ArticleClinical cancer research : an official journal of the American Association for Cancer Research2018
Polygenic Determinants for Subsequent Breast Cancer Risk in Survivors of Childhood Cancer: The St Jude Lifetime Cohort Study (SJLIFE).
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
15 citing papers in PubMed, 27 citations in OpenAlex.
- Influence of treatment, genetic predisposition, and lifestyle on cardiovascular risk factors among cancer survivors.Journal of the National Cancer Institute · 2026Article
- Germline rare variants in cancer susceptibility genes and subsequent neoplasm risk after childhood cancer.Journal of the National Cancer Institute · 2025Article
- Genetic and epigenetic bases of long-term adverse effects of childhood cancer therapy.Nature reviews. Cancer · 2025Review
- Polygenic risk scores, radiation treatment exposures and subsequent cancer risk in childhood cancer survivors.Nature medicine · 2024Article
- Improving quality and quantity of life for childhood cancer survivors globally in the twenty-first century.Nature reviews. Clinical oncology · 2023Review
- Polygenic Risk and Chemotherapy-Related Subsequent Malignancies in Childhood Cancer Survivors: A Childhood Cancer Survivor Study and St Jude Lifetime Cohort Study Report.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2023Article
- Distinct DNA methylation signatures associated with blood lipids as exposures or outcomes among survivors of childhood cancer: a report from the St. Jude lifetime cohort.Clinical epigenetics · 2023Article
- Germline risk factors for second malignant neoplasms after treatment for pediatric hematologic malignancies.Hematology. American Society of Hematology. Education Program · 2022Article
- Leveraging Therapy-Specific Polygenic Risk Scores to Predict Restrictive Lung Defects in Childhood Cancer Survivors.Cancer research · 2022Article
- Polygenic Risk Score Improves Risk Stratification and Prediction of Subsequent Thyroid Cancer after Childhood Cancer.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2021Article
- Generalizability of "GWAS Hits" in Clinical Populations: Lessons from Childhood Cancer Survivors.American journal of human genetics · 2020Article
- Clinical applications of polygenic breast cancer risk: a critical review and perspectives of an emerging field.Breast cancer research : BCR · 2020Review
- Subsequent Neoplasm Risk Associated With Rare Variants in DNA Damage Response and Clinical Radiation Sensitivity Syndrome Genes in the Childhood Cancer Survivor Study.JCO precision oncology · 2020Article
- A pediatric perspective on genomics and prevention in the twenty-first century.Pediatric research · 2020Review
- Subsequent Breast Cancer in Female Childhood Cancer Survivors in the St Jude Lifetime Cohort Study (SJLIFE).Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2019Article
Corrections and comments
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Authors and funding
19 authors at 3 institutions in 2 countries.
Funding
Abstract
purposeThe risk of subsequent breast cancer among female childhood cancer survivors is markedly elevated. We aimed to determine genetic contributions to this risk, focusing on polygenic determinants implicated in breast cancer susceptibility in the general population. EXPERIMENTAL
designWhole-genome sequencing (30×) was performed on survivors in the St Jude Lifetime Cohort, and germline mutations in breast cancer predisposition genes were classified for pathogenicity. A polygenic risk score (PRS) was constructed for each survivor using 170 established common risk variants. Relative rate (RR) and 95% confidence interval (95% CI) of subsequent breast cancer incidence were estimated using multivariable piecewise exponential regression.
resultsThe analysis included 1,133 female survivors of European ancestry (median age at last follow-up = 35.4 years; range, 8.4-67.4), of whom 47 were diagnosed with one or more subsequent breast cancers (median age at subsequent breast cancer = 40.3 years; range, 24.5-53.0). Adjusting for attained age, age at primary diagnosis, chest irradiation, doses of alkylating agents and anthracyclines, and genotype eigenvectors, RRs for survivors with PRS in the highest versus lowest quintiles were 2.7 (95% CI, 1.0-7.3), 3.0 (95% CI, 1.1-8.1), and 2.4 (95% CI, 0.1-81.1) for all survivors and survivors with and without chest irradiation, respectively. Similar associations were observed after excluding carriers of pathogenic/likely pathogenic mutations in breast cancer predisposition genes. Notably, the PRS was associated with the subsequent breast cancer rate under the age of 45 years (RR = 3.2; 95% CI, 1.2-8.3).
conclusionsGenetic profiles comprised of small-effect common variants and large-effect predisposing mutations can inform personalized breast cancer risk and surveillance/intervention in female childhood cancer survivors.
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