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1.
Prostate ; 80(15): 1365-1372, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32894795

RESUMO

BACKGROUND: Prostate cancer (PC) risk increases with African ancestry and a history of sexually transmitted infections (STIs). Also, single-nucleotide polymorphisms (SNPs) in toll-like receptor (TLR) genes influence PC risk. This pilot study explores interactions between STIs and TLR-related SNPs in relation to PC risk among Jamaican men. METHODS: This case-control study evaluates two TLR related SNPs in 356 Jamaican men (194 controls and 162 cases) with or without history of STIs using stepwise penalized logistic regression in multivariable analyses. RESULTS: Age (odds ratio [OR] = 1.08; 95% confidence interval [CI]: 1.04-1>.12; p < .001) and IRF3_rs2304206 GG genotype (OR = 0.47; 95% CI: 0.29-0<.78; p = .003) modulated PC risk in people with history of STIs. In the population with no history of STIs, resulting interactions between risk factors did not survive correction for multiple hypothesis testing. CONCLUSION: Overall, an interaction between the IFR3_rs2304206 variant and a history of exposure to STIs leads to greater decrease of PC risk than the presence of polymorphic genotype alone. These findings are suggestive and require further validation. Identification of gene variants along with detection of lifestyle behaviors may contribute to identification of men at a greater risk of PC development in the population.


Assuntos
Predisposição Genética para Doença , Genótipo , Polimorfismo de Nucleotídeo Único , Neoplasias da Próstata/etiologia , Infecções Sexualmente Transmissíveis/complicações , Receptores Toll-Like/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Humanos , Jamaica , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , Medição de Risco , Fatores de Risco
2.
Blood Cells Mol Dis ; 73: 1-8, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30120022

RESUMO

Patients with sickle cell disease (SCD) display puzzling inter-individual phenotypic heterogeneity, conceivably related to inherent differences in antioxidant protection, hemoglobin binding, bilirubin catabolism and methyl group handling. Therefore, we explored putative associations between clinically important phenotypic measures and functional polymorphisms within specific candidate genes encoding glutathione S-transferase, haptoglobin, uridine 5'-diphospho-glucuronosyltransferase 1A1, methyl tetrahydrofolate reductase, 5-methyltetrahydrofolate-homocysteine methyltransferase, and cystathionine beta-synthase. Two-hundred and thirty SCD participants (mean age 25.1 ±â€¯2.8) were recruited from Jamaica's Annual Sickle Cell Unit Cohort Review - two-hundred and five had homozygous hemoglobin SS (HbSS) disease, twenty-five had hemoglobin SC (HbSC) disease. Regression analyses revealed some novel genotype-phenotype associations. HbSC participants had significantly lower mean lactate dehydrogenase (p = 0.01) and glutathione (p < 0.001) values than HbSS participants. Glutathione S-transferase P1 (GSTP1) was significantly associated with mean corpuscular hemoglobin concentration using univariate (p = 0.044) and multivariable regression (p = 0.012). 5-methyltetrahydrofolate-homocysteine methyltransferase (MTR) was significantly associated with hemoglobin F % using univariate (p = 0.010) and multivariable regression (p = 0.009). In conclusion, this exploratory cross-sectional study generated novel, useable, and informative genotype-phenotype estimates of association, but larger studies are needed to determine whether these specific variants are related to inter-individual phenotypic variability in SCD.


Assuntos
Anemia Falciforme/epidemiologia , Estudos de Associação Genética , Adulto , Anemia Falciforme/genética , Anemia Falciforme/patologia , Estudos Transversais , Enzimas/genética , Doença da Hemoglobina SC , Hemoglobina Falciforme , Humanos , Jamaica , Polimorfismo Genético , Análise de Regressão
3.
PLoS One ; 13(6): e0198626, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29879181

RESUMO

AIMS/HYPOTHESES: We hypothesized that there is decreased synthesis of glutathione (GSH) in type 2 diabetes (T2DM) especially in the presence of microvascular complications, and this is dependent on the degree of hyperglycemia. METHODS: In this case-control study, we recruited 16 patients with T2DM (7 without and 9 with microvascular complications), and 8 age- and sex-matched non-diabetic controls. We measured GSH synthesis rate using an infusion of [2H2]-glycine as isotopic tracer and collection of blood samples for liquid chromatography mass spectrometric analysis. RESULTS: Compared to the controls, T2DM patients had lower erythrocyte GSH concentrations (0.90 ± 0.42 vs. 0.35 ± 0.30 mmol/L; P = 0.001) and absolute synthesis rates (1.03 ± 0.55 vs. 0.50 ± 0.69 mmol/L/day; P = 0.01), but not fractional synthesis rates (114 ± 45 vs. 143 ± 82%/day; P = 0.07). The magnitudes of changes in patients with complications were greater for both GSH concentrations and absolute synthesis rates (P-values ≤ 0.01) compared to controls. There were no differences in GSH concentrations and synthesis rates between T2DM patients with and without complications (P-values > 0.1). Fasting glucose and HbA1c did not correlate with GSH concentration or synthesis rates (P-values > 0.17). CONCLUSIONS: Compared to non-diabetic controls, patients with T2DM have glutathione deficiency, especially if they have microvascular complications. This is probably due to reduced synthesis and increased irreversible utilization by non-glycemic mechanisms.


