Combinations of cytochrome P-450 genotypes and risk of early-onset lung cancer in Caucasians and African Americans: A population-based study

Summary Polymorphisms in CYP1A1 and CYP1B1 genes in humans are associated with reduction of enzymatic activity towards several substrates, including those found in tobacco smoke. To investigate the potential role these polymorphisms have as modulators of early-onset lung cancer risk, a population-ba...

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Bibliographic Details
Published in:Lung cancer (Amsterdam, Netherlands) Netherlands), 2007-03, Vol.55 (3), p.255-262
Main Authors: Cote, M.L, Wenzlaff, A.S, Bock, C.H, Land, S.J, Santer, S.K, Schwartz, D.R, Schwartz, A.G
Format: Article
Language:English
Subjects:
Adenocarcinoma - ethnology
Adenocarcinoma - genetics
Adult
African Americans
African Americans - genetics
Amino Acids, Branched-Chain - genetics
Aryl Hydrocarbon Hydroxylases - genetics
Biological and medical sciences
Case-Control Studies
Caucasians
Cytochrome P-450 CYP1A1 - genetics
Cytochrome P-450 CYP1B1
Cytochrome p-450 polymorphisms
European Continental Ancestry Group - genetics
Exons
Female
Genotype
Hematology, Oncology and Palliative Medicine
Humans
Lung cancer
Lung Neoplasms - ethnology
Lung Neoplasms - genetics
Male
Medical sciences
Pneumology
Polymorphism, Genetic
Pulmonary/Respiratory
Smoking
Smoking - ethnology
Tobacco, tobacco smoking
Toxicology
Tumors
Tumors of the respiratory system and mediastinum
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Summary:Summary Polymorphisms in CYP1A1 and CYP1B1 genes in humans are associated with reduction of enzymatic activity towards several substrates, including those found in tobacco smoke. To investigate the potential role these polymorphisms have as modulators of early-onset lung cancer risk, a population-based case-control study involving early-onset lung cancer cases was performed. Biological samples were available for 383 individuals diagnosed prior to 50 years of age identified from the metropolitan Detroit Surveillance, Epidemiology and End Results (SEER) program and 449 age, race and sex-matched controls ascertained through random digit dialing. Genotype frequencies varied significantly by race for CYP1A1 Ile 462 Val and CYP1B1 Leu 432 Val genotypes, so all analyses were stratified by race. No association was seen between lung cancer risk and polymorphisms in CYP1A1 Msp1 or CYP1B1 Leu 432 Val for Caucasians or African Americans, after adjusting for age at diagnosis, sex, pack years of smoking and family history of lung cancer. In Caucasians, those with the IIe/Val genotype at CYP1A1 Ile 462 Val locus were at decreased risk of having lung cancer compared to those with the lle/lle genotype, after adjusting for age at diagnosis, sex, pack years of smoking and family history of cancer (OR = 0.41 95% Cl 0.19–0.90). These results were not replicated among the African American population, nor were they modified by amount of smoking.
ISSN:0169-5002
1872-8332
DOI:10.1016/j.lungcan.2006.11.002