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CHRNA9 polymorphisms and smoking exposure synergize to increase the risk of breast cancer in Taiwan.

Authors :
Hsieh YC
Lee CH
Tu SH
Wu CH
Hung CS
Hsieh MC
Chuang CW
Ho YS
Chiou HY
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.)

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