Carcinogenesis Advance Access originally published online on August 1, 2008
Carcinogenesis 2008 29(10):1938-1943; doi:10.1093/carcin/bgn178
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Pathway-based evaluation of 380 candidate genes and lung cancer susceptibility suggests the importance of the cell cycle pathway
1 Occupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD 20892, USA
2 Department of Epidemiology and Public Health, Yale University School of Medicine, New Haven, CT 06520, USA
3 Chinese Center for Disease Control and Prevention, Beijing, China
* To whom correspondence should be addressed. Tel: +1 301 594 4649; Fax: +1 301 402 1819; Email: hosgoodd{at}mail.nih.gov
Common genetic variation may play an important role in altering lung cancer risk. We conducted a pathway-based candidate gene evaluation to identify genetic variations that may be associated with lung cancer in a population-based case–control study in Xuan Wei, China (122 cases and 111 controls). A total of 1260 single-nucleotide polymorphisms (SNPs) in 380 candidate genes for lung cancer were successfully genotyped and assigned to one of 10 pathways based on gene ontology. Logistic regression was used to assess the marginal effect of each SNP on lung cancer susceptibility. The minP test was used to identify statistically significant associations at the gene level. Important pathways were identified using a test of proportions and the rank truncated product methods. The cell cycle pathway was found as the most important pathway (P = 0.044) with four genes significantly associated with lung cancer (PLA2G6 minP = 0.001, CCNA2 minP = 0.006, GSK3β minP = 0.007 and EGF minP = 0.013), after adjusting for multiple comparisons. Interestingly, most cell cycle genes that were associated with lung cancer in this analysis were concentrated in the AKT signaling pathway, which is essential for regulation of cell cycle progression and cellular survival, and may be important in lung cancer etiology in Xuan Wei. These results should be viewed as exploratory until they are replicated in a larger study.
Abbreviations: AKT, v-akt murine thymoma viral oncogene homolog 1; FDR, false discovery rate; LD, linkage disequilibrium; SNP, single-nucleotide polymorphism
Received June 2, 2008; revised July 20, 2008; accepted July 25, 2008.
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