A Germline Variant at 8q24 Contributes to Familial Clustering of Prostate Cancer in Men of African Ancestry

Although men of African ancestry have a high risk of prostate cancer (PCa), no genes or mutations have been identified that contribute to familial clustering of PCa in this population. We investigated whether the African ancestry–specific PCa risk variant at 8q24, rs72725854, is enriched in men with a PCa family history in 9052 cases, 143 cases from high-risk families, and 8595 controls of African ancestry. We found the risk allele to be significantly associated with earlier age at diagnosis, more aggressive disease, and enriched in men with a PCa family history (32% of high-risk familial cases carried the variant vs 23% of cases without a family history and 12% of controls). For cases with two or more first-degree relatives with PCa who had at least one family member diagnosed at age <60 yr, the odds ratios for TA heterozygotes and TT homozygotes were 3.92 (95% confidence interval [CI] = 2.13–7.22) and 33.41 (95% CI = 10.86–102.84), respectively. Among men with a PCa family history, the absolute risk by age 60 yr reached 21% (95% CI = 17–25%) for TA heterozygotes and 38% (95% CI = 13–65%) for TT homozygotes. We estimate that in men of African ancestry, rs72725854 accounts for 32% of the total familial risk explained by all known PCa risk variants. Patient summary: We found that rs72725854, an African ancestry–specific risk variant, is more common in men with a family history of prostate cancer and in those diagnosed with prostate cancer at younger ages. Men of African ancestry may benefit from the knowledge of their carrier status for this genetic risk variant to guide decisions about prostate cancer screening. © 2020 The AuthorsThe African ancestry–specific prostate cancer risk variant at 8q24, rs72725854, is enriched in men diagnosed at younger ages and men with a prostate cancer family history. Carriers of this risk allele would benefit from regular and earlier prostate cancer screening

Lipoprotein-associated phospholipase A₂ inflammatory biomarkers, and risk of cardiovascular disease in the Prospective Study of Pravastatin in the Elderly at Risk (PROSPER)

&lt;p&gt;&lt;b&gt;Objective&lt;/b&gt; &lt;br&gt;Lipoprotein-associated phospholipase A2 (Lp-PLA2) is an inflammatory biomarker that circulates mainly bound to LDL. We evaluated the association of Lp-PLA2 with vascular events in the elderly where the importance of LDL is diminished as a risk factor for coronary disease.&lt;/br&gt;&lt;/p&gt; &lt;p&gt;&lt;b&gt;Methods&lt;/b&gt; &lt;br&gt;Mass and activity of Lp-PLA2 were related to risk over 3.2 years for vascular events (definite or suspected death from CHD, non-fatal MI, fatal or non-fatal stroke) in the 2804 men and 3000 women age 70–82 years in the Prospective Study of Pravastatin in the Elderly (PROSPER).&lt;/br&gt;&lt;/p&gt; &lt;p&gt;&lt;b&gt;Results&lt;/b&gt; &lt;br&gt;Lp-PLA2 showed a moderate, positive association with risk of a vascular event with hazard ratios of 1.25 (confidence interval (CI) 1.02–1.54) for mass and 1.39 (CI 1.14–1.70) for activity for top versus bottom quartile. Risk associations were attenuated when classical risk factors, lipids and inflammatory markers – C-reactive protein and white cell count – were included in the models. Lp-PLA&lt;sub&gt;2&lt;/sub&gt; was unrelated to stroke risk. Inclusion of all three inflammatory markers in multivariate models negated the association of HDL cholesterol with risk (hazard ratio 0.98; CI 0.88–1.10) and increased prediction of coronary events; the C statistic rose from 63.2% to 64.4% (P &#x3C; 0.001).&lt;/br&gt;&lt;/p&gt; &lt;p&gt;&lt;b&gt;Conclusion&lt;/b&gt; &lt;br&gt;In elderly people Lp-PLA&lt;sub&gt;2&lt;/sub&gt;, alongside other inflammatory indices, is a potential biomarker for vascular events, particularly CHD.&lt;/br&gt;&lt;/p&gt