Generalizability of established prostate cancer risk variants in men of African ancestry.

Genome-wide association studies have identified more than 80 risk variants for prostate cancer, mainly in European or Asian populations. The generalizability of these variants in other racial/ethnic populations needs to be understood before the loci can be used widely in risk modeling. In our study, we examined 82 previously reported risk variants in 4,853 prostate cancer cases and 4,678 controls of African ancestry. We performed association testing for each variant using logistic regression adjusted for age, study and global ancestry. Of the 82 known risk variants, 68 (83%) had effects that were directionally consistent in their association with prostate cancer risk and 30 (37%) were significantly associated with risk at p < 0.05, with the most statistically significant variants being rs116041037 (p = 3.7 × 10(-26) ) and rs6983561 (p = 1.1 × 10(-16) ) at 8q24, as well as rs7210100 (p = 5.4 × 10(-8) ) at 17q21. By exploring each locus in search of better markers, the number of variants that captured risk in men of African ancestry (p < 0.05) increased from 30 (37%) to 44 (54%). An aggregate score comprised of these 44 markers was strongly associated with prostate cancer risk [per-allele odds ratio (OR) = 1.12, p = 7.3 × 10(-98) ]. In summary, the consistent directions of effects for the vast majority of variants in men of African ancestry indicate common functional alleles that are shared across populations. Further exploration of these susceptibility loci is needed to identify the underlying biologically relevant variants to improve prostate cancer risk modeling in populations of African ancestry.

8q24 risk alleles and prostate cancer in African-Barbadian men.

BACKGROUND: African American men (AA) exhibit a disproportionate share of prostate cancer (PRCA) incidence, morbidity, and mortality. Several genetic association studies have implicated select 8q24 loci in PRCA risk in AA. The objective of this investigation is to evaluate the association between previously reported 8q24 risk alleles and PRCA in African-Barbadian (AB) men known to have high rates of PRCA. METHODS: Ten previously reported candidate tag SNPs were genotyped and/or imputed in the 8q24 region in 532 AB men with PRCA and 513 AB controls from the Prostate Cancer in a Black Population (PCBP) study. RESULTS: Rs2124036 was significant in AB men, (OR = 2.7, 95% CI (1.3-5.3), P = 0.005, Empirical (max (T), corrected for multiple testing) P = 0.03) for the homozygous C/C genotype. Only a single SNP from this region remained statistically significant in our analysis of our AB population. These results may indicate the presence of a founder effect or due to the chosen SNPs not tagging an ancestral haplotype bearing the 8q24 risk allele(s) in this population or could reflect inadequate power to detect an association. We conducted a meta-analysis including our AB population along with two additional African Caribbean populations from Tobago and Jamaica for SNPs rs16901979 and rs1447295. Meta-analysis results were most significant for rs16901979 A allele (Z score 2.73; P = 0.006) with a summary OR = 1.31 (95% CI: 1.09-1.58). CONCLUSIONS: Additional studies are needed to provide deeper genotype coverage to further interrogate the 8q24 region to understand its contribution to PRCA in this population.

Fine mapping of breast cancer genome-wide association studies loci in women of African ancestry identifies novel susceptibility markers.

Numerous single nucleotide polymorphisms (SNPs) associated with breast cancer susceptibility have been identified by genome-wide association studies (GWAS). However, these SNPs were primarily discovered and validated in women of European and Asian ancestry. Because linkage disequilibrium is ancestry-dependent and heterogeneous among racial/ethnic populations, we evaluated common genetic variants at 22 GWAS-identified breast cancer susceptibility loci in a pooled sample of 1502 breast cancer cases and 1378 controls of African ancestry. None of the 22 GWAS index SNPs could be validated, challenging the direct generalizability of breast cancer risk variants identified in Caucasians or Asians to other populations. Novel breast cancer risk variants for women of African ancestry were identified in regions including 5p12 (odds ratio [OR] = 1.40, 95% confidence interval [CI] = 1.11-1.76; P = 0.004), 5q11.2 (OR = 1.22, 95% CI = 1.09-1.36; P = 0.00053) and 10p15.1 (OR = 1.22, 95% CI = 1.08-1.38; P = 0.0015). We also found positive association signals in three regions (6q25.1, 10q26.13 and 16q12.1-q12.2) previously confirmed by fine mapping in women of African ancestry. In addition, polygenic model indicated that eight best markers in this study, compared with 22 GWAS-identified SNPs, could better predict breast cancer risk in women of African ancestry (per-allele OR = 1.21, 95% CI = 1.16-1.27; P = 9.7 × 10(-16)). Our results demonstrate that fine mapping is a powerful approach to better characterize the breast cancer risk alleles in diverse populations. Future studies and new GWAS in women of African ancestry hold promise to discover additional variants for breast cancer susceptibility with clinical implications throughout the African diaspora.

