scholarly journals Interactions Between Genome-wide Significant Genetic Variants and Circulating Concentrations of Insulin-like Growth Factor 1, Sex Hormones, and Binding Proteins in Relation to Prostate Cancer Risk in the National Cancer Institute Breast and Prostate Cancer Cohort Consortium

2012 ◽  
Vol 175 (9) ◽  
pp. 926-935 ◽  
Author(s):  
Konstantinos K. Tsilidis ◽  
Ruth C. Travis ◽  
Paul N. Appleby ◽  
Naomi E. Allen ◽  
Sara Lindstrom ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Growth Factor ◽  
Cancer Risk ◽  
Sex Hormones ◽  
National Cancer Institute ◽  
Genetic Variants ◽  
Binding Proteins ◽  
Prostate Cancer Risk ◽  
Genome Wide ◽  
Breast And Prostate Cancer

scholarly journals Do sex hormones confound or mediate the effect of chronotype on breast and prostate cancer? A Mendelian randomization study.

2021 ◽  
Author(s):  
Bryony L Hayes ◽  
Timothy Robinson ◽  
Siddhartha P. Kar ◽  
Katherine S Ruth ◽  
Konstantinos K Tsilidis ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Prostate Cancer ◽  
Cancer Risk ◽  
Protective Effect ◽  
Sex Hormones ◽  
Prostate Cancer Risk ◽  
Total Testosterone ◽  
Testosterone Levels ◽  
Bioavailable Testosterone ◽  
Breast And Prostate Cancer

BACKGROUND Previous research has demonstrated that a morning-preference chronotype is protective against both breast and prostate cancer. Sex hormones have been implicated in relation to both chronotype and the development of both cancers. This study aims to assess whether sex hormones confound or mediate the effect of chronotype on breast and prostate cancer risk using a Mendelian Randomization (MR) framework. METHODS We obtained genetic variants strongly (p<5x10-8) associated with chronotype and sex hormones (total testosterone, bioavailable testosterone, sex hormone binding globulin (SHBG), and oestradiol from previously published genome-wide association studies (GWAS) that had been undertaken in UK Biobank and 23andMe (n=244,207 females and n=205,527 males). These variants were used to investigate causal relationships with risk of breast and prostate cancer using summary data from the largest available consortia in breast (nCases/nControls=133,384/ 113,789) and prostate cancer (nCases/nControls=79,148/61,106). This was achieved using a series of MR approaches: univariable, bidirectional and multivariable. Results Overall, we found evidence for a protective effect of genetically predicted tendency towards morning preference on both breast (OR=0.93, 95% CI:0.88, 1.00) and prostate (OR=0.90, 95% CI:0.83, 0.97) cancer risk. There was evidence that an increased tendency to morning preference reduces bioavailable testosterone levels in both females (mean SD difference=-0.08, 95% CI:-0.12, -0.05) and males (mean SD difference=-0.06, 95% CI:-0.09, -0.03), and reduces total testosterone levels in females (mean SD difference=-0.07, 95% CI:-0.10, -0.03). We also found evidence to support higher total and bioavailable testosterone increasing the risk of breast cancer (OR=1.15, 95% CI:1.07, 1.23, OR=1.10, 95% CI:1.01, 1.19 respectively) and higher bioavailable testosterone increasing prostate cancer risk (OR=1.22, 95% CI:1.08, 1.37). While findings from univariable and bidirectional MR analyses indicated that testosterone may lie on the causal pathway between chronotype and cancer risk, there was evidence for a bidirectional association between chronotype and testosterone in females, implicating testosterone as both a confounder and mediator of the chronotype effect on breast cancer risk. However, the effects of chronotype remained largely unchanged when accounting for testosterone in multivariable MR, suggesting that any confounding or mediating effect is likely to be minimal. Conclusions This study has extended previous findings regarding the protective effect of chronotype on breast cancer and found evidence to suggest that morning preference also reduces prostate cancer risk in men. While testosterone levels were found to be closely linked with both chronotype and cancer risk, there was inconsistent evidence for the role of testosterone in mediating the effect of morning preference chronotype on both breast and prostate cancer. Findings regarding the potential protective effect of chronotype on both breast and prostate cancer risk are clinically interesting. However, this may not serve as a direct target for intervention, since it is difficult to modify someone's morning/evening preference. Given this, further studies are needed to investigate the mechanisms underlying this effect and to identify other potential modifiable intermediates.

scholarly journals A genome-wide search for loci interacting with known prostate cancer risk-associated genetic variants

2012 ◽  
Vol 33 (3) ◽  
pp. 598-603 ◽  
Author(s):  
Sha Tao ◽  
Zhong Wang ◽  
Junjie Feng ◽  
Fang-Chi Hsu ◽  
Guangfu Jin ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Risk ◽  
Genetic Variants ◽  
Prostate Cancer Risk ◽  
Genome Wide ◽  
A Genome ◽  
Genome Wide Search
Sign in / Sign up

Export Citation Format

Share Document