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In addition to clinical criteria, self-perceptions of vision-related functioning and well-being are recognized as important measures for characterizing the disability associated with visual impairment. This report assessed the impact of visual impairment in a subset of the African-origin participants of the population-based Barbados Eye Studies, using the US National Eye Institute's 25-item Visual Functioning Questionnaire (NEI-VFQ-25). Visual impairment was associated with significantly (P 0.01) lower VFQ scores in multidimensional aspects of vision-related quality of life (QOL), including vision-related activities and psychosocial functioning. Adjusted mean composite scores were 12 points (95% confidence interval: 9.5, 14.5) and 31 points (26.7, 34.6) lower for low vision and blindness, respectively, compared with no impairment, and 13 points (7.7, 17.6) lower for visual impairment not correctable, compared with correctable with refraction. In this population with high rates of visual disability, impaired visual acuity adversely impacted the self-perceived QOL, as measured by this instrument. Copyright © 2009 SAGE Publications Ltd. [ABSTRACT FROM AUTHOR]

BACKGROUND: The dietary habits of the Caribbean have been changing to include more fast foods and a less nutrient dense diet. The aims of this study are to examine dietary patterns in Barbados and highlight foods for a nutritional intervention. METHODS: Four-day food diaries collected from control participants in the population-based, case-control Barbados National Cancer Study (BNCS). RESULTS: Forty-nine adult participants (91% response) completed the diaries providing 191 days of dietary data. Total energy intake was almost identical to data collected 5-years earlier in the Barbados Food Consumption and Anthropometric Survey 2000, but the percent energy derived from fat was from 2.1% to 5.2% higher. Sugar intake exceeded the Caribbean recommendation almost four-fold, while intakes of calcium, iron (women only), zinc and dietary fibre were below recommendations. Fish and chicken dishes were the two largest sources of energy and fat. Sweetened drinks and juices provided over 40% of total sugar intake. CONCLUSIONS: These data provide existing dietary patterns and strongly justify a nutritional intervention program to reduce dietary risk factors for chronic disease. The intervention could focus on the specific foods highlighted, both regarding frequency and amount of consumption. Effectiveness can be evaluated pre- and post-intervention using our Food Frequency Questionnaire developed for BNCS. [ABSTRACT FROM AUTHOR]

Objective: To develop a quantitative food-frequency questionnaire (QFFQ) for the Barbados National Cancer Study (BNCS) that will permit examination of associations of diet with breast and prostate cancer.Design: Population intake data from the year 2000 Barbados Food Consumption and Anthropometric Surveys (BFCAS 2000) were used to derive a list of foods consumed by the population. A 192-item draft QFFQ was developed from this list.Setting: Barbados, West Indies provides an ideal environment to understand cancer risk in African-origin populations, with high relevance to African-Americans. The BNCS is a population-based case-control study examining risk factors for breast and prostate cancer in such populations.Subjects: A total of 1600 persons, 18 years and older, completed a 24-hour recall in the BFCAS 2000. Fifty of 63 randomly selected residents (79% response rate) gave additional updated information on foods consumed.Results: The 50 participants provided a one-time 24-hour recall and completed the draft QFFQ. The final instrument contains 148 items: breads, cakes, cereals = 17; rice, pastas, noodles = 8; dairy = 10; meat, fish, poultry = 42; fruit = 16; vegetables = 26; soft drinks = 14; alcoholic beverages = 5; others = 10. Additional questions include supplement use and food preparation methods such as grilling.Conclusion: The final instrument is concise, complete and the most up-to-date for assessing the food and nutrient intake of African-origin Barbadians and the associations with breast and prostate cancer. [ABSTRACT FROM AUTHOR]