A genome-wide association study of breast cancer in women of African ancestry.

Genome-wide association studies (GWAS) in diverse populations are needed to reveal variants that are more common and/or limited to defined populations. We conducted a GWAS of breast cancer in women of African ancestry, with genotyping of >1,000,000 SNPs in 3,153 African American cases and 2,831 controls, and replication testing of the top 66 associations in an additional 3,607 breast cancer cases and 11,330 controls of African ancestry. Two of the 66 SNPs replicated (p < 0.05) in stage 2, which reached statistical significance levels of 10(-6) and 10(-5) in the stage 1 and 2 combined analysis (rs4322600 at chromosome 14q31: OR = 1.18, p = 4.3 × 10(-6); rs10510333 at chromosome 3p26: OR = 1.15, p = 1.5 × 10(-5)). These suggestive risk loci have not been identified in previous GWAS in other populations and will need to be examined in additional samples. Identification of novel risk variants for breast cancer in women of African ancestry will demand testing of a substantially larger set of markers from stage 1 in a larger replication sample.

Evaluation of 19 susceptibility loci of breast cancer in women of African ancestry.

Multiple breast cancer susceptibility loci have been identified in genome-wide association studies (GWAS) in populations of European and Asian ancestry using array chips optimized for populations of European ancestry. It is important to examine whether these loci are associated with breast cancer risk in women of African ancestry. We evaluated 25 single nucleotide polymorphisms (SNPs) at 19 loci in a pooled case-control study of breast cancer, which included 1509 cases and 1383 controls. Cases and controls were enrolled in Nigeria, Barbados and the USA; all women were of African ancestry. We found significant associations for three SNPs, which were in the same direction and of similar magnitude as those reported in previous fine-mapping studies in women of African ancestry. The allelic odds ratios were 1.24 [95% confidence interval (CI): 1.04-1.47; P = 0.018] for the rs2981578-G allele (10q26/FGFR2), 1.34 (95% CI: 1.10-1.63; P = 0.0035) for the rs9397435-G allele (6q25) and 1.12 (95% CI: 1.00-1.25; P = 0.04) for the rs3104793-C allele (16q12). Although a significant association was observed for an additional index SNP (rs3817198), it was in the opposite direction to prior GWAS studies. In conclusion, this study highlights the complexity of applying current GWAS findings across racial/ethnic groups, as none of GWAS-identified index SNPs could be replicated in women of African ancestry. Further fine-mapping studies in women of African ancestry will be needed to reveal additional and causal variants for breast cancer.

Recurrent BRCA1 and BRCA2 mutations in breast cancer patients of African ancestry.