Assuntos
Glicemia , Diabetes Mellitus Tipo 2/metabolismo , Angiopatias Diabéticas/metabolismo , Glutationa/metabolismo , Microvasos/patologia , Adulto , Estudos de Casos e Controles , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/complicações , Angiopatias Diabéticas/sangue , Angiopatias Diabéticas/etiologia , Angiopatias Diabéticas/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
4.
Eur J Haematol ; 100(2): 147-153, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29114966

RESUMO

OBJECTIVES: To explore putative associations between specific variants in either the glutathione S-transferase (GST), haptoglobin (HP) or uridine 5'-diphospho-glucuronosyltransferase 1A1 (UGT1A1) genes and clinically important phenotypes in sickle cell anaemia (HbSS). METHODS: 371 HbSS participants were recruited from the Sickle Cell Clinic of the Sickle Cell Unit at the University of the West Indies, Kingston, Jamaica. Markers within four GST superfamily genes, the HP gene and the UGT1A1 gene were analysed using PCR-based assays. RESULTS: Multivariable regression revealed statistically significant associations between the GSTP1 Ile105Val heterozygote and HbA2 levels (P = .016), HbF percentage (P = .001), MCH concentration (P = .028) and reticulocyte count (P = .032), while the GSTM3 D/D homozygote was significantly associated with HbA2 levels (P = .032). The UGT1A1 (TA)6 /(TA)8 heterozygote showed statistically significant associations with HbA2 levels (P = .019), HbF percentage (P < .001), haemoglobin levels (P = .008), PCV values (P = .007) and RBC counts (P = .041). CONCLUSION: This exploratory cross-sectional study has generated novel and informative genotype-phenotype estimates of association, but larger studies are needed to determine whether these specific variants within the GST, UGT1A1 and HP genes are related to interindividual phenotypic variability in HbSS.


Assuntos
Anemia Falciforme/diagnóstico , Anemia Falciforme/genética , Variação Genética , Glucuronosiltransferase/genética , Glutationa Transferase/genética , Haptoglobinas/genética , Fenótipo , Adulto , Biomarcadores , Estudos Transversais , Índices de Eritrócitos , Feminino , Estudos de Associação Genética , Hemoglobina Falciforme/genética , Humanos , Jamaica , Masculino , Pessoa de Meia-Idade , Adulto Jovem
5.
Gene ; 636: 96-102, 2017 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-28903065

RESUMO

African ancestry and obesity are associated with higher risk of prostate cancer (PC). In a pilot study, we explored interactions between obesity (as measured by waist to hip ratio (WHR)) and inflammatory SNPs in relation to PC risk among Jamaican men. This study evaluated 87 chemokine and cytokine associated SNPs in obese and normal weight cases (N=109) and controls (N=102) using a stepwise penalized logistic regression approach in multivariable analyses. Upon stratification by WHR (normal weight (WHR<0.90) or obese (WHR≥0.90)), inheritance of CCR6 rs2023305 AG+GG (OR=1.75, p=0.007), CCR9 rs7613548 AG+GG (OR=1.71, p=0.012) and IL10ra rs2229113 AG+GG (OR=1.45, p=0.01) genotypes was associated with increase in overall or low grade (Gleason score<7) PC risk among normal weight men. These odds were elevated among obese men who possessed the CCR5 rs1799987 AG+GG (OR=1.95, p=0.003) and RNASEL rs12135247 CT+TT genotypes (OR=1.59, p=0.05). CCR7 rs3136685 AG+GG (p=0.032) was associated with a 1.52-1.70 fold increase in the risk of high grade cancer (Gleason score≥7) among obese men. CCR7 variant emerged as an important factor associated with high grade PC risk among obese men in our analyses. Overall, genetic loci found significant in normal weight men were not significant in obese men and vice-versa, partially explaining the role of obesity on PC risk among black men. Also, older age was an important risk factor both in normal weight and obese men but only with regard to low grade PC. Associations of inflammatory SNPs with obesity are suggestive and require further validation in larger cohorts to help develop an understanding of PC risk among obese and non-obese men of African descent.


