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

Academic Article

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 Single Nucleotide Polymorphisms (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-value <10-7) or statistically significantly (p-value <5x10-8) 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. Additionally, understanding the role of genetics in fertility in childhood cancer survivors may be better approached using more advanced sequencing techniques.
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    Author List

  • Rotz SJ; Worley S; Hu B; Bazeley P; Baedke JL; Hudson MM; Kuo DJ; Oeffinger KC; Robison LL; Sahoo D