Racial differences in the association between SNPs on 15q25.1, smoking behavior, and risk of non-small cell lung cancer.
- Authors
- Schwartz, Ann G; Cote, Michele L; Wenzlaff, Angela S; Land, Susan; Amos, Christopher I
- Year
- 2009
- Journal
- Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer
- PMID
- 19641473
- DOI
- 10.1097/JTO.0b013e3181b244ef
- PMCID
- PMC3768000
INTRODUCTION: Three genome-wide association studies identified a region on chromosome 15q25.1 associated with lung cancer and measures of nicotine addiction. This region includes nicotinic acetylcholine receptor subunit genes CHRNA3 and CHRNA5. These studies were conducted in European or European American populations and do not provide risk estimates for African Americans. The goal of this study was to determine whether recently identified genetic variation in 3 SNPs (rs1051730, rs931794, rs8034191) on chromosome 15q25.1 contributes to risk of lung cancer in African Americans. METHODS: Data were derived from three case-control studies. Participants included 1058 population-based non-small cell lung cancer cases selected from the Detroit area SEER registry and 1314 controls matched within study by age, race, and sex. Thirty-nine percent of participants were African American. RESULTS: Risk associated with rs1051730 (odds ratio 1.59; 95% confidence interval 1.16-2.19) and rs931794 (odds ratio 1.39; 95% confidence interval 1.09-1.78) increased in ever smoking African Americans adjusting for cigarettes smoked per day. Among white cases, the number of cigarettes smoked varied by genotype at all three SNPs, and when smoking quantity was included in the models, risk was not significantly associated with any of the three SNPs. CONCLUSIONS: These findings suggest that SNPs in the CHRNA3 and CHRNA5 region contribute to lung cancer risk, and while variant alleles are less frequent in African Americans, risk in this group may be greater than in whites and less likely to reflect an indirect effect on lung cancer risk through nicotine dependence.
A, LD structure at 15q25 in individuals of European ancestry. Boxes are shaded according to r2 values derived in Haploview (v3.2). Triangular border areas denote haplotype blocks assigned according to the method of Gabriel et al.23 B, LD structure at 15q25 in Yorubans. Boxes are shaded according to r2 values derived in Haploview (v3.2). Triangular border areas denote haplotype blocks assigned according to the method of Gabriel et al.23
LLM interpretation
This figure consists of two linkage disequilibrium (LD) plots (A and B) for the 15q25 genomic region in individuals of European ancestry and Yorubans, respectively. The visualizations use shaded boxes to represent $r^2$ values and triangular borders to delineate haplotype blocks. Comparison between the two plots shows a higher density of dark-shaded boxes and larger haplotype blocks in the European ancestry group (A) compared to the Yoruban group (B). Specific SNPs, including rs8031491, rs931794, and rs1051730, are labeled across both panels.
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