Assuntos
Tamanho Corporal , Obesidade/complicações , Polimorfismo de Nucleotídeo Único , Neoplasias da Próstata/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , População Negra/genética , Estudos de Casos e Controles , Quimiocinas/genética , Citocinas/genética , Interação Gene-Ambiente , Humanos , Mediadores da Inflamação , Jamaica , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Neoplasias da Próstata/etiologia , Fatores de Risco
6.
Cancer Causes Control ; 28(11): 1313-1321, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28864928

RESUMO

PURPOSE: To investigate the association between serum cholesterol and prostate cancer and whether any effect may be mediated through inflammatory markers. METHODS: Data from a case-control study of 40-80 years old Jamaican male patients (229 cases; 252 controls) were used. Cases had incident histologically-confirmed prostate cancer and controls were men with normal digital rectal examination and prostate-specific antigen (PSA) < 4 µg/L or free: total PSA > 0.15 obtained from the same clinic. Total and HDL cholesterol, interleukin-6 (IL-6), and C-reactive protein (CRP) were measured from a non-fasting sample. Multivariable logistic regression models were used to evaluate the associations between these factors and prostate cancer, adjusting for age, body mass index, waist circumference, family history of prostate cancer, diabetes, hypertension, use of cholesterol-lowering drugs, and smoking. RESULTS: Total cholesterol [Mean (cases, 4.71 ± 1.07; controls, 4.64 ± 1.07 mmol/L)], CRP [median (cases, 2.11; controls, 2.09 µg/ml)], and IL-6: [median (cases, 3.34; controls, 3.24 pg/ml)] did not differ by PCA status. Higher total cholesterol was associated with an increased risk of low-grade disease after adjusting for potential confounders [multivariable-adjusted OR (95% CI): tertile 2: 3.32(1.66, 6.45), tertile 3: 2.14(1.07, 4.32)]. Total cholesterol was unrelated to overall prostate cancer or high-grade disease. There was no significant association between HDL cholesterol or any of the inflammatory markers with prostate cancer. CONCLUSIONS: Increasing total cholesterol but not inflammatory markers were associated with low-grade prostate cancer in Caribbean men.


Assuntos
Colesterol/sangue , Neoplasias da Próstata/sangue , Neoplasias da Próstata/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Proteína C-Reativa/análise , Estudos de Casos e Controles , HDL-Colesterol/sangue , Humanos , Interleucina-6/sangue , Jamaica/epidemiologia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Antígeno Prostático Específico/sangue
7.
Maturitas ; 82(2): 170-5, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26223581

RESUMO

BACKGROUND: Isoflavones and lignans are phytoestrogens, and therefore, are able to bind to and activate estrogen receptors. The resultant estrogenic or antiestrogenic effect is dependent on the concentration of these phytoestrogens relative to endogenous estrogens and the site of their action, among others. Thus, isoflavones and lignans act as selective estrogen receptor modulators; having a beneficial effect in some tissues while simultaneously causing deleterious changes in others. OBJECTIVE: This case-control study investigates the relationship between urinary concentrations of genistein, daidzein, equol, and enterolactone, and the presence of uterine leiomyomas (fibroids) in Jamaican women. DESIGN: Phytoestrogen concentration in spot urine samples from 157 uterine fibroid cases and 171 fibroid-free controls diagnosed by ultrasonography, were assessed by Time-resolved Fluoroimmnoassay. Statistical evaluations were performed using SPSS 12.0. RESULTS: The median concentration of urinary enterolactone was significantly different between uterine fibroid cases and controls (p=0.029). However, this was not observed to affect risk of uterine fibroid, as trends across quartiles of urine enterolactone did not differ significantly between cases and controls. Median urinary genistein (p=0.510), daidzein (p=0.838), equol (p=0.621), total isoflavones (0.510) and total phytoestrogens (p=0.084) were similar for both groups. Binary logistic regression analysis of quartiles of urine genistein, daidzein, equol, enterolactone, total isoflavones, and total phytoestrogens showed no association with uterine fibroid. CONCLUSIONS: Uterine fibroid cases had a higher median urine concentration of enterolactone compared with controls. However, this was not observed to affect ones risk of fibroid. Neither was urine genistein, daidzein, equol total isoflavones, and total phytoestrogens observed to be associated with risk of uterine fibroid.