Background: This study evaluated the association of age-related lens opacities with the use of nutritional supplements and demographic factors among 4314 black participants (> or = 40 years) in the population-based Barbados Eye Study.Methods: Lenses were classified at the slit lamp by the Lens Opacities Classification System II (LOCS II); a score > or = 2 was used to define the presence of gradable lens opacities, by type. Lens changes also included prior cataract surgery or cataract too advanced to grade. Associations with risk factors were evaluated by logistic regression analyses.Results: The study identified 1800 individuals with lens changes in at least one eye; 229 had nuclear opacities only; 851 had cortical opacities only. Older age and indicators of lower socioeconomic status (low education and/or non-professional occupation), were positively associated with both nuclear (odds ratio [OR] = 1.90) and cortical (OR = 1.47) opacities. Women had an increased risk of cortical opacities (OR = 1.41). Regular users of nutritional supplements were less likely to have lens changes (OR = 0.78) and, specifically, cortical opacities (OR = 0.77). The association with nutritional supplements was present in those < 70 years, but not at older ages.Conclusions: The study supports the association of lower socioeconomic status with lens changes, including nuclear and cortical lens opacities. The findings also suggest that regular users of nutritional supplements have a one-fourth lower risk of lens changes and particularly, of cortical opacities; a result seen at ages under 70 years. The associations with potentially modifiable factors indicate the need for further evaluations, given the high prevalence of lens opacities. [ABSTRACT FROM AUTHOR]

Background: Alcohol use is associated with breast cancer in many epidemiological studies. Most, however, have measured risk from recent consumption patterns, and only a few include analyses for duration of drinking or age that a woman started to drink. The authors studied the effect of these variables, as well as of recent alcohol consumption patterns, on breast cancer risk.Methods: Data from a large case-control study conducted in Long Island, New York from 1 January 1984 to 31 December 1986 were used. A total of 1214 women aged 20-79 years with incident breast cancer were interviewed. A control was selected for each case from driver's license files, and matched on age and county of residence. Alcohol consumption was measured as: ever versus never, grams of alcohol per day, age started drinking, and total years drinking.Results: After adjustment for breast cancer risk factors, the odds ratio for ever versus never drinking was 1.40 (95% confidence interval [CI] 1.09-1.79); odds ratios for > 0-5 and > or = 5 grams of alcohol use per day, as compared to nondrinkers, were 1.29 (95% CI: 1.00-1.65) and 1.46 (95% CI: 1.13-1.89), respectively. Age when drinking began was not related to breast cancer risk, but the greater the total years of drinking, up to 40 years (odds ratio 1.48, 95% CI: 1.13-1.93), the greater the risk. However, when grams per day and duration of drinking were simultaneously included in the multivariate model, duration was not important as a risk factor. This suggests that intensity of drinking may be the important factor for breast cancer risk. After covariate adjustment, risk from alcohol intake did not differ between pre- and postmenopausal women. [ABSTRACT FROM AUTHOR]

Multiple breast cancer loci have been identified in previous genome-wide association studies, but they were mainly conducted in populations of European ancestry. Women of African ancestry are more likely to have young-onset and oestrogen receptor (ER) negative breast cancer for reasons that are unknown and understudied. To identify genetic risk factors for breast cancer in women of African descent, we conducted a meta-analysis of two genome-wide association studies of breast cancer; one study consists of 1,657 cases and 2,029 controls genotyped with Illumina’s HumanOmni2.5 BeadChip and the other study included 3,016 cases and 2,745 controls genotyped using Illumina Human1M-Duo BeadChip. The top 18,376 single nucleotide polymorphisms (SNP) from the meta-analysis were replicated in the third study that consists of 1,984 African Americans cases and 2,939 controls. We found that SNP rs13074711, 26.5 Kb upstream of TNFSF10 at 3q26.21, was significantly associated with risk of oestrogen receptor (ER)-negative breast cancer (odds ratio [OR]=1.29, 95% CI: 1.18-1.40; P = 1.8 × 10 − 8). Functional annotations suggest that the TNFSF10 gene may be involved in breast cancer aetiology, but further functional experiments are needed. In addition, we confirmed SNP rs10069690 was the best indicator for ER-negative breast cancer at 5p15.33 (OR = 1.30; P = 2.4 × 10 − 10) and identified rs12998806 as the best indicator for ER-positive breast cancer at 2q35 (OR = 1.34; P = 2.2 × 10 − 8) for women of African ancestry. These findings demonstrated additional susceptibility alleles for breast cancer can be revealed in diverse populations and have important public health implications in building race/ethnicity-specific risk prediction model for breast cancer.

