Mol. Hum. Reprod. Advance Access originally published online on February 16, 2007
Molecular Human Reproduction 2007 13(4):231-236; doi:10.1093/molehr/gam004
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CYP17 genotype is associated with short menstrual cycles, early oral contraceptive use and BRCA mutation status in young healthy women
1 Department of Oncology 2 Department of Cancer Epidemiology, Clinical Sciences, Lund University, Lund, Sweden
3 To whom corresponding should be addressed at: Department of Oncology, Clinical Sciences, Lund University, Barngatan 2:1, SE-221 85 Lund, Sweden. Tel.: +46 46 17 76 19; Fax: +46 46 14 73 27; E-mail: helena.jernstrom{at}med.lu.se
The CYP17 gene is involved in steroid hormone metabolism and has been proposed as a low penetrance gene for breast cancer. We aimed to investigate the associations between the CYP17 genotype and breast cancer risk factors, such as age at menarche, menstrual cycle length, oral contraceptive (OC) use, and BRCA mutation status among 258 healthy young women, aged 
40, from 158 breast cancer high-risk families. Questionnaires including questions on reproductive factors and OC use were completed and blood samples were obtained from all women. CYP17 (rs743572) was genotyped with sequencing in 254 women. The main findings were that short menstrual cycles (<27 days) were significantly more common with increasing number of variant A2 alleles (8%, 17% and 32%; Ptrend = 0.002, adjusted for family clustering). Each A2 allele was associated with a 7 months earlier OC start (17.8, 17.0, and 16.6 years; Ptrend = 0.014, adjusted for age at menarche, ever-smoking and family clustering). Homozygosity for the A2 allele was more common among known non-carriers from BRCA1/2 families compared with other high-risk women OR 2.92 (95% CI 1.49–5.73; P = 0.002, adjusted for family clustering). We found no association between CYP17 genotype and age at menarche. In conclusion, this study suggests that short menstrual cycles, age at first OC use and BRCA mutation status may need to be considered in studies exploring the relationships between CYP17 and risk factors for early onset breast cancer.
Key words: BRCA1/2/breast cancer/menstrual cycle length/CYP17 polymorphism/oral contraceptives
Submitted on December 19, 2006; accepted on January 12, 2007.
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  P. Pasanisi, G. Hedelin, J. Berrino, J. Chang-Claude, S. Hermann, M. Steel, N. Haites, J. Hart, R. Peled, L. Gafa, et al. Oral Contraceptive Use and BRCA Penetrance: A Case-Only Study Cancer Epidemiol. Biomarkers Prev., July 1, 2009; 18(7): 2107 - 2113. [Abstract] [Full Text] [PDF]
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