Recurrent mutations constituted nearly three quarters of all BRCA1 mutations and almost half of all BRCA2 mutations identified in the first cohort of the Nigerian Breast Cancer Study. To further characterize breast/ovarian cancer risks associated with BRCA1/BRCA2 mutations in the African diaspora, we genotyped recurrent mutations among Nigerian, African American, and Barbadian breast cancer patients. A replication cohort of 356 Nigerian breast cancer patients was genotyped for 12 recurrent BRCA1/2 mutant alleles (Y101X, 1742insG, 4241delTG, M1775R, 4359insC, C64Y, 1623delTTAAA, Q1090X, and 943ins10 from BRCA1, and 1538delAAGA, 2630del11, and 9045delGAAA from BRCA2) by means of SNaPshot followed by direct sequencing or by direct sequencing alone. In addition, 260 African Americans and 118 Barbadians were genotyped for six of the recurrent BRCA1 mutations by SNaPshot assay. Of all the BRCA1/2 recurrent mutations we identified in the first cohort, six were identified in 11 patients in the replication study. These mutation carriers constitute 3.1 % [95 % Confidence Interval (CI) 1.6-5.5 %] of the replication cohort. By comparison, 6.9 % (95 % CI 4.7-9.7 %) of the discovery cohort carried BRCA1/2 recurrent mutations. For the subset of recurrent mutations we tested in breast cancer cases from Barbados or the United States, only two 943ins10 carriers were identified in African Americans. Nigerian breast cancer patients from Ibadan carry a broad and unique spectrum of BRCA1/2 mutations. Our data suggest that BRCA1/2 mutation testing limited to recurrent mutations is not sufficient to understand the BRCA1/2-associated breast cancer risk in African populations in the diaspora. As the cost of Sanger sequencing is considerably reduced, deploying innovative technologies such as high throughput DNA sequencing of BRCA1/2 and other cancer susceptibility genes will be essential for identifying high-risk individuals and families to reduce the burden of aggressive early onset breast cancer in low-resource settings.

Lack of association between common single nucleotide polymorphisms in the TERT-CLPTM1L locus and breast cancer in women of African ancestry.

As one of the most common cancers worldwide, breast cancer places an extraordinary burden on the populations of African ancestry. Common SNPs in the TERT-CLPTM1L locus have been reported to be associated with several types of cancer, including breast cancer. We sought to investigate whether the previously reported common single nucleotide polymorphisms (SNPs) in the TERT-CLPTM1L locus could also contribute to the breast cancer risk in women of African ancestry. We genotyped eleven SNPs in 2,892 women of African descent but were unable to detect any significant association between TERT-CLPTM1L SNPs and their predispositions for breast cancer risk. Given the differences in linkage disequilibrium patterns across populations, our findings suggest that larger independent studies from diverse populations are expected to evaluate the importance of the TERT-CLPTM1L locus in breast cancer.

A signature of balancing selection in the region upstream to the human UGT2B4 gene and implications for breast cancer risk.

UDP-glucuronosyltransferase 2 family, polypeptide B4 (UGT2B4) is an important metabolizing enzyme involved in the clearance of many xenobiotics and endogenous substrates, especially steroid hormones and bile acids. The HapMap data show that numerous SNPs upstream of UGT2B4 are in near-perfect linkage disequilibrium with each other and occur at intermediate frequency, indicating that this region might contain a target of natural selection. To investigate this possibility, we chose three regions (4.8 kb in total) for resequencing and observed a striking excess of intermediate-frequency alleles that define two major haplotypes separated by many mutation events and with little differentiation across populations, thus suggesting that the variation pattern upstream UGT2B4 is highly unusual and may be the result of balancing selection. We propose that this pattern is due to the maintenance of a regulatory polymorphism involved in the fine tuning of UGT2B4 expression so that heterozygous genotypes result in optimal enzyme levels. Considering the important role of steroid hormones in breast cancer susceptibility, we hypothesized that variation in this region could predispose to breast cancer. To test this hypothesis, we genotyped tag SNP rs13129471 in 1,261 patients and 825 normal women of African ancestry from three populations. The frequency comparison indicated that rs13129471 was significantly associated with breast cancer after adjusting for ethnicity [P = 0.003; heterozygous odds ratio (OR) 1.02, 95% confidence interval (CI) 0.81-1.28; homozygous OR 1.50, 95% CI 1.15-1.95]. Our results provide new insights into UGT2B4 sequence variation and indicate that a signal of natural selection may lead to the identification of disease susceptibility variants.

Validation of a quantitative FFQ for the Barbados National Cancer Study.

