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Genome-Wide Association Study of Pregnancy in Childhood Cancer Survivors: A Report from the Childhood Cancer Survivor Study

Year: 2022
Type: article
Study design: Observational Study
Abstract: BACKGROUND: Gonadotoxic treatment-related infertility has a significant impact on quality of life in childhood cancer survivors. Genome-wide association analyses to delineate the risk of infertility in childhood cancer survivors have not been previously reported. METHODS: Leveraging genotype data from a large survivor cohort, the Childhood Cancer Survivor Study (CCSS), we investigated the role of SNPs on future pregnancy or siring a pregnancy in survivors without pelvic, testicular, or brain radiation who had ever been married. We calculated sex-stratified hazard ratios, using Cox proportional hazards modeling, adjusting for birth cohort (before 1965 vs. 1965 or later) and doses of relevant chemotherapies; replication was attempted in the independent St. Jude Lifetime Cohort study (SJLIFE). RESULTS: In the CCSS cohort, nine SNPs were found to be suggestive (P < 10-7) or statistically significantly (P < 5 × 10-8) associated with pregnancy, however, none of the SNPs were replicated in SJLIFE. Cohorts differed based on the overall pregnancy rate, frequency of sterilizing procedures, and birth cohort. CONCLUSIONS: We were not able to replicate our findings of SNPs associated with pregnancy in childhood cancer survivors. IMPACT: Future attempts at replication should be considered in cohorts treated in a comparable era. In addition, understanding the role of genetics in fertility in childhood cancer survivors may be better approached using more advanced sequencing techniques.
DOI: 10.1158/1055-9965.epi-22-0314
Authors: Seth J. Rotz, Sarah Worley, Bo Hu, Peter Bazeley, Jessica L. Baedke, Melissa M. Hudson, Dennis J. Kuo, Kevin C. Oeffinger, Leslie L. Robison, Debashis Sahoo, Fan Wang, Yutaka Yasui, Gregory T. Armstrong, Smita Bhatia
Institutions: Cleveland Clinic, St. Jude Children's Research Hospital, University of California San Diego, Duke University, Duke Medical Center, University of Alabama at Birmingham
Language: English
Field: Medicine
Open Access status: bronze
Funders: St. Jude Children's Research Hospital, American Lebanese Syrian Associated Charities, National Institutes of Health, National Cancer Institute, National Institute of General Medical Sciences, National Institute of Allergy and Infectious Diseases, National Center for Advancing Translational Sciences
Awards: G1045630917, G110462897, Macrophage Polarization in Response to Infections and Inflammation, G2242390953, G2279630131, G290472089, G3272408970, G3529129531, G4444553339, G4763367995, G5442089819, The St. Jude Lifetime Cohort, G609259107, G687732040, G7390770887, G751896108, G7630955548, G865138149, Cancer Center Support Grant (CCSG)
OpenAlex ID: W4282823301
FWCI: 0.398
Cites: 8
Cited by: 2
Related to: 10