Association of breast cancer risk with a common functional polymorphism (Asp327Asn) in the sex hormone-binding globulin gene.
Sex hormones play a central role in the development of breast cancer. Sex hormone-binding globulin (SHBG) modulates the bioavailability of circulating sex hormones and regulates their signaling system in the breast tissue. We evaluated the association of a common functional polymorphism (Asp327Asn) in the SHBG gene with breast cancer risk in a population-based case-control study (1,106 cases and 1,180 controls) conducted in Shanghai, China. The variant Asn allele was associated with a reduced breast cancer risk in postmenopausal women [odds ratio (OR), 0.73; 95% confidence interval (95% CI), 0.53-0.99], but not in premenopausal women (OR, 1.03; 95% CI, 0.82-1.27). The protective association was much stronger in postmenopausal women with a low body mass index (BMI; OR, 0.46; 95% CI, 0.29-0.75) or waist-to-hip ratio (OR, 0.51; 95% CI, 0.32-0.83) than those with a high BMI or waist-to-hip ratio (P for interaction < 0.05). Furthermore, the association was stronger for estrogen receptor-positive (OR, 0.64; 95% CI, 0.42-0.98) than for estrogen receptor-negative breast cancer (OR, 0.85; 95% CI, 0.50-1.45). Among postmenopausal controls, blood SHBG levels were 10% higher in carriers of the variant Asn allele than noncarriers (P = 0.06). Postmenopausal control women with the Asn allele and low BMI or waist-to-hip ratio had 20% higher SHBG levels (P < 0.05). This study suggests that the Asn allele in the SHBG gene may be related to a reduced risk of breast cancer among postmenopausal women by increasing their blood SHBG levels.
Cui
Yong
Y
Vanderbilt University Center for Health Services Research, 6th Floor, Medical Center East, Nashville, TN 37232-8300, USA.
Shu
Xiao-Ou
XO
Cai
Qiuyin
Q
Jin
Fan
F
Cheng
Jia-Rong
JR
Cai
Hui
H
Gao
Yu-Tang
YT
Zheng
Wei
W
D000328:Adult; D000368:Aged; D015992:Body Mass Index; D001943:Breast Neoplasms / Q000453:epidemiology / Q000235:genetics*; D016022:Case-Control Studies; D002681:China / Q000453:epidemiology; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D017698:Postmenopause; D017697:Premenopause; D011960:Receptors, Estrogen / Q000235:genetics; D012042:Registries; D012307:Risk Factors; D012738:Sex Hormone-Binding Globulin / Q000032:analysis / Q000235:genetics*
D011960:Receptors, Estrogen; D012738:Sex Hormone-Binding Globulin