Breast cancer risk linked to genetic risk score

Women with high-risk scores for a number of common genetic variants are at a higher risk of breast cancer and estrogen receptor-positive disease, according to a study published in JAMA.

The study, conducted by Gillian Reeves, PhD, of the Cancer Epidemiology Unit, University of Oxford, U.K., and colleagues analyzed overall breast cancer risk by tumor subtype and a polygenic risk score. Included in the study were 10,306 women with breast cancer and 10,393 women without breast cancer who in 2005 to 2008 provided blood samples for genotyping. The researchers estimated the per-allele odds ratio for individual single-nucleotide polymorphisms (SNPs) and the cumulative incidence of breast cancer to age 70 years in relation to a polygenic risk score based on the 4, 7, or 10 SNPs most strongly associated with risk.

The results of the study revealed that the odds ratios for breast cancer were greatest for the SNPs FGFR2-rs2981582 and TNRC9-rs3803662 and, for these 2 SNPs, were significantly greater for estrogen receptor (ER)-positive than for ER-negative disease.

“Certain established risk factors for breast cancer have similar, or even greater, effects on breast cancer incidence than the differences seen here between women in the highest vs. the lowest fifth of polygenic risk score,” the authors concluded. “Furthermore, no interactions have been found between the effects of the genes investigated here and the other risk factors for breast cancer. Hence, as others have suggested, subdividing women on the basis of their polygenic risk is, at this stage, not a useful tool for population-based breast cancer screening programs but may be useful for understanding disease mechanisms.”

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