Association between genetically proxied PCSK9 inhibition and prostate cancer risk: A Mendelian randomisation study.
Fang Si et al. PLoS medicine 2023 1 (1) e1003988
Using genetic variants associated with LDL cholesterol, liver-derived gene expression, and plasma protein levels, the researchers applied drug target Mendelian randomization (MR) and colocalization to examine the association between lipid-lowering drug targets and the risk of overall, early-onset, and advanced prostate cancer. Additional MR analyses were conducted to explore putative mediators of drug effects. This study provided evidence of an association between genetically proxied PCSK9 inhibition and lower risk of overall and early-onset prostate cancer supported by both MR and colocalization approaches.
Genetic determinants for the racial disparities in the risk of prostate and testicular cancers
I Uzamere et al, Comm Med, November 2, 2022
It has been observed that men of African ancestry have a higher incidence of prostate cancer and lower incidence of testicular cancer compared to men of European ancestry. However, little is known about underlying mechanisms accounting for these observations. The current study compares frequencies of all genetic alterations associated with risks of prostate cancer or testicular cancer between the two racial groups. Our findings suggest that differences in the frequencies of genetic alterations between the groups may help to explain the racial disparities in the risk of prostate and testicular cancers.
Polygenic risk of any, metastatic, and fatal prostate cancer in the Million Veteran Program.
Pagadala Meghana S et al. Journal of the National Cancer Institute 2022 10
90,750 male participants were included. Median age at last follow-up was 69 years. PHS290 was associated with fatal prostate cancer in the full cohort and for each racial and ethnic group (p<0.001). Comparing men in the highest 20% of PHS290 to those in the lowest 20% (based on percentiles from an independent training cohort), the hazard ratio for fatal prostate cancer was 4.42 [95%CI: 3.91-5.02]. When accounting for guideline-recommended risk factors (family history, race and ethnicity), PHS290 remained a strong independent predictor of any, metastatic, and fatal prostate cancer.
Two Factors to ID Men at Highest Risk for Prostate Cancer Death
R Nelson, Medscape, September 2022
A family history of prostate cancer has long been one of the few universally accepted risk factors for the disease. New findings now provide evidence that risk stratification based on family history and inherited polygenic risk can identify men at highest risk of dying from the disease before age 75. Men in the upper quartile of polygenic risk score or who had a family history of prostate or breast cancer accounted for close to 100% of prostate cancer deaths by age 75. This strategy can also identify men at low risk for prostate cancer, potentially sparing them from intensive prostate cancer screening.