20 genes involving in DNA repair and cell cycle control and γ‐radiation‐induced G 2 /M arrest. The study was specifically designed to examine race and gender differences in risk factors. Our data indicated that a less efficient DNA damage‐induced G 2 /M checkpoint was associated with an increased risk of lung cancer in African American women with an adjusted odds ratio (OR) of 2.63 (95% CI = 1.01–7.26); there were no statistically significant associations for Caucasians, or African American men. When the African American women were categorized into quartiles, a significant reverse trend of decreased G 2 /M checkpoint function and increased lung cancer risk was present, with lowest‐ vs. ‐highest quartile OR of 13.72 (95% CI = 2.30–81.92, p trend < 0.01). Genotype‐phenotype correlation analysis indicated that polymorphisms in ATM, CDC25C, CDKN1A, BRCA2, ERCC6, TP53, and TP53BP1 genes were significantly associated with the γ‐radiation‐induced G 2 /M arrest phenotype. This study provides evidence that a less efficient G 2 /M checkpoint is significantly associated with lung cancer risk in African American women. The data also suggested that the function of G 2 /M checkpoint is modulated by genetic polymorphisms in genes involved in DNA repair and cell cycle control.

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