Approved research

Investigating the associations between sex steroid hormone concentrations and risk of cancer development and survival

Lay summary

We propose to investigate the associations between genetic variants related to sex steroid hormone concentrations (e.g., testosterone and estradiol) and sex hormone binding globulin (SHBG), pre-diagnostic serum concentrations of the aforementioned hormones and risk of cancer development, death and survival, overall and by cancer site. We also propose to conduct a genome-wide association study (GWAS) and an exposure-wide association study (EWAS) for testosterone, estradiol and SHBG concentrations. The role of sex steroid hormones in cancer development and survival is unclear. Hormonal factors are important determinants of breast cancer risk, but several unanswered questions remain. Prostatic growth strongly depends on androgens, but epidemiological evidence has failed to show statistically significant associations for prostate cancer risk. Several other cancers appear to have different sex-specific incidence rates, and it has been hypothesized that sex hormones may alter their risk. If causal, associations between sex hormones and risk of cancer development and survival might be of great importance for public health, as estrogens and androgens decrease with increasing age. We propose to explore the associations between genetic variants related to sex steroid hormone concentrations identified in genome-wide association studies and risk of cancer development, death and survival, overall and by cancer site. In addition, we will investigate associations between pre-diagnostic serum testosterone, estradiol and SHBG concentrations and risk of cancer development and survival. We request to get genetic, risk factor, biomarker, and clinical data for the full cohort. Linkages to death and cancer registry data will be also requested to appropriately study risk of cancer development, death and survival.