OBJECTIVE: To assess the validity of a 148-item quantitative FFQ (QFFQ) that was developed for the Barbados National Cancer Study (BNCS) to determine dietary intake over 12 months and examine the dietary risk factors. DESIGN: A cross-sectional validation study of the QFFQ against 4 d food diaries. Spearman's rank correlations (ρ), intra-class correlation coefficients (ICC) and weighted κ were computed as measures of concordance, adjusting for daily variations in the food diaries. Cross-classification tables and Bland-Altman plots were created for further assessment. SETTING: BNCS is a case-control study of environmental risk factors for breast and prostate cancer in a predominantly African-origin population in Barbados. SUBJECTS: Fifty-four individuals (21 years and older) were recruited among controls in the BNCS who were frequency-matched on sex and age group to breast and prostate cancer cases. RESULTS: Similar mean daily energy intake was derived from the food diary (8201 kJ (1960 kcal)) and QFFQ (7774 kJ (1858 kcal)). Rho for energy and macronutrients ranged from 0·66 (energy) to 0·17 (dietary fibre). The percentage of energy from carbohydrates and protein showed the highest and lowest ICC among macronutrients (0·63 and 0·27, respectively). The highest weighted κ was observed for energy (0·45). When the nutrient intake was divided into quartiles, approximately 34 % of the observations were in the same quartile. CONCLUSIONS: This investigation supports the validity of the QFFQ as a method for assessing long-term dietary intake except for dietary fibre, folate, vitamins A, E and B12. The instrument will be a useful tool in the analysis of diet-cancer associations in the BNCS.

Causes of visual loss and their risk factors: an incidence summary from the Barbados Eye Studies.

OBJECTIVES: To summarize incidence and risk factors for each main cause of visual loss in an African-Caribbean population and discuss the implications of these data from a public health perspective. METHODS: A nationally representative cohort (n = 4 709; ages 40-84 years at baseline) had ophthalmic and other examinations over 9 years. Incidence rates were estimated by the product-limit approach. Risk factors were evaluated from Cox regression models. RESULTS: Average incidence was ~ 0.1% per year for blindness (< 6/120) and 0.7% per year for low vision (< 6/18 to 6/120), increasing steeply with age (P < 0.05) and affecting related quality of life (P < 0.05). Age-related cataract and open-angle glaucoma (OAG) accounted for 73.2% of blindness and diabetic retinopathy (DR) for 8.9%; cataract caused two-thirds of low vision. Average incidence was 5.1% per year for all lens changes (gradable/ungradable opacities or aphakia) and 0.4% per year for cataract surgery. Incidence of definite OAG was 0.5% per year (0.9% for suspect or probable); 53% of the affected were unaware. Persons with diabetes mellitus (DM) had a DR incidence of 4.4% per year. Age-related macular degeneration was rare (0.08% per year). Main cataract risk factors were age and DM. OAG incidence increased with age, intraocular pressure, family history, low ocular perfusion pressures, and thinner corneas. DR risk increased with early DM onset, DM duration, oral/insulin treatment, increased systolic and diastolic blood pressures, and hyperglycemia. Antihypertensive treatment halved DR risk. CONCLUSIONS: Incidence of visual impairment was high and significantly affected quality of life. Age-related cataract and OAG caused ~ 75% of blindness, indicating the need for public health action to increase appropriate cataract surgery and early OAG detection and treatment. Controlling DM and hypertension would help prevent DR-related complications and could lower cataract risk, further decreasing visual loss.

Using the internet to educate adolescents about osteoporosis: application of a tailored web-education system.

Osteoporosis is a "pediatric disease with geriatric consequences." This article describes the development and pilot testing of an online system to educate high school students grades 9-12 about osteoporosis; an age where positive health changes could have long lasting effects. The intervention goal was to improve knowledge about osteoporosis and intent to adopt healthy bone practices. Online pre- and postintervention surveys evaluated participants' pre- and postintervention osteoporosis knowledge, attitudes, preventive practices, and postintervention intent to change healthy bone practices. Participants completed the Web-based program that provided detailed information about osteoporosis, and healthy bone practices, immediately after completing the pretest and just prior to completing the posttest. Eighty-nine students completed both the pre/posttests and were included in data analysis. Participants ranged in age from 13 to 17 and 75% were Caucasian (n = 65). Based on pre/posttest scores of 9 factual questions, students significantly improved their knowledge (p < .0001) and overall knowledge rating about osteoporosis at posttest (p < .001). Participants changed their perception regarding the disease's seriousness (p < .001), and considered adopting osteoporosis prevention practices. The study shows that an interactive educational Web site is an effective method for increasing awareness and understanding of osteoporosis in high school students.