Assuntos
Isoflavonas/urina , Leiomioma/epidemiologia , Fitoestrógenos/urina , Neoplasias Uterinas/epidemiologia , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Jamaica/epidemiologia , Leiomioma/etiologia , Leiomioma/urina , Fatores de Risco , Neoplasias Uterinas/etiologia , Neoplasias Uterinas/urina , Saúde da Mulher
8.
Cancer Med ; 4(6): 925-35, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25858172

RESUMO

Circulating 25-hydroxyvitamin D [25(OH)D] concentrations have been associated with both higher and lower risk of prostate cancer (PCa), whereas elevated levels of circulating calcium has been related to higher risks. However, there are few studies that account for effects of both calcium and 25(OH)D concentrations on incident PCa in a black population. We examined these relationships in a case-control study of men 40-80 years old with newly diagnosed, histologically confirmed PCa in Jamaica, a tropical country. Mean serum calcium concentrations was higher among cases (2.32 ± 0.19 mmol/L) than controls, (2.27 ± 0.30 mmol/L) (P = 0.023) however, there were no differences in 25(OH)D by cancer status (cases, 33.67 ± 12.71 ng/mL; controls (32.25 ± 12.59 ng/mL). Serum calcium was not correlated with 25(OH)D (partial correlation: r, 0.06; P = 0.287). Multivariable-adjusted models showed a positive linear relationship between PCa and serum calcium (OR, 1.12; CI, 1.00-1.25 per 0.1 nmol/L). Serum 25(OH)D concentration also showed a positive association with PCa (OR, 1.23; CI, 1.01-1.49 per 10 ng/mL). The odds of PCa in men with serum 25(OH)D tertile 2 was OR, 2.18; CI, 1.04-4.43 and OR, 2.47 CI, 1.20-4.90 for tertile 3 (P(trend) = 0.013). Dietary intakes of calcium showed no relationship with PCa. Despite the strong relationship between serum calcium and vitamin D the mechanism by which each affects prostate cancer risk in men of African ancestry needs additional investigation.


Assuntos
Cálcio/metabolismo , Neoplasias da Próstata/sangue , Vitamina D/análogos & derivados , Adulto , Idoso , Idoso de 80 Anos ou mais , População Negra/etnologia , Cálcio da Dieta/administração & dosagem , Estudos de Casos e Controles , Humanos , Jamaica/etnologia , Masculino , Pessoa de Meia-Idade , Neoplasias da Próstata/etnologia , Fatores de Risco , Vitamina D/metabolismo
9.
Hered Cancer Clin Pract ; 11(1): 19, 2013 Dec 23.
Artigo em Inglês | MEDLINE | ID: mdl-24359571

RESUMO

PURPOSE: Although case-control studies have evaluated the role of variant inflammatory-related loci in prostate cancer, their impact is virtually unknown among men of African descent. To address this, we evaluated the impact of inflammatory cytokine single nucleotide polymorphisms (SNPs) on prostate cancer risk for men of African descent. METHODS: Forty-four SNPs in inflammatory cytokine-associated genes were evaluated among 814 African-American and Jamaican men (279 prostate cancer cases and 535 controls) using Illumina's Golden gate genotyping system. Individual SNP effects were evaluated using logistic regression analysis. RESULTS: Four SNPs were modestly associated with prostate cancer after adjusting for age. In the total population, inheritance of the IL1R2 rs11886877 AA, IL8RB rs11574752 AA, TNF rs1800629 GA + AA, and TNF rs673 GA genotypes modestly increased prostate cancer risk by 1.45 to 11.7-fold relative to the referent genotype. Among U.S. men, age-adjusted dominant, recessive and additive genetic models for the IL1R2 rs11886877 locus were linked to an increase in prostate cancer susceptibility. However, these main effects did not persist after adjusting for multiple hypothesis testing. CONCLUSION: Our preliminary data does not strongly support the hypothesis that inflammatory-related sequence variants influence prostate cancer risk among men of African descent. However, further evaluation is needed to assess whether other variant inflammatory-related genes may contribute to prostate cancer risk and disease progression in larger and ethnically diverse multi-center studies.

