Objective: To compare all-cause-mortality in screening-detected prostate cancer cases versus non-cases after a median 12.2-year follow-up. Methods: In this prospective, population-based study of 3089 Afro-Caribbean men aged 40–79 years in Tobago, Trinidad and Tobago, West Indies, all men were screened for prostate cancer (serum prostate specific antigen and/or digital rectal exam) one to three times between 1997and 2007 and followed for mortality to 2012. Among 502 men diagnosed with prostate cancer, 81 younger men underwent radical retropubic prostatectomy. Minimal treatment was available for older men. Survival curves compared all-cause-mortality in cases versus non-cases within 10-year age groups at first screening. Results: There were 350 all-cause-deaths over 34 089 person-years of follow-up. All-cause-survivalcurves in men aged 60 years or above at first screening did not diverge between casesand non-cases until after 10–12 years of follow-up (p > 0.36). In contrast, among men first screened at age 50–59 years, survival was lower in cases, with survival curves diverging at seven years (p = 0.003). Survival in men aged 50–59 years who underwent prostatectomy was similar to survival in non-cases (p = 0.63). Conclusion: Among men aged 60 years or above, the absence of excess all-cause-mortality among screening-detected prostate cancer cases provides argument against the utility of routine prostate cancer screening in this older population of African descent. However, the significantly poorer survival in men aged 50–59 years with screening-detected prostate cancer, compared with screened men without prostate cancer, along with the potential for prostate cancer treatment to improve survival, supports the continuation of prostate cancer screening in this age group, pending further research to assess the risks and benefits.
We tested if serum lipid and lipoprotein cholesterol levels are associated with longitudinal measures of bone mineral density (BMD) in 1289 African ancestry men. After 6 years of mean follow-up, men with clinically optimal levels of low-density lipoprotein (LDL), high-density lipoprotein (HDL), or triglycerides at baseline experienced the greatest BMD loss, independent of potential confounding factors (all p < 0.05).Studies of lipid and lipoprotein cholesterol associations with bone mineral density (BMD) and bone loss have been inconclusive, and longitudinal data are sparse. Therefore, the aim of this study was to test if fasting serum lipid and lipoprotein cholesterol levels are associated with areal and volumetric BMD and BMD change.We determined the association of serum triglycerides, high-density lipoprotein (HDL), and low-density lipoprotein (LDL) cholesterol concentrations with cross-sectional and longitudinal (mean follow-up, 6.1 years) measures of BMD in a cohort of 1289 in African ancestry men (mean age, 56.4 years). Fasting serum triglycerides, HDL, and LDL were measured at baseline concurrent with BMD assessments. Dual-energy X-ray absorptiometry was used to quantify integral hip BMD, and peripheral quantitative computed tomography at the radius and tibia was used to quantify volumetric BMD. Men were categorized as optimal, borderline, or high risk for triglyceride, HDL, and LDL concentrations based on Adult Treatment Panel III guidelines.Lower serum triglyceride or LDL and higher HDL concentrations were associated with lower trabecular BMD at baseline (all p < 0.05). Similarly, men classified as having optimal levels of LDL, HDL, or triglycerides at baseline experienced the greatest integral BMD loss at the hip and trabecular BMD loss at the tibia (all p < 0.05), independent of potential confounding factors.We found that clinically optimal serum lipid and lipoprotein cholesterol concentrations were associated with accelerated bone loss among Afro-Caribbean men. Further studies are needed to better understand the mechanisms involved and potential clinical significance of these findings.
We tested for association between cortical and trabecular volumetric bone mineral density (vBMD) with abdominal aortic calcification (AAC) prevalence in 278 Afro-Caribbean men. AAC was present in 68.3 % of the men. Greater cortical, but not trabecular, vBMD was associated with significantly decreased odds of AAC independent of traditional risk factors.
We determined factors associated with serum sclerostin in 446 Afro-Caribbean family members. Age, weight, sex, diabetes and kidney function were associated with sclerostin. Sclerostin was heritable, and nine SNPs in the SOST gene region were associated with sclerostin. Variation in serum sclerostin is a heritable factor that is determined by both genetic and environmental factors. Sclerostin, encoded by the SOST gene, is a Wnt inhibitor that regulates bone mineralization and is a candidate gene locus for osteoporosis. However, little is known about the genetic and non-genetic sources of inter-individual variation in serum sclerostin levels. Serum sclerostin was measured in 446 Afro-Caribbean men and women aged 18+ from seven large, multigenerational families (mean family size, 64; 3,840 relative pairs). Thirty-six common single nucleotide polymorphisms (SNP) were genotyped within a 100 kb region encompassing the gene encoding sclerostin (SOST). Genetic and non-genetic factors were tested for association with serum sclerostin. Mean serum sclerostin was 41.3 pmol/l and was greater in men than in women (P < 0.05). Factors associated with higher serum sclerostin were increased age and body weight, male sex, diabetes and decreased glomerular filtration rate, which collectively accounted for 25.4 % of its variation. Residual genetic heritability of serum sclerostin was 0.393 (P < 0.0001). Nine SNPs reached nominal significance with sclerostin. Three of those nine SNPs represented independent association signals (rs851056, rs41455049 and rs9909172), which accounted for 7.8 % of the phenotypic variation in sclerostin, although none of these SNPs surpassed a Bonferroni correction for multiple comparisons. Serum sclerostin is a heritable trait that is also determined by environmental factors including age, sex, adiposity, diabetes and kidney function. Three independent common SNPs within the SOST region may collectively account for a significant proportion of the variation in serum sclerostin.