Risk factors for breast cancer in a black population--the Barbados National Cancer Study.

The Barbados National Cancer Study (BNCS) is a nationwide case-control study investigating environmental and genetic factors for breast cancer (BC) in a predominantly African-origin population with similar ancestry as African-Americans. This report evaluates associations of incident BC in the BNCS to various factors, including demographic, anthropometric, reproductive and family history variables, not investigated previously in this population. The BNCS included 241 incident BC cases and 481 age-matched female controls, with mean ages of 57 and 56 years, respectively. In addition to a reported family history of BC in a close relative [odds ratios (OR) = 3.74, 95% CI (1.41, 9.90) in a parent; OR = 3.26 (1.47, 7.21) in a sibling], other factors associated with BC were older age at first full-term pregnancy [OR = 1.04 (1.00, 1.07)] and having a history of benign breast disease [OR = 1.88 (1.19, 2.99)]. Increased parity reduced the risk of BC [OR = 0.34 (0.15, 0.77) among those with >or=3 children]. The reproductive patterns of African-Barbadian (AB) women tended to differ from those of African-American (AA) women (later age of menarche, earlier age at first pregnancy, higher frequency of lactation and infrequent use of exogenous hormones) and could help to explain their considerably lower postmenopausal incidence of BC. The relationship between reported family history and BC, combined with the associations noted for several reproductive and other variables, supports the genetic and environmental contributions to BC, which may vary in populations across the African diaspora. Further investigations of other populations may clarify these issues.

Breast cancer incidence and mortality in a Caribbean population: comparisons with African-Americans.

We describe breast cancer incidence and mortality in the predominantly African-origin population of Barbados, which shares an ancestral origin with African-Americans. Age-standardized incidence rates were calculated from histologically confirmed breast cancer cases identified during a 45-month period (July 2002-March 2006). Mortality rates were estimated from death registrations over 10-years starting January 1995. There were 396 incident cases of breast cancer for an incidence rate of 78.1 (95% confidence interval (CI) 70.5-86.3), standardized to the US population. Breast cancer incidence in African-Americans between 2000 and 2004 was 143.7 (142.0-145.5) per 100,000. Incidence peaked at 226.6 (174.5-289.4) per 100,000 among Barbadian women aged 50-54 years, and declined thereafter, a pattern in marked contrast to trends in African-American women, whose rates continued to increase to a peak of 483.5 per 100,000 in those aged 75-79 years. Incidence rate ratios comparing Barbadian and African-American women showed no statistically significant differences among women aged>or=55 years (p

Body size and breast cancer in a black population--the Barbados National Cancer Study.

OBJECTIVE: To evaluate the relationship between body size and incident breast cancer in an African-origin Caribbean population. METHODS: This investigation is based on 222 incident breast cancer cases and 454 controls from the Barbados National Cancer Study (BNCS) in whom body size variables that included height, weight, body-mass index (BMI), waist and hip circumferences (WC, HC), and waist-hip ratio (WHR) were compared. Multivariate-adjusted logistic regression analyses were performed and the findings are presented as odds ratios (ORs) with 95% confidence intervals (CI). RESULTS: Although 33% of cases and 39% of controls were obese (BMI > or = 30 kg/m(2)), BMI was not found to be a significant predictor of breast cancer in the multivariate analyses. Tall stature increased risk among women > or =50 years (OR = 2.16, 95% CI (1.02, 4.58)), and a dual effect with age was suggested for both WC and WHR (decreased risk for those aged < or =50 years; increased risk among those > or =50 years). CONCLUSIONS: Body size appears to influence the risk of breast cancer in this population of African origin. The BNCS data suggest that a few, but not all body size factors play a role in breast cancer risk, and that age may affect these relationships.

Nine-year incidence of visual impairment in the Barbados Eye Studies.