10.
J Nat Sci Biol Med ; 4(2): 330-5, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24082727

RESUMO

BACKGROUND: Pre-eclampsia (PE) complicates approximately 5-7% of all pregnancies. This study investigates the effects of S-nitroso-N-acetylpenicillamine (SNAP) and S-nitrosoglutathione (GSNO) on the classical features of PE. MATERIALS AND METHODS: On day 14 of gestation, female Sprague-Dawley rats were separated into five groups and treated intravenously for 7 days as follows: (i) 0.3 mL 0.9% saline (control, n = 11); (ii) 50 mg/kg Body Weight (BW) N-nitro-L-arginine methyl ester (L-NAME) in 0.3 mL saline (n = 10); (iii) 50 mg/kg BW L-NAME and 8 mg/kg BW GSNO in 0.15 mL saline (n = 6); (iv) 50 mg/kg BW L-NAME in 0.15 mL saline and 8 mg/kg BW SNAP in 0.15 mL DMSO (n = 9); and (v) 0.15 mL DMSO and 0.15 mL saline (SNAP control, n = 7). Blood pressures were measured on day 14 through day 20, a 4-h urine sample was taken on day 20, and animals were sacrificed on day 21. Pups were counted and weighed individually. RESULTS: SNAP and GSNO significantly decreased systolic, diastolic, and mean arterial pressures in PE-induced rats from day 14 through day 20 (P < 0.05). Pup weights in SNAP and GSNO groups were higher than in L-NAME group but lower than in controls (P ≤ 0.001). SNAP and GSNO partially reversed growth retardation. CONCLUSION: Elevated blood pressure, proteinuria, and intrauterine growth restriction associated with PE were induced in Sprague-Dawley rats using L-NAME. These were partially reversed with the use of GSNO and SNAP. The mechanism of action of these S-nitrosothiols (RSNOs) should be further explored.

11.
Nutr Cancer ; 65(3): 367-74, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23530635

RESUMO

Studies of diet and prostate cancer have focused primarily on food and nutrients; however, dietary patterns examine the overall diet, particularly foods eaten in combination, and risk of disease. We evaluated the association of dietary patterns and prostate cancer and low- and high-grade subgroups in Jamaican men. In a case-control study, we enrolled 243 incident cases and 273 urology controls in Jamaican clinics, March 2005-July 2007. Dietary patterns were identified using principal component analysis. Four food patterns were identified: a "vegetable and legume" pattern, a "fast food" pattern, a "meat" pattern, and a "refined carbohydrate" pattern. Men in the highest tertile for the refined carbohydrate pattern, characterized by high intakes of rice, pasta, sugar sweetened beverages, and sweet baked foods were at increased risk of total prostate cancer [odds ratio (OR) = 2.02; 95% confidence interval (CI) = 1.05-3.87 (Ptrend = 0.029)] and low-grade disease [OR = 2.91; 95% CI = 1.18-7.13 (Ptrend = 0.019)] compared with men in the lowest tertile. The vegetable and legumes pattern (healthy), meat pattern, or fast food pattern were not associated with prostate cancer risk. These data suggest a carbohydrate dietary pattern high in refined carbohydrates may be a risk factor for prostate cancer in Jamaican men.


Assuntos
Dieta/efeitos adversos , Neoplasias da Próstata/etiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Índice de Massa Corporal , Estudos de Casos e Controles , Carboidratos da Dieta/efeitos adversos , Escolaridade , Ingestão de Energia , Exercício Físico , Humanos , Jamaica/epidemiologia , Masculino , Carne , Pessoa de Meia-Idade , Neoplasias da Próstata/epidemiologia , Neoplasias da Próstata/patologia , Fatores de Risco , Fumar
12.
Genes Nutr ; 8(2): 199-207, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23007265

RESUMO

Little is known about the role of folate and polymorphisms associated with folate metabolism on prostate cancer risk in populations of African origin. We examined the relationship between serum folate and prostate cancer and whether any association was modified by genetic polymorphisms for folate metabolism. The study was case-control in design and consisted of 218 men 40-80 years old with newly diagnosed, histologically confirmed prostate cancer and 236 cancer-free men attending the same urology clinics in Jamaica, March 2005-July 2007. Serum folate was measured by an immunoassay method and genomic DNA evaluated for MTHR (C677T and A1298C), MTRR A66G, and MTR A2756G polymorphisms. Mean serum folate concentration was higher among cases (12.3 ± 4.1 nmol/L) than controls (9.7 ± 4.2 nmol/L). Serum folate concentration showed a positive association with prostate cancer (OR, 4.41; CI, 2.52-7.72 per 10 nmol/L) regardless of grade. No interactions were observed between genotype and folate concentration, but a weak gene effect was observed for MTHFR A1298C and low-grade prostate cancer. Larger studies to investigate the role of gene-gene/gene-diet interactions in Black men are needed.

13.
Prostate ; 73(6): 668-76, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23129512

RESUMO

BACKGROUND: A meta and pooled analysis of published and unpublished case-control studies was performed to evaluate the association of CYP17 (rs743572) and CYP3A4 (rs2740574) polymorphisms and prostate cancer (PCa) in men from the USA, Caribbean, and Africa. METHODS: Eight publications (seven studies) and two unpublished studies for CYP17 included 1,580 subjects (559 cases and 1,021 controls) and eleven publications and three unpublished studies for CYP3A4 included 3,400 subjects (1,429 cases and 1,971 controls). RESULTS: Overall, the CYP17 heterozygous and homozygous variants were not associated with PCa, but they confer a 60% increased risk of PCa in a sub-group analysis restricted to African-American men (T/C + C/C, OR: 1.6, 95% CI: 1.1-2.4). No associations were observed for CYP3A4, overall and in stratified analyses for African-Americans and Africans. The pooled analysis suggests that after adjusting for study, age, PSA, and family history of PCa, CYP17 was associated with PCa for men of African ancestry (Adjusted OR: 3.5, 95% CI: 1.2-10.0). CONCLUSIONS: Our findings suggest that genetic factors involved in the androgen pathway play a role in PCa risk among men of African ancestry.


