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Genetic Risk Score IDs Breast CA Risk in Female Child CA Survivors

Survivors in highest quintile of polygenic risk score have increased relative rate of breast cancer

WEDNESDAY, Oct. 31, 2018 (HealthDay News) — A polygenic risk score (PRS) can identify subsequent breast cancer risk among childhood survivors of cancer, according to a study published online Oct. 26 in Clinical Cancer Research.

Zhaoming Wang, Ph.D., from St. Jude Children’s Research Hospital in Memphis, Tennessee, and colleagues performed whole-genome sequencing on survivors in the St. Jude Lifetime Cohort and classified germline mutations in breast cancer predisposition genes for pathogenicity. For each survivor, a PRS was constructed using 170 established common risk variants.

A total of 1,133 female survivors of European ancestry were included in the analysis, and 47 of them were diagnosed with one or more subsequent breast cancers. The researchers found that for survivors in the highest versus the lowest quintiles of PRS, the relative rates were 2.7 (95 percent confidence interval [CI], 1 to 7.3; P = 0.05), 3 (95 percent CI, 1.1 to 8.1; P = 0.03), and 2.4 (95 percent CI, 0.1 to 81.1; P = 0.62) for all survivors and for survivors with and without chest irradiation, respectively, after adjustment for confounding variables. After the researchers excluded carriers of pathogenic/likely pathogenic mutations in breast cancer predisposition genes, similar associations were observed. The PRS was correlated with the subsequent breast cancer rate under the age of 45 years (RR, 3.2; 95 percent CI, 1.2 to 8.3; P = 0.02).

“This method can be utilized in the clinical setting to enhance the identification of high-risk survivors to enable the early detection and potential prevention of subsequent breast cancer,” Wang said in a statement.

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