Carcinogenesis Advance Access published online on May 4, 2009
Carcinogenesis, doi:10.1093/carcin/bgp102
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CYP 450 polymorphisms as risk factors for early onset lung cancer: gender specific differences
1 Department of Epigenomics and Cancer Risk Factors
2 Department of Cancer Epidemiology, German Cancer Research Centre (DKFZ), Heidelberg, Germany
3 Institute of Epidemiology, Helmholtz Centre Munich, Germany
4 Department of Genetic Epidemiology, Georg-August University of Göttingen, Medical School, Germany
5 Heidelberg, Germany
6 Chair of Epidemiology, LMU Munich
To whom correspondence should be addressed: Angela Risch, German Cancer Research Center (DKFZ), Division C010, Epigenomics and Cancer Risk Factors, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany, Phone: +49-6221-42-4322, FAX: +49-6221-42-3359, e-mail: 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. 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.
13 polymorphisms in the CYP1A1, CYP1B1, CYP2A13, CYP3A4 and CYP3A5 genes were analysed. No significant association was found for any of the analysed 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, (OR 1.97; 95% 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.
Key Words: Cytochrome P450 • lung cancer • early onset • genetic polymorphisms • gender effect
Received December 19, 2008; revised April 13, 2009; accepted April 21, 2009.