Assuntos
Negro ou Afro-Americano/genética , Negro ou Afro-Americano/estatística & dados numéricos , Citocromo P-450 CYP3A/genética , Neoplasias da Próstata/etnologia , Neoplasias da Próstata/genética , Esteroide 17-alfa-Hidroxilase/genética , Adulto , Idoso , Região do Caribe/epidemiologia , Estudos de Casos e Controles , Predisposição Genética para Doença/etnologia , Predisposição Genética para Doença/genética , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Nigéria/epidemiologia , Polimorfismo Genético/genética , Fatores de Risco , Programa de SEER/estatística & dados numéricos , Estados Unidos/epidemiologia
14.
Hered Cancer Clin Pract ; 10(1): 16, 2012 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-23168091

RESUMO

BACKGROUND: Chemokine and chemokine receptors play an essential role in tumorigenesis. Although chemokine-associated single nucleotide polymorphisms (SNPs) are associated with various cancers, their impact on prostate cancer (PCA) among men of African descent is unknown. Consequently, this study evaluated 43 chemokine-associated SNPs in relation to PCA risk. We hypothesized inheritance of variant chemokine-associated alleles may lead to alterations in PCA susceptibility, presumably due to variations in antitumor immune responses. METHODS: Sequence variants were evaluated in germ-line DNA samples from 814 African-American and Jamaican men (279 PCA cases and 535 controls) using Illumina's Goldengate genotyping system. RESULTS: Inheritance of CCL5 rs2107538 (AA, GA+AA) and rs3817655 (AA, AG, AG+AA) genotypes were linked with a 34-48% reduction in PCA risk. Additionally, the recessive and dominant models for CCR5 rs1799988 and CCR7 rs3136685 were associated with a 1.52-1.73 fold increase in PCA risk. Upon stratification, only CCL5 rs3817655 and CCR7 rs3136685 remained significant for the Jamaican and U.S. subgroups, respectively. CONCLUSIONS: In summary, CCL5 (rs2107538, rs3817655) and CCR5 (rs1799988) sequence variants significantly modified PCA susceptibility among men of African descent, even after adjusting for age and multiple comparisons. Our findings are only suggestive and require further evaluation and validation in relation to prostate cancer risk and ultimately disease progression, biochemical/disease recurrence and mortality in larger high-risk subgroups. Such efforts will help to identify genetic markers capable of explaining disproportionately high prostate cancer incidence, mortality, and morbidity rates among men of African descent.

15.
Cancer Causes Control ; 23(1): 23-33, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21984307

RESUMO

OBJECTIVE: To investigate the association of whole-blood fatty acids and reported intakes of fats with risk of prostate cancer (PCa). DESIGN: Case-control study of 209 men 40-80 years old with newly diagnosed, histologically confirmed prostate cancer and 226 cancer-free men attending the same urology clinics. Whole-blood fatty acid composition (mol%) was measured by gas chromatography and diet assessed by food frequency questionnaire. RESULTS: High whole-blood oleic acid composition (tertile 3 vs. tertile 1: OR, 0.37; CI, 0.14-0.0.98) and moderate palmitic acid proportions (tertile 2: OR, 0.29; CI, 0.12-0.70) (tertile 3: OR, 0.53; CI, 0.19-1.54) were inversely related to risk of PCa, whereas men with high linolenic acid proportions were at increased likelihood of PCa (tertile 3 vs. tertile 1: OR, 2.06; 1.29-3.27). Blood myristic, stearic and palmitoleic acids were not associated with PCa. Higher intakes of dietary MUFA were inversely related to prostate cancer (tertile 3 vs. tertile 1: OR, 0.39; CI 0.16-0.92). The principal source of dietary MUFA was avocado intake. Dietary intakes of other fats were not associated with PCa. CONCLUSIONS: Whole-blood and dietary MUFA reduced the risk of prostate cancer. The association may be related to avocado intakes. High blood linolenic acid was directly related to prostate cancer. These associations warrant further investigation.


