Genetic Study Identifies Susceptibility Loci Modifying Risk for Breast Cancer After Radiation Therapy for Childhood Cancer

Key Points

  • Subsequent breast cancer risk was associated with rs4342822 on 1q41 and rs74949440 on 11q23 in patients receiving ≥ 10 Gy.
  • Risk was also associated with rs17020562 on 1q32.3 in patients receiving < 10 Gy.

As reported in the Journal of the National Cancer Institute, Morton et al have identified gene loci associated with radiation-related risk of breast cancer in survivors of childhood cancer.

Study Details

The study was a genome-wide association study of breast cancer in female survivors of childhood cancer involving two cohorts with data on long-term follow-up: the Childhood Cancer Survivor Study and St. Jude Lifetime Cohort. In the pooled population, 207 survivors had developed breast cancer, and 2,774 had not developed any subsequent neoplasm as of last follow-up. Genotyping and subsequent imputation yielded 16, 958, 466 high-quality variants for analysis. Associations were evaluated in the overall population and according to whether patients had received < 10 or ≥ 10 Gy breast radiation exposure.

Associations

Among survivors who received ≥ 10 Gy, the rs4342822 locus on 1q41 (nearest gene = PROX1) was associated with a subsequent breast cancer risk (risk allele frequency in control subjects [RAF controls] = 0.46, hazard ratio = 1.92, P = 7.09 × 10-9). Two rare variants also showed potential associations with an increased risk: among survivors who received ≥ 10 Gy, the rs74949440 locus on 11q23 (nearest gene = TAGLN), with RAF controls = 0.02 (P = 5.84 × 10-8; and in patients receiving < 10 gray, the rs17020562 locus on 1q32.3 (nearest gene = RPS6KC1), with RAF controls = 0.0005 (P = 6.68 × 10-8). Gene associations were observed only for the radiation dose subgroups, and findings were consistent in the two cohorts.

The investigators concluded: “Our study provides strong evidence that germline genetics outside high-risk syndromes could modify the effect of radiation exposure on breast cancer risk after childhood cancer.”

The study was supported by the National Cancer Institute.

Lindsay M. Morton, PhD, of the National Cancer Institute, is the corresponding author of the Journal of the National Cancer Institute article.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®. 


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