Although genome-wide association studies have identified over 100 risk loci that explain ∼33% of familial risk for prostate cancer (PrCa), their functional effects on risk remain largely unknown. Here we use genotype data from 59,089 men of European and African American ancestries combined with cell-type-specific epigenetic data to build a genomic atlas of single-nucleotide polymorphism (SNP) heritability in PrCa. We find significant differences in heritability between variants in prostate-relevant epigenetic marks defined in normal versus tumour tissue as well as between tissue and cell lines. The majority of SNP heritability lies in regions marked by H3k27 acetylation in prostate adenoc7arcinoma cell line (LNCaP) or by DNaseI hypersensitive sites in cancer cell lines. We find a high degree of similarity between European and African American ancestries suggesting a similar genetic architecture from common variation underlying PrCa risk. Our findings showcase the power of integrating functional annotation with genetic data to understand the genetic basis of PrCa.

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., (© The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Interpretation of biological mechanisms underlying genetic risk associations for prostate cancer is complicated by the relatively large number of risk variants (n = 100) and the thousands of surrogate SNPs in linkage disequilibrium. Here, we combined three distinct approaches: multiethnic fine-mapping, putative functional annotation (based upon epigenetic data and genome-encoded features), and expression quantitative trait loci (eQTL) analyses, in an attempt to reduce this complexity. We examined 67 risk regions using genotyping and imputation-based fine-mapping in populations of European (cases/controls: 8600/6946), African (cases/controls: 5327/5136), Japanese (cases/controls: 2563/4391) and Latino (cases/controls: 1034/1046) ancestry. Markers at 55 regions passed a region-specific significance threshold (P-value cutoff range: 3.9 × 10(-4)-5.6 × 10(-3)) and in 30 regions we identified markers that were more significantly associated with risk than the previously reported variants in the multiethnic sample. Novel secondary signals (P < 5.0 × 10(-6)) were also detected in two regions (rs13062436/3q21 and rs17181170/3p12). Among 666 variants in the 55 regions with P-values within one order of magnitude of the most-associated marker, 193 variants (29%) in 48 regions overlapped with epigenetic or other putative functional marks. In 11 of the 55 regions, cis-eQTLs were detected with nearby genes. For 12 of the 55 regions (22%), the most significant region-specific, prostate-cancer associated variant represented the strongest candidate functional variant based on our annotations; the number of regions increased to 20 (36%) and 27 (49%) when examining the 2 and 3 most significantly associated variants in each region, respectively. These results have prioritized subsets of candidate variants for downstream functional evaluation., (© The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Height has an extremely polygenic pattern of inheritance. Genome-wide association studies (GWAS) have revealed hundreds of common variants that are associated with human height at genome-wide levels of significance. However, only a small fraction of phenotypic variation can be explained by the aggregate of these common variants. In a large study of African-American men and women (n = 14,419), we genotyped and analyzed 966,578 autosomal SNPs across the entire genome using a linear mixed model variance components approach implemented in the program GCTA (Yang et al Nat Genet 2010), and estimated an additive heritability of 44.7% (se: 3.7%) for this phenotype in a sample of evidently unrelated individuals. While this estimated value is similar to that given by Yang et al in their analyses, we remain concerned about two related issues: (1) whether in the complete absence of hidden relatedness, variance components methods have adequate power to estimate heritability when a very large number of SNPs are used in the analysis; and (2) whether estimation of heritability may be biased, in real studies, by low levels of residual hidden relatedness. We addressed the first question in a semi-analytic fashion by directly simulating the distribution of the score statistic for a test of zero heritability with and without low levels of relatedness. The second question was addressed by a very careful comparison of the behavior of estimated heritability for both observed (self-reported) height and simulated phenotypes compared to imputation R2 as a function of the number of SNPs used in the analysis. These simulations help to address the important question about whether today's GWAS SNPs will remain useful for imputing causal variants that are discovered using very large sample sizes in future studies of height, or whether the causal variants themselves will need to be genotyped de novo in order to build a prediction model that ultimately captures a large fraction of the variability of height, and by implication other complex phenotypes. Our overall conclusions are that when study sizes are quite large (5,000 or so) the additive heritability estimate for height is not apparently biased upwards using the linear mixed model; however there is evidence in our simulation that a very large number of causal variants (many thousands) each with very small effect on phenotypic variance will need to be discovered to fill the gap between the heritability explained by known versus unknown causal variants. We conclude that today's GWAS data will remain useful in the future for causal variant prediction, but that finding the causal variants that need to be predicted may be extremely laborious.

