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CHRNA9 polymorphisms and smoking exposure synergize to increase the risk of breast cancer in Taiwan.
- Source :
-
Carcinogenesis [Carcinogenesis] 2014 Nov; Vol. 35 (11), pp. 2520-5. Date of Electronic Publication: 2014 Aug 20. - Publication Year :
- 2014
-
Abstract
- Previous studies indicated that smoking exposure is associated with an increased risk of breast cancer, and α9-nicotine acetylcholine receptors (α9-nAChRs) are involved in breast tumorigenesis. However, no studies have explored the joint effect of α9-nAChRs (CHRNA9) genes and cigarette smoking exposure on breast cancer risk. A case-control study was conducted on 737 breast cancer patients and 719 age-matched healthy controls. Three single-nucleotide polymorphisms (SNPs) of CHRNA9 located in the promoter region were genotyped and compared between cases and controls to identify those SNPs associated with breast cancer susceptibility. A dual-luciferase reporter assay was used to analyze the promoter activities of these SNPs of the CHRNA9 gene. After a Bonferroni correction, the G allele of the CHRNA9 rs7329797 SNP was significantly associated with an increased risk of developing breast cancer compared with A/A genotype carriers (odds ratio, 1.8; 95% confidence interval, 1.2-2.6). A multiplicative interaction between passive smoking exposure and the CHRNA9 rs73229797 SNP on the risk of breast malignancy was observed. A functional assay further showed that rs73229797 was associated with increased promoter activity of the CHRNA9 gene. Our findings support a significant interaction effect existing between the CHRNA9 gene and smoking exposure on the risk of breast cancer development.<br /> (© The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)
- Subjects :
- Adult
Aged
Breast Neoplasms epidemiology
Breast Neoplasms pathology
Female
Genetic Predisposition to Disease
Humans
Middle Aged
Polymorphism, Single Nucleotide
Promoter Regions, Genetic
Risk Factors
Smoking adverse effects
Taiwan
Breast Neoplasms genetics
Genetic Association Studies
Receptors, Nicotinic genetics
Smoking genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1460-2180
- Volume :
- 35
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- Carcinogenesis
- Publication Type :
- Academic Journal
- Accession number :
- 25142973
- Full Text :
- https://doi.org/10.1093/carcin/bgu179