OBJECTIVE: To describe the 9-year incidence of visual impairment and primary causes of blindness among black participants of the Barbados Eye Studies (BES). DESIGN: Population-based prospective cohort study. PARTICIPANTS: The BES followed a nationally representative cohort selected by simple random sampling, aged 40 to 84 years at baseline, with reexaminations after 4 years (Barbados Incidence Study of Eye Diseases [BISED]) and 9 years (BISED II). BISED II included 2793 (81%) of those eligible. METHODS: Cumulative 9-year incidence rates were estimated by the Product-Limit approach. The study was reviewed and approved by the institutional review boards of collaborating institutions. MAIN OUTCOME MEASURES: Best-corrected visual acuity (VA) was assessed by the Ferris-Bailey chart, following a modified Early Treatment of Diabetic Retinopathy Study protocol. Low vision and blindness were defined by World Health Organization (WHO) criteria as VA <6/18 to 6/120, and <6/120, respectively, in the better eye, and by U.S. criteria as VA < or =20/40 and < or =20/200, respectively. Vision loss was defined as a decrease of 15 letters or more read correctly in the better eye between baseline and follow-up examinations. RESULTS: The 9-year incidence was 1.0% and 2.1% for blindness and 6.0% and 9.0% for low vision, by WHO and U.S. criteria, respectively. Older age at baseline was associated with higher incidence of low vision and blindness, reaching 23.0% (95% confidence interval [CI], 18.8-28.0) and 4.3% (95% CI, 2.7-6.9) at age 70 years or more, based on WHO criteria. The primary causes of incident bilateral blindness (U.S. criteria) in 126 eyes were age-related cataract (48.3%), open-angle glaucoma (OAG) (14.3%), combined cataract and OAG (6.3%), diabetic retinopathy (8.7%), and optic atrophy (7.1%). Age-related macular degeneration (2.4%) rarely caused blindness. CONCLUSIONS: Incident visual impairment is exceedingly high in this population. Cataract, OAG, and diabetic retinopathy remain the major causes of blindness, underpinning the clinical and public health significance of these conditions in this and similar populations.

Impact of glaucoma, lens opacities, and cataract surgery on visual functioning and related quality of life: the Barbados Eye Studies.

PURPOSE: To determine the relationship of open-angle glaucoma (OAG) and lens opacities to visual functioning and related quality of life (QOL), by using the 25-item National Eye Institute Visual Function Questionnaire (NEI-VFQ-25) in a population of African origin. METHODS: The study included 962 black participants of the Barbados Eye Studies with known glaucoma, prior cataract surgery, visual acuity (VA)

Nine-year incidence and risk factors for pterygium in the barbados eye studies.

PURPOSE: To present 9-year incidence data and associated risk factors for pterygium among black participants in the Barbados Eye Studies. DESIGN: Population-based incidence study. PARTICIPANTS: A total of 1888 black participants, aged 40 to 84 years, who were free of pterygium at baseline and received an ophthalmologic study examination at the 9-year follow-up. METHODS: Age and sex-specific 9-year incidence of pterygium is presented. Risk factors were initially identified using Mantel-Haenszel analyses, and significant factors (P<0.10) were subsequently included in multivariate logistic regression models. Odds ratios (OR) and 95% confidence intervals (CI) are provided. MAIN OUTCOME MEASURES: Development of pterygium, defined as the presence of a raised fleshy growth that crosses the limbus and encroaches onto the clear cornea. RESULTS: The 9-year incidence of pterygium was 11.6% (95% CI, 10.1-13.1), with no clear pattern with increasing age and no statistically significant differences between genders. Multivariate logistic regression analyses indicated that having a lifetime outdoor job location was positively associated with the development of pterygium (OR = 1.51; 95% CI, 1.05-2.16), whereas darker skin color (OR = 0.67; 95% CI, 0.46-0.97) and use of any prescription lenses (OR = 0.58; 95% CI, 0.42-0.81) were found to be protective factors. CONCLUSIONS: The incidence of pterygium was high in this population, for an average of 1.3% per year. Working outdoors increased the risk 1.5-fold, whereas having a darker skin complexion and using eyewear for either reading or distance substantially decreased the risk of developing pterygium. These data suggest that absorption of ultraviolet light plays a role in this condition and that preventive strategies are needed to decrease the burden of pterygium development in this and other populations. FINANCIAL DISCLOSURE(S): The authors have no proprietary or commercial interest in any materials discussed in this article.

