Single-nucleotide polymorphisms and breast cancer risk

January 01, 0001

Single-nucleotide polymorphisms and breast cancer risk

Despite advances in genetics, the genetic contribution to breast cancer risk remain relatively poorly understood outside of a few prominent mutations. These UK and French researchers analyzed breast cancer risk in relation to 14 individual single-nucleotide polymorphisms (SNPs) previously linked to the disease, and in relation to a polygenic risk score. They used data from 10 306 women with breast cancer and 10 393 women without breast cancer who in 2005-2008 in a large prospective study of UK women. They also performed a meta-analysis of these results and of other published data.

The researchers found: "Odds ratios (ORs) for breast cancer were greatest for FGFR2-rs2981582 and TNRC9-rs3803662 and, for these 2 SNPs, were significantly greater for estrogen receptor (ER)-positive than for ER-negative disease, both in our data and in meta-analyses of all published data (pooled per-allele ORs for ER-positive vs ER-negative disease: 1.30 vs 1.05 for FGFR2, and 1.24 vs 1.12 for TNRC9). The next strongest association was for 2q-rs13387042, for which the per-allele OR was significantly greater for bilateral than unilateral disease (1.39 vs 1.15) and for lobular than ductal tumors (1.35 vs 1.10). The estimated cumulative incidence of breast cancer to age 70 years among women in the top and bottom fifths of a polygenic risk score based on 7 SNPs was 8.8% and 4.4%, respectively. For ER-positive disease the corresponding risks were 7.4% and 3.4%, respectively, while for ER- negative disease they were 1.4% and 1.0%. The findings did not differ materially according to the number of SNPs included in the polygenic risk model."

The researchers concluded: "The polygenic risk score was substantially more predictive of ER-positive than of ER-negative breast cancer, particularly for absolute risk."

This study begins to shed light on the genetic risk involving SNPs and different breast cancer subtypes

For the full abstract, click here.

JAMA 304(4): 426-434, 28 July 2010
© 2010 American Medical Association
Incidence of Breast Cancer and Its Subtypes in Relation to Individual and Multiple Low-Penetrance Genetic Susceptibility Loci. Gillian K. Reeves, Ruth C. Travis, Jane Green, et al.

Category: X. Female Genital System, Breast. Keywords: breast cancer, single nucleotide polymorphisms, SNPs, polygenic risk, estrogen receptor, prospective study and meta-analysis, journal watch.
Synopsis edited by Dr Paul Schaefer, Toledo, Ohio. Posted on Global Family Doctor 3 September 2010

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