Carcinogenesis Advance Access originally published online on January 27, 2009
Carcinogenesis 2009 30(4):626-635; doi:10.1093/carcin/bgp033
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Tobacco and estrogen metabolic polymorphisms and risk of non-small cell lung cancer in women
1 Population Studies and Prevention Program, Karmanos Cancer Institute, 110 East Warren Avenue, Detroit, MI 48201, USA
2 Department of Internal Medicine
3 Cancer Biology Program
4 Applied Genomics Technology Center, Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI 48201, USA
5 Molecular Biology and Genetics Program, Karmanos Cancer Institute, 110 East Warren Avenue, Detroit, MI 48201, USA
* To whom correspondence should be addressed. Tel: +1 313 578 4204; Fax: +1 313 578 4306; Email: cotem{at}karmanos.org
To explore the potential role for estrogen in lung cancer susceptibility, candidate single-nucleotide polymorphism (SNPs) in tobacco and estrogen metabolism genes were evaluated. Population-based cases (n = 504) included women aged 18–74, diagnosed with NSCLC in metropolitan Detroit between November 2001 and October 2005. Population-based controls (n = 527) were identified through random digit dialing and matched on race and age. Eleven SNPs in 10 different genes were examined in relation to risk: CYP1A1 Msp1, CYP1A1 Ile462Val, CYP1B1 Leu432Val, CYP17, CYP19A1, XRCC1 Gln399Arg, COMT Val158Met, NQO1 Pro187Ser, GSTM1, GSTT1 and GSTP1 Ile105Val. Lung cancer risk associated with individual SNPs was seen for GSTP1 [A allele; odds ratio (OR) = 1.85; 95% confidence interval (CI), 1.04–3.27] and XRCC1 (A/A genotype; OR = 1.68; 95% CI, 1.01–2.79) in white women and CYP1B1 (G allele; OR = 11.1; 95% CI, 1.18–104) in black women smokers. White women smokers carrying two risk genotypes at the following loci were at increased risk of lung cancer compared with individuals not carrying risk alleles at these loci: CYP17 and GSTM1, COMT and GSTM1, CYP17 and GSTT1, XRCC1 and GSTP1, CYP1B1 and XRCC1 and COMT and XRCC1. The most parsimonious model of lung cancer risk in white smoking women included age, family history of lung cancer, history of chronic lung disease, pack-years, body mass index, XRCC1 A/A genotype, GSTM1 null and COMT A/G or G/G genotype. These findings support the need for continued study of estrogen in relation to lung cancer risk. Polymorphisms in the tobacco metabolism, estrogen metabolism and DNA repair pathways will be useful in developing more predictive models of individual risk.
Abbreviations: BMI, body mass index; CI, confidence interval; COMT, catechol-O-methyltransferase; CYP, cytochrome P450; ER, estrogen receptor; ETS, environmental tobacco smoke; GST, glutathione S-transferase; HRT, hormone replacement therapy; NSCLC, non-small cell lung cancer; OR, odds ratio; PCR, polymerase chain reaction; SNP, single-nucleotide polymorphism
Received August 20, 2008; revised January 20, 2009; accepted January 20, 2009.