Blood typing across different racial groups has revealed that Caucasians predominantly test positive for the Duffy antigen/receptor for chemokines (DARC), while 70-95% of African-origin populations lack expression of DARC on their erythrocytes. Since men of African descent are known to have higher rates of prostate cancer (PC) and some animal studies have indicated anti-angiogenic effects associated with Duffy-positive mice, DARC-negativity may help to explain some of the racial differences in prostate tumorigenesis. The Prostate Cancer in a Black Population (PCBP) Study, a large case-control investigation including 1,007 incident PC cases and 1,005 controls, performed DARC testing on a subset of 1,295 participants (641 cases, 654 controls). The relationship between DARC expressivity and PC risk was evaluated using logistic regression models and findings are presented as odds ratios and 95% confidence intervals. More than three-quarters (76.5%) of African-Barbadian men lacked DARC expression, whereas almost three-fifths (59.3%) of White participants tested positive for the Duffy a and b alleles. DARC-negativity was not found to be associated with PC risk in the present investigation [OR 1.04, 95% CI (0.78, 1.37)], regardless of tumor grade. Findings from the PCBP study indicate that the majority of African-Barbadian men do not express DARC on their erythrocytes, yet absence of expression does not appear to be associated with PC development in this population.

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., (© 2014 UICC.)

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., (© 2014 Wiley Periodicals, Inc.)

Although family history of prostate cancer (PC) is an established risk factor for the disease, few studies have investigated this relationship among men with an African heritage. The Prostate Cancer in a Black Population (PCBP) study is a large, nationwide case-control study conducted in Barbados, West Indies from 2002 to 2011. In the PCBP study, a family history of PC in fathers or brothers was associated with a threefold increased risk of disease (OR = 3.04, 95 % CI (2.18, 4.22)) and a strong positive relationship was noted for the number of affected first degree relatives. Tumor grade did not generally influence the relationship between family history and PC. The magnitude of risks associated with having a father affected with the disease was slightly higher in the PCBP study compared to other populations. It remains unclear whether this finding is the result of an increased genetic susceptibility in African-Barbadian men.

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.

Genome-wide association studies (GWAS) have identified 36 loci associated with body mass index (BMI), predominantly in populations of European ancestry. We conducted a meta-analysis to examine the association of >3.2 million SNPs with BMI in 39,144 men and women of African ancestry and followed up the most significant associations in an additional 32,268 individuals of African ancestry. We identified one new locus at 5q33 (GALNT10, rs7708584, P = 3.4 × 10(-11)) and another at 7p15 when we included data from the GIANT consortium (MIR148A-NFE2L3, rs10261878, P = 1.2 × 10(-10)). We also found suggestive evidence of an association at a third locus at 6q16 in the African-ancestry sample (KLHL32, rs974417, P = 6.9 × 10(-8)). Thirty-two of the 36 previously established BMI variants showed directionally consistent effect estimates in our GWAS (binomial P = 9.7 × 10(-7)), five of which reached genome-wide significance. These findings provide strong support for shared BMI loci across populations, as well as for the utility of studying ancestrally diverse populations.

