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

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Rotz, SJ; Worley, S; Hu, B; Bazeley, P; Baedke, JL; Hudson, MM; Kuo, DJ; Oeffinger, KC; Robison, LL; Sahoo, D; Wang, F; Yasui, Y; Armstrong, GT; Bhatia, S

Published Date

  • September 2, 2022

Published In

Volume / Issue

  • 31 / 9

Start / End Page

  • 1858 - 1862

PubMed ID

  • 35700038

Pubmed Central ID

  • PMC9444932

Electronic International Standard Serial Number (EISSN)

  • 1538-7755

Digital Object Identifier (DOI)

  • 10.1158/1055-9965.EPI-22-0314


  • eng

Conference Location

  • United States