Carcinogenesis Advance Access published online on February 6, 2008
Carcinogenesis, doi:10.1093/carcin/bgn020
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
A comprehensive analysis of phase I and phase II metabolism gene polymorphisms and risk of non-small cell lung cancer in smokers
1 Section of Toxicology, Department of Biological and Chemical Working Environment, National Institute of Occupational Health, Oslo, Norway
2 Department of Genetic Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany
3 Department of Biology, University of Pisa, Pisa, Italy
4 Haukeland University Hospital, Bergen, Norway
* To whom correspondence should be addressed: Tel: +47 23195284; Fax: +47 23195203; Email: shan.zienolddiny{at}stami.no.
Lung cancer is a leading cause of cancer mortality worldwide with smoking and occupational exposure to carcinogenic compounds as the major risk factors. Susceptibility to lung cancer is affected by existence of polymorphic genes controlling the levels of metabolic activation and detoxification of carcinogens. We have investigated 105 single nucleotide polymorphisms (SNPs) in 31 genes from the Phase I and Phase II metabolism genes and antioxidant defence genes for association with risk of non-small cell lung cancer (NSCLC) in a Norwegian population-based study. Our results indicate that several SNPs in the Phase I genes CYP1B1, CYP2D6, CYP2E1 and CYP3A4, are associated with risk of NSCLC. Moreover, significant associations with multiple SNPs in the Phase II genes ALDH2, COMT, EPHX1, SOD2, NAT1, NAT2, GSTM3, GSTP1, GSTT2 and MPO were also found. We prioritized our findings by use of two different recently developed Bayesian statistical tools, employing conservative prior probabilities of association. When we corrected for multiple testing using these statistical tools, three novel associations of NSCLC risk with SNPs in the CYP1B1 (Arg48Gly), COMT (Val158Met) and GSTT2 (Met139Ile) genes were found noteworthy. However, only four of the previously reported associations with polymorphisms in the GSTP1 (Ala14Val), SOD2 (Val16Ala), EPHX1 (His139Arg) genes and the NAT1 fast acetylator phenotype remained significantly associated with lung cancer.
Key Words: Lung cancer • single nucleotide polymorphism (SNP) • metabolism • CYP450
These authors contributed equally to the manuscript. Received September 12, 2007; revised December 21, 2007; accepted January 14, 2007.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  S. Zienolddiny, V. Skaug, N. E. Landvik, D. Ryberg, D. H. Phillips, R. Houlston, and A. Haugen The TERT-CLPTM1L lung cancer susceptibility variant associates with higher DNA adduct formation in the lung Carcinogenesis, August 1, 2009; 30(8): 1368 - 1371. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. E. Landvik, K. Hart, V. Skaug, L. B. Stangeland, A. Haugen, and S. Zienolddiny A specific interleukin-1B haplotype correlates with high levels of IL1B mRNA in the lung and increased risk of non-small cell lung cancer Carcinogenesis, July 1, 2009; 30(7): 1186 - 1192. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. L. Cote, W. Yoo, A. S. Wenzlaff, G. M. Prysak, S. K. Santer, G. B. Claeys, A. L. Van Dyke, S. J. Land, and A. G. Schwartz Tobacco and estrogen metabolic polymorphisms and risk of non-small cell lung cancer in women Carcinogenesis, April 1, 2009; 30(4): 626 - 635. [Abstract] [Full Text] [PDF]
|
|