Anslem J. M Hennis

Diabetes, hypertension, and central obesity as cataract risk factors in a black population. The Barbados Eye Study

OBJECTIVE The increased cataract prevalence of black populations, especially of cortical cataract, remains unexplained. The authors evaluate the relationships of diabetes, hypertension, and obesity patterns to lens opacities, by age, among 4314 black participants in the Barbados Eye Study. DESIGN AND PARTICIPANTS Prevalence study of a random sample of the Barbados population, ages 40 to 84 years (84% participation). MAIN OUTCOME MEASURES Associations with age-related lens changes (grade > or = 2 in the Lens Opacities Classification System II at the slit lamp) were evaluated in logistic regression analyses by age (persons < 60 years and > or = 60 years). Results are presented as odds ratios (OR) with 95% confidence intervals. RESULTS Of the 1800 participants with lens changes, most had cortical opacities. Diabetes history (18% prevalence) was related to all lens changes, especially at younger ages (age < 60 years: OR = 2.23 [1.63, 3.04]; age > or = 60 years: OR = 1.63 [1.22, 2.17]). Diabetes also increased the risk of cortical opacities (age < 60 years: OR = 2.30 [1.63, 3.24]; age > or = 60 years: OR = 1.42 [1.03, 1.96]); additional risk factors were high diastolic blood pressure (age < 60 years: OR = 1.49 [1.00, 2.23]) and higher waist/hip ratio (all ages: OR = 1.36 [1.00, 1.84]). Diabetes was also related to posterior subcapsular opacities. Glycated hemoglobin levels were positively associated with cortical and posterior subcapsular opacities. Overall, 14% of the prevalence of lens changes could be attributed to diabetes. CONCLUSIONS The high prevalence of cortical opacities was related to diabetes, hypertension, and abdominal obesity, which also are common in this and other black populations. Interventions to modify these risk factors, especially in populations in which they are highly prevalent, may have implications to control visual loss from cataract, which is the first cause of blindness worldwide.

Two susceptibility loci identified for prostate cancer aggressiveness

Most men diagnosed with prostate cancer will experience indolent disease; hence discovering genetic variants that distinguish aggressive from non-aggressive prostate cancer is of critical clinical importance for disease prevention and treatment. In a multistage, case-only genome-wide association study of 12,518 prostate cancer cases, we identify two loci associated with Gleason score, a pathological measure of disease aggressiveness: rs35148638 at 5q14.3 (RASA1, P=6.49×10-9) and rs78943174 at 3q26.31 (NAALADL2, P=4.18×10-8). In a stratified case-control analysis, the SNP at 5q14.3 appears specific for aggressive prostate cancer (P=8.85×10-5) with no association for non-aggressive prostate cancer compared to controls (P=0.57). The proximity of these loci to genes involved in vascular disease suggests potential biological mechanisms worthy of further investigation.

Prostate cancer susceptibility in men of African ancestry at 8q24

The 8q24 region harbors multiple risk variants for distinct cancers, including >8 for prostate cancer. In this study, we conducted fine mapping of the 8q24 risk region (127.8-128.8Mb) in search of novel associations with common and rare variation in 4853 prostate cancer case patients and 4678 control subjects of African ancestry. All statistical tests were two-sided. We identified three independent associations at P values of less than 5.00×10(-8), all of which were replicated in studies from Ghana and Uganda (combined sample = 5869 case patients, 5615 control subjects; rs114798100: risk allele frequency [RAF] = 0.04, per-allele odds ratio [OR] = 2.31, 95% confidence interval [CI] = 2.04 to 2.61, P = 2.38×10(-40); rs72725879: RAF = 0.33, OR = 1.37, 95% CI = 1.30 to 1.45, P = 3.04×10(-27); and rs111906932: RAF = 0.03, OR = 1.79, 95% CI = 1.53 to 2.08, P = 1.39×10(-13)). Risk variants rs114798100 and rs111906923 are only found in men of African ancestry, with rs111906923 representing a novel association signal. The three variants are located within or near a number of prostate cancer-associated long noncoding RNAs (lncRNAs), including PRNCR1, PCAT1, and PCAT2. These findings highlight ancestry-specific risk variation and implicate prostate-specific lncRNAs at the 8q24 prostate cancer susceptibility region.