Risk factors for incident open-angle glaucoma: the Barbados Eye Studies.

PURPOSE: To evaluate risk factors for definite open-angle glaucoma (OAG), based on African-descent participants of the Barbados Eye Studies. DESIGN: Cohort study with 81% to 85% participation over 9 years' follow-up. PARTICIPANTS: We evaluated 3222 persons at risk, 40 to 84 years old, who did not have definite OAG at baseline. METHODS: Participants had standardized study visits at baseline and after 4 and 9 years, with structured interviews, blood pressure (BP), and other measurements. The ophthalmic protocol included automated perimetry, applanation tonometry, fundus photography, and comprehensive ophthalmologic examinations for those referred. Central corneal thickness (CCT) was measured in a subset at the 9-year examination. Incidence was estimated by the product-limit approach; relative risk ratios (RRs) with 95% confidence intervals (CIs) were based on Cox regression models with discrete time. MAIN OUTCOME MEASURE: Nine-year incidence of definite OAG. RESULTS: Over 9 years, 125 persons developed definite OAG (incidence, 4.4%; 95% CI, 3.7-5.2). Baseline factors influencing risk were age (RR, 1.04; 95% CI, 1.02-1.05 per year); family history of glaucoma (RR, 2.4; 95% CI, 1.3-4.6); higher intraocular pressure (IOP) (RR, 1.12; 95% CI, 1.08-1.16 per mmHg); lower systolic BP (RR, 0.91; 95% CI, 0.84-1.00 per 10 mmHg); and lower ocular systolic, diastolic, and mean perfusion pressures (RR, 0.66; 95% CI, 0.54-0.80 per 10 mmHg higher mean perfusion pressure) (RR, 2.6; 95% CI, 1.4-4.6 for low mean perfusion pressure [<40 mmHg]). Thinner CCT was also associated with OAG incidence (odds ratio, 1.41; 95% CI, 1.01-1.96 per 40 mum lower). CONCLUSIONS: This is the first report of risk factors for long-term OAG incidence; it is also based on a sizable number of new cases. Incidence was high in this African-descent population, where the established factors of older age, higher IOP, and family history contributed to risk. Additional predictors were vascular factors, including lower systolic BP, and particularly lower ocular perfusion pressures, which more than doubled risk. Thinner CCT was also a factor. These findings indicate a multifactorial etiology of OAG and suggest that similar risk factors apply across populations. Results are relevant for understanding OAG causation and identifying groups at high risk.

Open-angle glaucoma and mortality: The Barbados Eye Studies.

OBJECTIVE: To evaluate the relationship between open-angle glaucoma (OAG) and mortality in a black population at 9-years' follow-up. DESIGN: Population-based cohort study of 4092 black participants (aged 40-84 years at baseline) in the Barbados Eye Studies. Open-angle glaucoma was defined by visual field defects and optic disc damage, based on standardized examinations and photograph gradings. Ocular hypertension was defined by an intraocular pressure greater than 21 mm Hg or treatment, without OAG damage. Mortality was ascertained from death certificates. Cox proportional hazards regression analyses determined associations with mortality. RESULTS: After 9 years, 764 (19%) participants were deceased. Mortality was unrelated to overall OAG at baseline (n = 300) after adjustment for confounders. However, cardiovascular mortality tended to increase in persons with previously diagnosed/treated OAG (n = 141; relative risk [RR], 1.38, P = .07) and was significantly higher with treatment involving timolol maleate (RR, 1.91, P = .04). Cardiovascular deaths also tended to increase in persons with ocular hypertension at baseline (n = 498; RR, 1.28, P = .06). CONCLUSIONS: In this black population, cardiovascular mortality tended to increase in persons with previously diagnosed/treated OAG and ocular hypertension. The excess mortality associated with timolol maleate treatment of OAG, also found in a white population, warrants further investigation.