Assuntos
Gorduras Insaturadas na Dieta/administração & dosagem , Ácidos Graxos Monoinsaturados/administração & dosagem , Ácidos Graxos/sangue , Ácido Oleico/sangue , Neoplasias da Próstata/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/sangue , Estudos de Casos e Controles , Comportamento Alimentar , Humanos , Jamaica , Masculino , Pessoa de Meia-Idade , Persea , Fatores de Risco , Ácido alfa-Linolênico/sangue
16.
Carcinogenesis ; 32(9): 1361-5, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21705483

RESUMO

Prostate cancer disparities have been reported in men of African descent who show the highest incidence, mortality, compared with other ethnic groups. Few studies have explored the genetic and environmental factors for prostate cancer in men of African ancestry. The glutathione-S-transferases family conjugates carcinogens before their excretion and is expressed in prostate tissue. This study addressed the role of GSTM1 and GSTT1 deletions on prostate cancer risk in populations of African descent. This multi-institutional case-control study gathered data from the Genetic Susceptibility to Environmental Carcinogens (GSEC) database, the African-Caribbean Cancer Consortium (AC3) and Men of African Descent and Carcinoma of the Prostate Consortium (MADCaP). The analysis included 10 studies (1715 cases and 2363 controls), five in African-Americans, three in African-Caribbean and two in African men. Both the GSTM1 and the GSTT1 deletions showed significant inverse associations with prostate cancer [odds ratio (OR): 0.90, 95% confidence interval (CI) 0.83-0.97 and OR 0.88, 95% CI: 0.82-0.96, respectively]. The association was restricted to Caribbean and African populations. A significant positive association was observed between GSTM1 deletion and prostate cancer in smokers in African-American studies (OR: 1.28, 95% CI: 1.01-1.56), whereas a reduced risk was observed in never-smokers (OR: 0.66, 95% CI: 0.46-0.95). The risk of prostate cancer increased across quartiles of pack-years among subjects carrying the deletion of GSTM1 but not among subjects carrying a functional GSTM1. Gene-environment interaction between smoking and GSTM1 may be involved in the etiology of prostate cancer in populations of African descent.


Assuntos
Negro ou Afro-Americano/genética , Predisposição Genética para Doença , Neoplasias da Próstata/genética , Idoso , Deleção de Genes , Glutationa Transferase/genética , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias da Próstata/etiologia , Fumar/efeitos adversos
17.
Cancer Causes Control ; 21(12): 2249-57, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-20924663

RESUMO

We evaluated the relationship of spot urinary concentrations of phytoestrogens with total prostate cancer and tumor grade in a hospital-based case-control study in Jamaica. Urine samples were analyzed for genistein, daidzein, equol (isoflavones), and enterolactone (lignan) among newly diagnosed cases (n = 175) and controls (n = 194). Urinary concentrations of enterolactone (lignan) were higher among cases. There were no significant differences in median concentrations of isoflavone excretion. Compared with non-producers of equol (reference tertile), men who produced equol were at decreased risk of total prostate cancer (tertile 2: OR, 0.42; CI, 0.23-0.75) (tertile 3: OR, 0.48; CI, 0.26-0.87) (p (trend), 0.020) and high-grade disease (tertile 2: OR, 0.31; CI, 0.15-0.61) (tertile 3: OR, 0.29; CI, 0.13-0.60) (p (trend), 0.001). Higher concentrations of enterolactone were positively related to total prostate cancer (OR, 1.85; CI, 1.01-3.44; p (trend), 0.027) as well as high-grade disease (OR, 2.46; CI, 1.11-5.46; p (trend), 0.023). There were no associations between urinary excretion of genistein and daidzein with risk of prostate cancer. Producers of equol (isoflavone) may be at reduced risk of total- and high-grade prostate cancer whereas enterolactone may increase the likelihood of disease.


Assuntos
Carcinoma/etiologia , Fitoestrógenos/urina , Neoplasias da Próstata/etiologia , Idoso , Carcinoma/epidemiologia , Carcinoma/urina , Estudos de Casos e Controles , Equol , Genisteína/urina , Humanos , Isoflavonas/urina , Jamaica/epidemiologia , Lignanas/urina , Masculino , Pessoa de Meia-Idade , Neoplasias da Próstata/epidemiologia , Neoplasias da Próstata/urina , Risco
18.
Cancer Causes Control ; 21(6): 909-17, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-20157773

