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Genetic risk score predicted disease type, breast cancer risk
Reeves GK. JAMA. 2010:304:426-434.
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Women with higher risk scores based on having certain single nucleotide polymorphisms were at greater risk for breast cancer, according to a recently published study. In addition, these risk scores also predicted whether women would have ER-positive disease.
Researchers conducted a study to analyze whether 14 individual SNPs were related to breast cancer risk overall and by tumor subtype. The study included 10,306 women with breast cancer and 10,393 women without breast cancer. All women had provided blood samples for genotyping to a U.K. study between 2005 and 2008. The researchers estimated the per-allele OR for individual SNPs.
Seven of the 14 SNPs were confirmed as having significant associations with overall breast cancer risk. The OR for breast cancer was greatest for FGFR2-rs2981582 and TNRC9-rs3803662. In addition, the OR for having ER-positive breast cancer vs. ER-negative breast cancer was also significantly higher for these two SNPs. For FGFR2-rs2981582, the OR for ER-positive disease was 1.30; for TNRC9-rs3803662, it was 1.24.
The researchers also identified a significant association between 2q-rs13387042 and bilateral vs. unilateral disease (OR=1.39) and lobular vs. ductal tumors (OR=1.35).
Finally, the researchers estimated the cumulative incidence of breast cancer to age 70 years in relation to a polygenic risk score based on the four, seven or 10 SNPs most strongly associated with risk. Based on the seven identified SNPs most strongly related to risk, women in the top fifth of the risk score had a cumulative incidence for breast cancer of 8.8% vs. 4.4% among women in the bottom fifth of the risk score.
When examining cumulative incidence for ER-positive disease, the risk score was 7.4% for the top fifth vs. 3.4% for the bottom fifth.
“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. Indeed, our estimate of the cumulative incidence of breast cancer to age 70 years in women in the top fifth for polygenic risk score (8.8%) is similar to that for women in developed countries with one first-degree relative with breast cancer (9.1%), and considerably less than that for women with two affected first-degree relatives (15.4%). 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,” the researchers conclude.
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