Although some investigations have assessed the barriers to prostate cancer screening among African-American men, limited data are available regarding such practices in similar African-origin populations. Key informant interviews were employed to obtain a range of perspectives pertaining to the healthcare practices of African-Barbadian men and to identify factors that obstruct prostate cancer screening in Barbados, West Indies. Gender-related perceptions were identified as a major obstruction to prostate cancer screening. Additionally, concerns about privacy, taking time away from work and mistrust of the medical community were reported as themes impeding the healthcare-seeking behaviors of African-Barbadian men. System-level barriers included limitations in access to care and ineffective dissemination of health information. Findings from this study suggest that targeted efforts aimed at modifying socio-cultural perceptions may assist in improving prostate cancer screening and general healthcare-seeking practices of African-Barbadian men and others who share similar beliefs.

Prostate cancer (PC) is the principal malignancy affecting African descent men in the Caribbean and the USA. Disparities in incidence, prevalence, and mortality in these populations are poorly understood. We evaluated the urologic characteristics and sexual behaviors of men with histologically confirmed PC (cases) and age-matched controls in the nationwide Prostate Cancer in a Black Population (PCBP) study conducted in Barbados. Cases were around 1.5 to 3 times more likely to report symptoms of prostatic enlargement, hematuria/hematospermia, and previous prostatitis. Sexually transmitted infections (STIs) were similar among cases (24.5%) and controls (26.7%). First sexual intercourse before the age of 16 was associated with an increased likelihood of both low- (Gleason score < 7; OR 1.63; 95% CI: 1.03-1.66) and high-grade PC (Gleason score ≥ 7; OR 1.82; 1.11-2.99). PC risk decreased with later age of sexual debut (P-trend = 0.004). More lifetime sexual partners was associated with increased odds of high grade PC (P-trend = 0.02). The contribution of sexual behaviors to the development and the outcomes of PC is likely due to multiple mechanisms, and further study will be necessary to elucidate the underlying pathophysiologic mechanisms in this and similar populations.

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.

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.

Background: The relationship between central adiposity and prostate cancer remains unclear., Methods: This report includes 963 newly diagnosed cases of histologically confirmed prostate cancer and 941 randomly selected age-matched controls ascertained from the population-based Prostate Cancer in a Black Population study conducted between July 2002 and January 2011 in Barbados, West Indies. Trained nurse interviewers obtained data on height, weight, waist and hip circumferences, family and medical history, and lifestyle factors. ORs and 95% confidence intervals (CI) were used to assess associations between anthropometric measures and prostate cancer., Results: A two-fold increased risk of prostate cancer was found among men in the highest quartile of waist-hip ratio compared with those in the lowest quartile (OR = 2.11, 95% CI, 1.54-2.88). Similarly, men with the largest waist circumferences had an OR of 1.84 (95% CI, 1.19-2.85) compared with those with the smallest waist sizes., Conclusions: These results suggest that measures of central rather than global adiposity may be more predictive of prostate cancer, especially in westernized African populations, where patterns of visceral fat distribution are different than other groups., Impact: The findings highlight the need to further elucidate the mechanisms underlying the relationship between central adiposity and prostate cancer in populations of predominantly African descent.

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.

Background: Epidemiologic studies have reported a positive association between type 2 diabetes (T2D) and breast cancer risk, independent of body weight., Methods: We investigated 40 genetic variants known to be associated with T2D in relation to breast cancer risk among 2,651 breast cancer cases and 2,520 controls of African or European ancestry that were pooled from seven studies., Results: We found that two T2D risk alleles in Caucasian women (rs5945326-G, rs12518099-C) and one in women of African ancestry (rs7578597-T) were positively associated with breast cancer risk at a nominal significance level of 0.05, whereas two T2D risk alleles were inversely associated with breast cancer risk in Caucasian women (rs1111875-C, rs10923931-T). The composite T2D susceptibility score (the number of risk allele) was not significantly associated with breast cancer risk., Conclusion: The association between established T2D genetic susceptibility variants and breast cancer risk in women of African or European ancestry is likely weak, if it does exist., Impact: The pleiotropic effects of known T2D risk alleles cannot explain the association between T2D and breast cancer risk., (©2012 AACR.)

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.

