Estrogen-biosynthesis gene CYP17 and its interactions with reproductive, hormonal and lifestyle factors in breast cancer risk: results from the Long Island Breast Cancer Study Project.
The genes that are involved in estrogen biosynthesis, cellular binding and metabolism may contribute to breast cancer susceptibility. We examined the effect of the CYP17 promoter T --> C polymorphism and its interactions with the reproductive history, exogenous hormone use and selected lifestyle risk factors on breast cancer risk among 1037 population-based incident cases and 1096 population-based controls in the Long Island Breast Cancer Study Project. Overall, there were no associations between the CYP17 genotype and breast cancer risk. Among postmenopausal women, the joint exposure to higher body mass index (BMI) and the variant C allele was associated with an increased risk of breast cancer [odds ratio (OR), 1.60; 95% confidence interval (CI), 1.15-2.22]. The joint exposure to the variant C allele and long-term use of hormone replacement therapy (HRT) (>51 months) was related to an increased risk of breast cancer (OR, 1.51; 95% CI, 0.99-2.31) especially estrogen receptor-positive, progesterone receptor-positive breast cancer (OR, 1.87; 95% CI, 1.08-3.25). Among the control population, the CYP17 variant C allele was inversely associated with long-term use of postmenopausal HRT and a higher BMI in postmenopausal women. In conclusion, the findings suggest that the CYP17 variant C allele may increase breast cancer risk in conjunction with long-term HRT use and high BMI in postmenopausal women.
Chen
Yu
Y
Department of Environmental Medicine and New York University Cancer Institute, New York University School of Medicine, New York, NY 10016, USA.
Gammon
Marilie D
MD
Teitelbaum
Susan L
SL
Britton
Julie A
JA
Terry
Mary Beth
MB
Shantakumar
Sumitra
S
Eng
Sybil M
SM
Wang
Qiao
Q
Gurvich
Irina
I
Neugut
Alfred I
AI
Santella
Regina M
RM
Ahsan
Habibul
H
D015992:Body Mass Index; D001943:Breast Neoplasms / Q000453:epidemiology* / Q000235:genetics*; D015914:Estrogen Replacement Therapy; D004967:Estrogens / Q000096:biosynthesis*; D005260:Female; D005838:Genotype; D006801:Humans; D015994:Incidence; D008019:Life Style; D009518:New York / Q000453:epidemiology; D020641:Polymorphism, Single Nucleotide; D017698:Postmenopause; D011401:Promoter Regions, Genetic; D012307:Risk Factors; D013254:Steroid 17-alpha-Hydroxylase / Q000235:genetics*
D004967:Estrogens; D013254:Steroid 17-alpha-Hydroxylase