A comprehensive examination of CYP19 variation and risk of breast cancer using two haplotype-tagging approaches.

Breast Cancer Res Treat 2007 Apr 27;102(2):237-47. Epub 2006 Sep 27.

Department of Health Sciences Research, Division of Epidemiology, Mayo Clinic College of Medicine, Rochester, MN 55901, USA.

Background: Numerous studies point to a positive relationship between elevated levels of estrogens and increased risk of breast. Androgens are converted to estrogens by the aromatase enzyme, which is encoded by the CYP19 gene. We recently published resequencing data on 88 polymorphisms identified in that gene. The hypothesis tested in this study was that polymorphisms, or haplotypes, in CYP19 are related to risk of breast cancer.

Methods: Incident cases of breast cancer were identified through the Division of Medical Oncology at the Mayo Clinic in Rochester, MN. Controls were patients visiting Mayo for an annual medical examination. Controls were frequency matched to cases based on age and region of residence. Tag-polymorphisms were selected using 2 methods: (1) 12 variants using the tag-selection method of Carlson et al. (Am J Hum Genet 74:106-120, 2004); and (2) 12 variants using the haplotype method of Stram (Genet Epidemiol 27:365-374, 2004). Six SNPs were selected by both methods. Genotyping was conducted using SNPStream, TaqMan and RFLP analyses. Logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals (CI). Analyses were conducted among all cases and controls, or stratified by estrogen receptor alpha (ER) status and/or menopausal status.

Results: A total of 750 cases (60% postmenopausal) and 732 controls (75% postmenopausal) were included. No association with breast cancer risk was detected for individual variants, selected tagSNPs or hap-tag SNPs despite 80% power to detect OR as low as 1.49 for minor allele frequency (MAF) of 0.10. Similarly, stratified analyses based on ER status or menopausal status failed to detect any association with breast cancer risk.

Conclusion: These analyses suggest that variants of CYP19 are not associated with risk of breast cancer.

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10549-006-9324-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2868324PMC
April 2007
2 Reads

Publication Analysis

Top Keywords

breast cancer
20
risk breast
16
selected methods
8
association breast
8
breast
7
risk
5
cancer
5
method carlson
4
carlson hum
4
tagsnps hap-tag
4
methods variants
4
variants
4
hap-tag snps
4
variants tag-selection
4
tag-selection method
4
hum genet
4
2004 variants
4
method stram
4
stram genet
4
individual variants
4

References

(Supplied by CrossRef)
Article in N Engl J Med
JD Yager et al.
N Engl J Med 2006
Article in N Engl J Med
M Clemons et al.
N Engl J Med 2001
Article in J Natl Cancer Inst
TJ Key et al.
J Natl Cancer Inst 2003
Article in J Natl Cancer Inst
B Rosner et al.
J Natl Cancer Inst 1996
Article in Am J Epidemiol
RS Paffenbarger Jr et al.
Am J Epidemiol 1980
Article in J Steroid Biochem Mol Biol
JN Ingle et al.
J Steroid Biochem Mol Biol 2005
Article in Clin Cancer Res
JN Ingle et al.
Clin Cancer Res 2006
Article in Pharmacogenetics
VN Kristensen et al.
Pharmacogenetics 1998
Article in Int J Cancer
CA Haiman et al.
Int J Cancer 2000
Article in Br J Cancer
N Siegelmann-Danieli et al.
Br J Cancer 1999

Similar Publications