Carcinogenesis Advance Access originally published online on May 4, 2009
Carcinogenesis 2009 30(7):1161-1169; doi:10.1093/carcin/bgp102
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CYP450 polymorphisms as risk factors for early-onset lung cancer: gender-specific differences
Department of Epigenomics and Cancer Risk Factors
1 Department of Cancer Epidemiology, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany
2 Institute of Epidemiology, Helmholtz Centre, 85764 Munich, Germany
3 Department of Genetic Epidemiology, Georg-August University of Göttingen, Medical School, 37073 Göttingen, Germany
4 Thoraxklinik, 69126 Heidelberg, Germany
5 Chair of Epidemiology, Ludwig-Maximilians-University, 80539 Munich, Germany
* To whom correspondence should be addressed. Department of Epigenomics and Cancer Risk Factors (C010), German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany. Tel: +49 6221 42 4322; Fax: +49 6221 42 3359; Email: a.risch{at}dkfz.de
Cytochrome P450 (CYP) enzymes, involved in metabolism of tobacco carcinogens, are also involved in estrogen metabolism and many are regulated by estrogens. These genes may thus be of relevance to gender-specific differences in lung cancer risk, particularly in early-onset lung cancer, where a high proportion of women is observed. We conducted a case–control study to investigate genetic polymorphisms in cytochromes that might modify the risk of developing early-onset lung cancer. In total, 638 Caucasian patients under the age of 51 with primary lung cancer and 1300 cancer-free control individuals, matched by age and sex, were included in this analysis. Thirteen polymorphisms in the CYP1A1, CYP1B1, CYP2A13, CYP3A4 and CYP3A5 genes were analyzed. No significant association was found for any of the analyzed polymorphisms and lung cancer risk overall. However, among women, a significantly increased risk of early-onset lung cancer was observed for carriers of the minor allele of CYP1B1 SNP rs1056836 [odds ratio (OR) 1.97; 95% confidence interval (CI) 1.32–2.94; P < 0.001]. Also, a non-significant increase in lung cancer risk was observed in the group of women carriers of the minor allele of CYP2A13 SNP rs1709084 (OR 1.64; 95% CI 1.00–2.70; P = 0.05). The effect of these two polymorphisms was shown to be modified by smoking. Haplotype analysis was performed for CYP1B1 and CYP2A13. No differences between cases and controls were observed for both genes (P = 0.63 and P = 0.42 for CYP1B1 and CYP2A13, respectively). Our results suggest that the CYP1B1 and the CYP2A13 genotypes may contribute to individual susceptibility to early-onset lung cancer in women.
Abbreviations: CI, confidence interval; CYP, cytochrome P450; HWE, Hardy–Weinberg equilibrium; KORA, Kooperative Gesundheitsforschung in der Region Augsburg; LUCY, Lung Cancer in the Young; NSCLC, non-small-cell lung cancer; OR, odds ratio; PY, pack-year; SCLC, small-cell lung cancer; SNP, single-nucleotide polymorphism
Received December 19, 2008; revised April 13, 2009; accepted April 21, 2009.