The purpose of this study was to confirm previously reported associations of common variants in or near CDC7/TGFBR3, ZP4, SRBD1, ELOVL5, CAV1/CAV2, TLR4, CDKN2B, CDKN2B-AS1, ATOH7, PLXDC2, TMTC2, SIX1, and CARD10, with primary open angle glaucoma (POAG) in the Afro-Caribbean population of Barbados, West Indies. A total of 437 unrelated subjects from the Barbados Family Study of Open Angle Glaucoma (BFSG), including 272 with POAG and 165 unaffected individuals were included in this study. Eighteen SNPs were genotyped by using the multiplex SNaPshot method. Allelic, genotypic and model-based (dominant, recessive, and additive) associations of the SNPs with POAG were analyzed using Chi-squared tests and logistic regression. SNP rs1063192 (near CDKN2B) was found to be significantly associated with POAG (allelic P = 0.0008, genotypic P = 0.0029), and the minor allele C of rs1063192 was protective against POAG (OR = 0.39; 95%CI = 0.22-0.69). Suggestive association was also noted for rs7916697 (near ATHO7, allelic P = 0.0096, genotypic P = 0.01) with the minor allele being protective (OR = 0.67; 95% CI = 0.50-0.91), although this finding did not withstand correction for multiple testing. However, a significant interactive effect on POAG risk was identified between rs1063192 and rs7916697 (P-interaction = 2.80 × 10(-5)). Individuals with the rs1063192 protective genotype CC or CT and also rs7916697 genotypes GG or GA show a significantly decreased risk of POAG (OR = 0.17, 95%CI: 0.07-0.41). Our study confirms the significant association between SNP rs1063192 (CDKN2B, previously shown to influence vertical cup-to-disc ratio and POAG at 9p21) and POAG in the Afro-Caribbean population of Barbados. The minor allele of rs1063192 interacts with that of rs7916697 (ATOH7)) to reduce POAG risk. Our results also suggest that rs1063912 is a common protective variant for POAG in populations of African as well as European descent.

Purpose: To evaluate: (i) the relationship between intraocular pressure (IOP) reduction attained with a fixed treatment protocol and the untreated IOP level; (ii) the consistency of IOP reduction over time; and (iii) whether there is a threshold pretreatment IOP level below which IOP reduction might be less effective. Results are based on 128 patients with glaucoma with field defects, who were randomized to the treatment arm of the Early Manifest Glaucoma Trial (EMGT)., Methods: The EMGT fixed treatment protocol consisted of 360° laser trabeculoplasty and topical betaxolol eye drops B.I.D. Treatment was unchanged as long as progression did not occur. Analyses assessed the initial IOP reduction after 3 months and also the mean reduction based on all follow-up values; IOP changes over time were evaluated with linear regression analysis. Factors influencing initial and mean IOP reduction were also explored using linear models., Results: Mean age at baseline was 68 years, and untreated baseline IOP ranged from 13 to 30.5 mmHg. On average, eyes with higher baseline IOP experienced larger pressure reductions than eyes with lower baseline IOP, whether expressed in mmHg or as percentages. Each mmHg of higher baseline IOP was associated with approximately 0.6 mmHg larger IOP reduction. IOP changed little over time, with 66% of patients changing less than 0.5 mmHg/year, and only 13% (17/128) changing >1.0 mmHg/year. The treatment protocol did not achieve any average IOP reduction in eyes with baseline pressures ≤ 15 mmHg. Factors related to more IOP reduction at 3 months were higher baseline IOP and positive refractive error, while higher baseline IOP and male gender (more reduction) and cardiovascular disease history (less reduction) were associated with mean IOP on treatment., Conclusion: With a fixed treatment protocol, the IOP reduction achieved depended very strongly on baseline untreated IOP levels. There seemed to be a lower threshold around 15 mmHg, where therapy did not result in any reduction of IOP. Our results suggest that when effects of IOP-lowering treatment are reported, whether expressed in mmHg or as a percentage of untreated pressure levels, the baseline IOP levels should be specified as well., (© 2010 The Authors. Journal compilation © 2010 Acta Ophthalmol.)