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Does a polymorphism in the CYP17 gene predict mammographic density?
Breast Cancer Research volume 2, Article number: P7.03 (2000)
Mammographic density has been associated consistently with breast cancer risk in epidemiological studies. We and others have shown that hormonal status is associated with mammographic density. A pilot study was conducted to determine if a known polymorphism in a gene, CYP17, involved in the biosynthesis of female sex steroids, plays a role in mammographic density. The CYP17 gene encodes the cytochrome P450c17 enzyme which mediates the 17α -hydroxylation of pregnenolone and progesterone, and subsequent conversion of these 17-hydroxylated products to the estradiol precursors DHEA and androstenedione. In the 5' -UTR region of the CYP17 gene, a C/T single nucleotide polymorphism (SNP) results in two alleles designated A1 and A2. The A2 allele has been associated with higher circulating hormone levels in both premenopausal and postmenopausal women.
We used data from 94 breast cancer cases aged 40 to 64, diagnosed between 1994 and 1998, who participated in the Los Angeles part of the population-based Women's Contraceptive and Reproductive Experience (CARE) case-control study. We obtained blood samples from the cases, and scanned mammograms obtained prior to diagnosis (some as long as 5 years before). Mammographic density was determined using a method we have published previously. Subjects were genotyped for the CYP17 SNP using genomic DNA from blood.
The mean percent density in the three groups of women with the A1A1, A1A2 and A2A2 alleles were similar (25.4%, 25.3% and 29.3%). However, compared with women with the A1A1 genotype, the odds ratios (and 95% confidence intervals) of having a dense mammogram (>50% mammographic density) in women with the A1A2 or A2A2 genotype were 3.9 (0.8-19.3) and 5.6 (0.8-9.6) respectively, (P for trend = 0.09). The results suggest that CYP17 may be associated with mammographic density, possibly via its effect on estrogen levels.
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Ursin, G., Ingles, S., Spencer Feigelson, H. et al. Does a polymorphism in the CYP17 gene predict mammographic density?. Breast Cancer Res 2, P7.03 (2000) doi:10.1186/bcr171
- Breast Cancer
- Single Nucleotide Polymorphism
- Breast Cancer Risk
- Mammographic Density