To determine whether there are race/ethnic differences in bone mineral density (BMD) by fracture history in men aged 65 years and older, we performed cross-sectional analysis in five large independent cohorts. Low BMD was associated with a higher prevalence of fracture in all cohorts, and the magnitude of the BMD differences by fracture status was similar across groups.
OBJECTIVE:When compared with other ethnic groups, African ancestry individuals have lower triglycerides and higher High-density lipoprotein cholesterol (HDL-C) levels, although the mechanisms for these differences remain unclear. A comprehensive array of factors potentially related to fasting serum lipid and lipoprotein levels in African ancestry men was evaluated.DESIGN AND METHODS:Men (1,821) underwent dual-energy X-ray absorptiometry measures of total body fat and quantitative computed tomography assessments of calf skeletal muscle adiposity [subcutaneous and intermuscular adipose tissue (AT), and muscle density as a measure of intra-muscular AT].RESULTS:Multivariable linear regression analysis identified age (-), total body fat (+), subcutaneous AT (-), fasting glucose (+), fasting insulin (+), diastolic blood pressure (+), and non-African ancestry (+) as independent correlates of triglycerides (all P < 0.05). Total body fat (+), intra-muscular AT (-), and diastolic blood pressure (+) were independent correlates of Low-density lipoprotein cholesterol (LDL-C) (all P < 0.001). Age (+), waist circumference (-), fasting insulin (-), physical activity (+), and alcohol intake (+) were independent correlates of HDL-C (all P < 0.05).CONCLUSIONS:A novel relationship between skeletal muscle adiposity and serum lipid and lipoprotein levels in African ancestry men, independent of total and central adiposity was illuminated. In African ancestry populations, genetic factors are likely a significant determinant of triglycerides levels.
Osteocalcin is a major component of bone matrix. Concentrations of total, carboxylated, and uncarboxylated osteocalcin, are highly heritable and genetically correlated with bone mineral content (BMC) within African ancestry families.
We examined the association of serum 25-hydroxyvitamin D [25(OH)D] with indices of bone quality in older men. Positive associations for 25(OH)D and bone mineral density, content, cortical thickness, and axial and polar strength strain indices were observed among Caucasians; however, among men of African descent findings were either null or negative.
We compared rates of BMD decline in older men of diverse ethnic backgroud. The rate of bone loss was statistically equivalent between men of African and Caucasian descent.
African ancestry individuals have a more favorable lipoprotein profile than Caucasians, although the mechanisms for these differences remain unclear. We measured fasting serum lipoproteins and genotyped 768 tagging or potentially functional single nucleotide polymorphisms (SNPs) across 33 candidate gene regions in 401 Afro-Caribbeans older than 18 years belonging to 7 multi-generational pedigrees (mean family size 51, range 21–113, 3,426 relative pairs). All lipoproteins were significantly heritable (P < 0.05). Gender-specific analysis showed that heritability for triglycerides was much higher (P < 0.01) in women than in men (women, 0.62 ± 0.18, P < 0.01; men, 0.13 ± 0.17, P > 0.10), but the heritability for LDL cholesterol (LDL-C) was higher (P < 0.05) in men than in women (men, 0.79 ± 0.21, P < 0.01; women, 0.39 ± 0.12, P < 0.01). The top 14 SNPs that passed the false discovery rate threshold in the families were then tested for replication in an independent population-based sample of 1,750 Afro-Caribbean men aged 40+ years. Our results revealed significant associations for three SNPs in two genes (rs5929 and rs6511720 in LDLR and rs7517090 in PCSK9) and LDL-C in both the family study and in the replication study. Our findings suggest that LDLR and PCSK9 variants may contribute to a variation in LDL-C among African ancestry individuals. Future sequencing and functional studies of these loci may advance our understanding of genetic factors contributing to LDL-C in African ancestry populations.
Correlates of BMD were examined in a cross-sectional analysis of men of West African ancestry. BMD, measured at the total hip and the femoral neck subregion, was associated with age, anthropometric, lifestyle, and medical factors in multiple linear regression models. These models explained 25–27% of the variability in total hip and femoral neck BMD, respectively, and 13% of the variability in estimated volumetric BMD.
Abstract Human papillomavirus (HPV), a sexually transmitted virus causes cervical carcinomas, and is associated with ∼36% of oropharyngeal tumours where HPV16 is the predominant genotype. The cervical cancer incidence rate in Trinidad and Tobago is about two times higher than the worldwide rate. We have for the first time determined the prevalence and type distribution of cervical HPV infections among cancer-free Afro-Caribbean women from Tobago, and compared it with the HPV subtypes observed in their oral cavity. Thirty-five per cent of the women were cervical HPV positive. The most common high-risk type detected in the cervix was HPV45 rather than HPV16 and 18. The prevalence of HPV infection in the oral mucosa was 6.6%. The distribution of HPV genotypes in healthy Tobagonian women is different from that reported in studies conducted in European and North American populations. This may have important implications for vaccine introduction in this and other Afro-Caribbean countries.