Dataset Information

Racial differences in the association between SNPs on 15q25.1, smoking behavior, and risk of non-small cell lung cancer.

ABSTRACT:

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.

SUBMITTER: Schwartz AG

PROVIDER: S-EPMC3768000 | biostudies-literature | 2009 Oct

REPOSITORIES: biostudies-literature

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Publications

Racial differences in the association between SNPs on 15q25.1, smoking behavior, and risk of non-small cell lung cancer.

Schwartz Ann G AG Cote Michele L ML Wenzlaff Angela S AS Land Susan S Amos Christopher I CI

Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer 20091001 10

<h4>Introduction</h4>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, ...[more]

PMID: 19641473

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Project description:BackgroundNon-smoking-related lung adenocarcinoma (LUAD) has its own characteristics. Genetic and microenvironmental differences in smoking and non-smoking LUAD patients were analyzed to elucidate the oncogenesis of non-smoking-related LUAD, which will improve our understanding of the underlying molecular mechanism and be of clinical use in the future.MethodsThe Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO) databases were used for clinical and genomic information. Various bioinformatics tools were used to analyze differences in somatic mutations, RNA and microRNA (miRNA) expression, immune infiltration, and stemness indices. GO, KEGG, and GSVA analyses were performed with R. A merged protein-protein interaction (PPI) network was constructed and analyzed. A miRNA-differentially expressed gene network was constructed with miRNet. qRT-PCR was used for validation of 4 most significantly differently expressed genes and 2 miRNAs in tumor samples obtained from 20 pairs of non-smoking and smoking patients.ResultsFive hundred and one patients with LUAD were obtained, including 210 in the non-smoking group and 292 in the smoking group. A total of 174 significantly altered somatic mutations were detected, including mutations in tumor protein p53 and epidermal growth factor receptor, which were downregulated in non-smoking-related LUAD. At the RNA level, 231 significantly differentially expressed genes were obtained; 124 were upregulated and 107 downregulated in the non-smoking group. GSVA analysis revealed 42 significant pathways. Other functional and enrichment analyses of somatic mutations and RNA expression levels revealed that these genes were significantly enriched in receptor activity regulation and receptor binding. Differences in microenvironments including immune infiltration (e.g., CD8+ T cells and resting mast cells) and stemness indices were also found between groups. A 79-pair interaction was found between differentially expressed genes and miRNAs, of which miR-335-5p and miR-34a-5p were located in the center. Twenty-one genes, including vitronectin, neurotensin, and neuronatin, were differentially expressed in both non-smoking LUAD patients and DMSO-treated A549 cells. And the different expression of neurotensin, neuronatin, trefoil factor family2, regenerating family member 4, miR-377-5p, miR-34a were verified with the same tendency in our own samples.ConclusionsNon-smoking LUAD patients, compared to smokers, have different characteristics in terms of somatic mutation, gene, and miRNA expression and the microenvironment, indicating a diverse mechanism of oncogenesis.

Dataset Information

Racial differences in the association between SNPs on 15q25.1, smoking behavior, and risk of non-small cell lung cancer.

Introduction

Methods

Results

Conclusions

Publications

Racial differences in the association between SNPs on 15q25.1, smoking behavior, and risk of non-small cell lung cancer.

Similar Datasets

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