Abstract: PD13-06
Sources of Funding: This work was supported by the National Institutes of Health - National Institute of Aging [Grant numbers 1R21AG036938-01, 2R01 AG022095 and 1K12HD085852-01].

Introduction

Male infertility is an indicator of somatic health and has been linked to increased risk of cancer. Previous studies have shown increased thyroid cancer and melanoma risk in first (FDR) and second-degree relatives (SDR) of infertile men. In this study, investigate sex differences in cancer risk amongst FDRs and SDRs of men who underwent semen analysis (SA) as part of an infertility work-up relative to fertile population controls, in order to better understand the broader health implications of male infertility.

Methods

12,889 men with SA and complete FDR data and 8,032 men with SA and complete SDR data were matched by age and birth year to an equal number of fertile population controls with complete familial data from the Utah Population Database (UPDB). We performed a retrospective cohort analysis of thyroid cancer and melanoma risk by gender for FDRs (n = 130,689) and SDRs (n = 247,204) of these men using the Utah Cancer Registry (UCR). Cox proportional hazard regression models were used to test the association between semen quality and adult onset cancer. Models were stratified by sex and run separately for the following semen parameters: sperm count, sperm concentration, sperm motility, total motile count, sperm head morphology, and vitality.

Results

The FDRs and SDRs of azoospermic men had significantly increased overall risk of thyroid cancer relative to fertile controls (HR 2.12, 95% CI 1.26 - 3.57). By sex, female FDRs of azoospermic men had increased risk of thyroid cancer compared with male FDRs (HR 2.31, 95% CI 1.33 - 3.99 and HR 1.54, 95% CI 0.48 - 4.97, respectively), while no significant difference was seen amongst male and female SDRs (HR 1.57, 95% CI 1.03 - 2.39, and HR 1.54, 95% CI .95 - 2.52). There were no significant differences in thyroid cancer risk amongst male and female SDRs based on any of the semen parameters. No overall or sex specific difference in the risk of melanoma for FDRs or SDRs of men who underwent SA compared with relatives of fertile control subjects was observed.

Conclusions

Our results suggest that male infertility may be associated with increased overall and sex-specific risk thyroid cancer in relatives. Further study is needed to understand potential environmental exposures or shared biologic mechanisms of infertility and cancer that may account for these observations.

Funding

This work was supported by the National Institutes of Health - National Institute of Aging [Grant numbers 1R21AG036938-01, 2R01 AG022095 and 1K12HD085852-01].