RESUMO

We investigated the associations between body size and risk of prostate cancer in a hospital-based case-control study in Jamaica. Height, weight, waist, and hip circumference were measured at enrollment, and data collected on medical and lifestyle factors for newly diagnosed cases (n = 243) and controls (n = 275). Compared with men in the normal range of waist-hip ratio (WHR), men with WHR > or =0.95 were at greater risk of total prostate cancer (OR,1.72; CI, 1.01-3.00) and high-grade cancer (OR, 2.02; CI, 1.03-3.96). With additional control for BMI, the association with WHR remained significant for total prostate cancer (OR, 1.90; CI, 1.01-3.53) and high-grade disease (OR, 2.94; CI, 1.34-6.38). There was no association between waist circumference and cancer without control for BMI but after controlling for BMI, waist circumference >90 cm (OR, 2.45; CI, 1.01-5.94) and >102 cm (OR, 5.57; CI, 1.43-18.63) showed a dose-response relationship with high-grade disease. Height and BMI were not associated with risk of prostate cancer. Abdominal obesity may be associated with risk of high-grade prostate cancer. Risk may be greater in those with higher abdominal obesity relative to overall size. The results further highlight the importance of investigating relationships by characteristics of the tumor.


Assuntos
Tamanho Corporal/fisiologia , Abdome/patologia , Composição Corporal , Peso Corporal , Estudos de Casos e Controles , Humanos , Jamaica , Estilo de Vida , Masculino , Obesidade Abdominal , Neoplasias da Próstata/patologia , Fatores de Risco , Circunferência da Cintura , Relação Cintura-Quadril
19.
Infect Agent Cancer ; 4 Suppl 1: S11, 2009 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-19208202

RESUMO

BACKGROUND: Vaccines, that target human papillomavirus (HPV) high risk genotypes 16 and 18, have recently been developed. This study was aimed at determining genotypes commonly found in high-risk and multiple-HPV infections in Jamaican women. Two hundred and fifty three (253) women were enrolled in the study. Of these, 120 pregnant women, aged 15-44 years, were recruited from the Ante Natal Clinic at the University Hospital of the West Indies and 116 non-pregnant, aged 19-83, from a family practice in Western Jamaica. Cervical cell samples were collected from the women and HPV DNA was detected using Polymerase Chain Reaction and Reverse Line Hybridization. HPV genotypes were assessed in 236 women. Data were collected from January 2003 to October 2006. RESULTS: HPV DNA was detected in 87.7% (207/236) and of these 80.2% were positive for high-risk types. The most common high-risk HPV types were: HPV 45 (21.7%), HPV 58 (18.8%), HPV 16 (18.4%), HPV 35 (15.0%), HPV 18 (14.5%), HPV 52 (12.0%) and HPV 51(11.1%). Other high-risk types were present in frequencies of 1.4% - 7.2%.Multivariate regression analyses showed that bacterial vaginosis predicted the presence of multiple infections (OR 3.51; CI, 1.26-9.82) and that alcohol use (OR 0.31; CI, 0.15-0.85) and age at first sexual encounter (12-15 years: OR 3.56; CI, 1.41-9.12; 16-19 years, OR 3.53, CI, 1.22-10.23) were significantly associated with high risk infections. Cervical cytology was normal in the majority of women despite the presence of high-risk and multiple infections. CONCLUSION: HPV genotype distribution in this group of Jamaican women differs from the patterns found in Europe, North America and some parts of Asia. It may be necessary therefore to consider development of other vaccines which target genotypes found in our and similar populations. HPV genotyping as well as Pap smears should be considered.

20.
Infect Agent Cancer ; 4 Suppl 1: S5, 2009 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-19208210

RESUMO

BACKGROUND: Morbidity and mortality data highlight prostate cancer as the most commonly diagnosed neoplasm in Jamaican males. This report examines the association between dietary patterns and risk of prostate cancer in Jamaican men. MATERIALS AND METHODS: Case-control study of 204 histologically confirmed newly diagnosed prostate cancer cases and 204 individually matched urology clinic controls in Jamaica, 2004 - 2007. Diet was assessed by food frequency questionnaire. RESULTS: Factor analysis yielded four dietary patterns: (i) a "healthy" pattern of vegetables, fruits and peas and beans, (ii) a "carbohydrate" pattern with high loadings for white bread and refined cereals, (iii) "sugary foods and sweet baked products" pattern and (iv) a "organ meat and fast food pattern" with high loadings for high fat dessert, organ meat, fast food and salty snacks.Logistic regressions with the individual dietary patterns controlling for potential confounders showed no association between any of the food patterns and risk of prostate cancer. The healthy pattern showed an inverse non-significant association, whereas the carbohydrate pattern was positively and insignificantly related to prostate cancer. Analysis of all food patterns adjusting for each other revealed no association between food patterns and the risk of prostate cancer. CONCLUSION: Dietary patterns identified in our sample were not associated with risk of prostate cancer. Further investigations that better define cancer-free subjects and dietary measurements are needed to examine diet and prostate cancer outcomes.

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