Higher scores especially predictive of estrogen receptor-positive disease

-- Monica Smith

Tuesday, July 27, 2010 (Last Updated: 07/28/2010)

TUESDAY, July 27 (HealthDay News) -- Higher risk scores for breast cancer based on genetic variants linked to breast cancer are associated with a higher risk for cancer and are especially predictive of estrogen receptor (ER)-positive disease, according to research published in the July 28 issue of the Journal of the American Medical Association.

Gillian K. Reeves, Ph.D., of the University of Oxford in the United Kingdom, and colleagues genotyped blood samples from 10,306 women with and 10,393 women without breast cancer, and also analyzed data from other studies, to project cancer risk as it relates to 14 single-nucleotide polymorphisms (SNPs) with known links to breast cancer, and in relation to a polygenic risk score.

In both their study and their meta-analysis of published studies, the researchers found that the odds ratios for breast cancer -- significantly more so for ER-positive than ER-negative disease -- were highest with two specific SNPs, FGFR2-rs2981582 and TNRC9-rs3803662. The SNP 2q-rs13387042 had the next strongest association, significantly higher for bilateral than unilateral disease, and for lobular rather than ductal cancers. For women in the top and bottom fifths of a polygenic risk score based on seven SNPs, the estimated cumulative incidence of breast cancer by age 70 was 8.8 and 4.4 percent, respectively.

"The polygenic risk score was substantially more predictive of ER-positive than of ER-negative breast cancer, particularly for absolute risk," the authors conclude.

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Specialties Hematology & Oncology

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