Deciphering the impact of common genetic variation on lung cancer risk: a genome-wide association study.
paper
Cited
Public
- Authors
- Broderick, Peter; Wang, Yufei; Vijayakrishnan, Jayaram; Matakidou, Athena; Spitz, Margaret R; Eisen, Timothy; Amos, Christopher I; Houlston, Richard S
- Year
- 2009
- Journal
- Cancer research
- PMID
- 19654303
- DOI
- 10.1158/0008-5472.CAN-09-0680
- PMCID
- PMC2754318
To explore the impact of common variation on the risk of developing lung cancer, we conducted a two-phase genome-wide association (GWA) study. In phase 1, we compared the genotypes of 511,919 tagging single nucleotide polymorphisms (SNP) in 1,952 cases and 1,438 controls; in phase 2, 30,568 SNPs were genotyped in 2,465 cases and 3,005 controls. SNP selection was based on best supported P values from phase 1 and two other GWA studies of lung cancer. In the combined analysis of phases 1 and 2, the strongest associations identified were defined by SNPs mapping to 15q25.1 (rs12914385; P = 3.19 x 10(-16)), 5p15.33 (rs4975616; P = 6.66 x 10(-7)), and 6p21.33 (rs3117582; P = 9.13 x 10(-7)). Variation at 15q25.1, but not 5p15.33 or 6p21.33, was strongly associated with smoking behavior with risk alleles correlated to higher consumption. Variation at 5p15.33 was shown to significantly influence induction of lung cancer histology. Pooling data from the four series provided 21,620 genotypes for 7,560 cases and 8,205 controls. A meta-analysis provided increased support that variation at 15q25.1 (rs8034191; P = 3.24 x 10(-26)), 5p15.33 (rs4975616; P = 2.99 x 10(-9)), and 6p21.33 (rs3117582; P = 4.46 x 10(-10)) influences lung cancer risk. The next best-supported associations were attained at 15q15.2 (rs748404: P = 1.08 x 10(-6)) and 10q23.31 (rs1926203; P = 1.28 x 10(-6)). These data indicate few common variants account for 1% of the excess familial risk underscoring the necessity of having additional large sample series for gene discovery.
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| Name | Type |
|---|---|
| 15q25.1 local | variant |
| 15q25 locus | variant |
| 1958 British Birth Cohort | cohort |
| 5p local | variant |
| 5p15.33 local | variant |
| 5p15.33 region local | variant |
| 6p local | variant |
| 6p21.33 local | variant |
| 6p21.33 region local | variant |
| adenocarcinoma local | phenotype |
| apoptosis | phenotype |
| BAT3 | gene |
| cases | cohort |
| Chrna3 | gene |
| Chrna4 | gene |
| CHRNA5 | gene |
| Chrnb4 | gene |
| cigarettes | phenotype |
| cis-platinum resistance local | phenotype |
| CLMPTL1 local | gene |
| CLPTM1L local | gene |
| colorectal cancer | phenotype |
| controls | cohort |
| EP300 | gene |
| European population | cohort |
| familial risk | cohort |
| GELCAPS local | cohort |
| genetic factors | cohort |
| Genetic Lung Cancer Predisposition Study local | cohort |
| HapMap CEU | cohort |
| heavy drinking | phenotype |
| IARC | cohort |
| IARC-GWA local | cohort |
| IARC-GWA study local | cohort |
| IREB2 | gene |
| light smokers | phenotype |
| LOC123688 | gene |
| low-frequency variant | variant |
| low penetrance variants local | variant |
| lung cancer | phenotype |
| lung cancer risk | phenotype |
| medium smoker local | phenotype |
| National Cancer Research Network genetic epidemiological studies local | cohort |
| National Study of Colorectal Cancer local | cohort |
| nicotine | drug |
| nicotine dependence | phenotype |
| non-small cell lung cancer | phenotype |
| NSCLC | phenotype |
| NSCLC adenocarcinoma local | phenotype |
| PAH adducts local | drug |
| Phase 1 | cohort |
| Phase 1 GWA local | cohort |
| Phase 2 | cohort |
| Phase 2 GWA local | cohort |
| PicoGreen local | drug |
| platinum local | drug |
| propensity to smoke | phenotype |
| PSMA4 | gene |
| Relatives of lung cancer cases local | cohort |
| Royal Marsden Hospital Trust/Institute of Cancer Research Family History and DNA Registry local | cohort |
| rs11264329 local | variant |
| rs1150752 local | variant |
| rs11853991 local | variant |
| rs12914385 | variant |
| rs2736100 local | variant |
| rs2844363 local | variant |
| rs3117582 local | variant |
| rs401681 local | variant |
| rs402710 local | variant |
| rs4975616 local | variant |
| rs504417 local | variant |
| rs748404 local | variant |
| rs8034191 | variant |
| rs8042374 local | variant |
| rs938682 local | variant |
| rs9838682 local | variant |
| SCLC local | phenotype |
| shorter telomere length local | phenotype |
| smoking | phenotype |
| smoking behaviour | phenotype |
| smoking-related carcinogens local | drug |
| SNP | cohort |
| squamous disease local | phenotype |
| telomere length | phenotype |
| TERT | gene |
| Texas local | cohort |
| Texas-GWA local | cohort |
| Texas GWA study local | cohort |
| Texas-GWA study local | cohort |
| TGM5 local | gene |
| TNXB local | gene |
| tobacco smoking behaviour local | phenotype |
| tobacco use | phenotype |
| TP53 | gene |
| Twin cohort | cohort |
| UK-GWA Phase 1 local | cohort |
| UK-GWA Phase 2 local | cohort |
| UK-GWA Phase 2 controls local | cohort |
| UK-GWA study local | cohort |
| UK-GWA study Phase 1 local | cohort |
| UK-GWA study Phase 2 local | cohort |
| UK study local | cohort |
| variant | cohort |
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