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

<div>AbstractBackground:<p>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.</p>Methods:<p>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).</p>Results:<p>In the CCSS cohort, nine SNPs were found to be suggestive (<i>P</i> < 10^–7) or statistically significantly (<i>P</i> < 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.</p>Conclusions:<p>We were not able to replicate our findings of SNPs associated with pregnancy in childhood cancer survivors.</p>Impact:<p>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.</p></div>

Duke Scholars

Author Bo Hu Biostatistics & Bioinformatics, Division of Biostatistics