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.

Original languageEnglish
Pages (from-to)2520-2525
Number of pages6
JournalCarcinogenesis
Volume35
Issue number11
DOIs
Publication statusPublished - Nov 1 2014

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Taiwan
Smoking
Single Nucleotide Polymorphism
Breast Neoplasms
Cholinergic Receptors
Nicotine
Genes
Breast
Tobacco Smoke Pollution
Luciferases
Genetic Promoter Regions
Case-Control Studies
Carcinogenesis
Alleles
Odds Ratio
Genotype
Confidence Intervals
Neoplasms

ASJC Scopus subject areas

  • Medicine(all)

Cite this

CHRNA9 polymorphisms and smoking exposure synergize to increase the risk of breast cancer in Taiwan. / Hsieh, Yi Chen; Lee, Chia Hwa; Tu, Shih Hsin; Wu, Chih Hsiung; Hung, Chin Sheng; Hsieh, Mao Chih; Chuang, Ching Wen; Ho, Yuan Soon; Chiou, Hung Yi.

In: Carcinogenesis, Vol. 35, No. 11, 01.11.2014, p. 2520-2525.

Research output: Contribution to journalArticle

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AU - Chuang, Ching Wen

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AU - Chiou, Hung Yi

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