Journal Article

<i>CYP1A1</i> and <i>CYP1B1</i> polymorphisms and risk of lung cancer among never smokers: a population-based study

A.S. Wenzlaff, M.L. Cote, C.H. Bock, S.J. Land, S.K. Santer, D.R. Schwartz and A.G. Schwartz

in Carcinogenesis

Volume 26, issue 12, pages 2207-2212
Published in print December 2005 | ISSN: 0143-3334
Published online July 2005 | e-ISSN: 1460-2180 | DOI:
CYP1A1 and CYP1B1 polymorphisms and risk of lung cancer among never smokers: a population-based study

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The cytochrome P450 (CYP) superfamily of enzymes catalyse one of the first steps in the metabolism of carcinogens such as polycyclic aromatic hydrocarbons, nitroaromatics and arylamines. Polymorphisms within the CYP1A1 gene have been shown to be associated with lung cancer risk, predominantly among Asian populations. Despite functional evidence of a possible role of CYP1B1 in lung cancer susceptibility, only a few studies have evaluated polymorphisms in this gene in relation to lung cancer susceptibility. This population-based study evaluates polymorphisms in both of these CYP genes within never smokers, most of whom had environmental tobacco smoke (ETS) exposure. Cases (n = 160) were identified through the metropolitan Detroit Surveillance, Epidemiology and End Results program, and age, sex and race-matched population-based controls (n = 181) were identified using random digit dialing. Neither CYP1A1 MspI nor CYP1A1 Ile462Val was associated with lung cancer susceptibility among Caucasians or African-Americans. Among Caucasians, however, CYP1B1 Leu432Val was significantly associated with lung cancer susceptibility odds ratio (OR) for at least one valine allele = 2.87 [95% confidence interval (CI) 1.63–5.07]. Combinations of this Phase I enzyme polymorphism along with selected Phase II enzyme polymorphisms (GSTM1 null, GSTP1 Ile105Val and NQO1 C609T) were evaluated. The combination of CYP1B1 Leu432Val and NQO1 C609T appeared to be associated with the highest risk of lung cancer (OR = 4.14, 95% CI 1.60–10.74), although no combinations differed significantly from the risk associated with CYP1B1 Leu432Val alone. When individuals were stratified by household ETS exposure (yes/no), CYP1B1 Leu432Val alone and in combination with Phase II enzyme polymorphisms was more strongly associated with increased lung cancer susceptibility among those with at least some household ETS exposure. Additional studies will be required to further validate these findings among never smokers and to evaluate the effects of this polymorphism among smoking populations as well.

Keywords: CYP, cytochrome P450; ETS, environmental tobacco smoke; GSTM1 null, glutatione S-transferase μ null; GSTP1 Ile105Val, glutathione S-transferase π Ile105Val; NQO1 C609T, NAD(P)H:quinone oxidoreductase 1 C609T; PAH, polycyclic aromatic hydrocarbons; RFLP, restriction fragment length polymorphism

Journal Article.  4795 words. 

Subjects: Clinical Cytogenetics and Molecular Genetics

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