Journal
CARCINOGENESIS
Volume 35, Issue 11, Pages 2520-2525Publisher
OXFORD UNIV PRESS
DOI: 10.1093/carcin/bgu179
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Funding
- Health and Welfare surcharge of tobacco products
- Ministry of Health and Wealth to the Comprehensive Cancer Center of Taipei Medical University [MOHW103-TD-B-111-01]
- National Science Council of Taiwan [NSC100-2632-B-038-001-MY3]
- Taipei Medical University [TMU102-AE1-B03]
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Previous studies indicated that smoking exposure is associated with an increased risk of breast cancer, and alpha 9-nicotine acetylcholine receptors (alpha 9-nAChRs) are involved in breast tumorigenesis. However, no studies have explored the joint effect of alpha 9-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 CHRAA9 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.
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