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 language | English |
|---|---|
| Pages (from-to) | 2520-2525 |
| Number of pages | 6 |
| Journal | Carcinogenesis |
| Volume | 35 |
| Issue number | 11 |
| DOIs | |
| Publication status | Published - Nov 1 2014 |
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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 journal › Article
}
TY - JOUR
T1 - CHRNA9 polymorphisms and smoking exposure synergize to increase the risk of breast cancer in Taiwan
AU - Hsieh, Yi Chen
AU - Lee, Chia Hwa
AU - Tu, Shih Hsin
AU - Wu, Chih Hsiung
AU - Hung, Chin Sheng
AU - Hsieh, Mao Chih
AU - Chuang, Ching Wen
AU - Ho, Yuan Soon
AU - Chiou, Hung Yi
PY - 2014/11/1
Y1 - 2014/11/1
N2 - 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.
AB - 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.
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U2 - 10.1093/carcin/bgu179
DO - 10.1093/carcin/bgu179
M3 - Article
VL - 35
SP - 2520
EP - 2525
JO - Carcinogenesis
JF - Carcinogenesis
SN - 0143-3334
IS - 11
ER -