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1.
Am J Clin Nutr ; 2020 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-31915809

RESUMO

BACKGROUND: Choline-related nutrients are dietary precursors of a gut microbial metabolite, trimethylamine-N-oxide, which has been linked to cardiometabolic diseases and related death. However, epidemiologic evidence on dietary choline and mortality remains limited, particularly among nonwhite populations. OBJECTIVES: This study aimed to investigate the associations of choline-related nutrients with cardiometabolic and all-cause mortality among black and white Americans and Chinese adults. METHODS: Included were 49,858 blacks, 23,766 whites, and 134,001 Chinese, aged 40-79 y, who participated in 3 prospective cohorts and lived ≥1 y after enrollment. Cox regression models were used to estimate HRs and 95% CIs for cardiometabolic [e.g., ischemic heart disease (IHD), stroke, and diabetes] and all-cause deaths. To account for multiple testing, P values < 0.003 were considered significant. RESULTS: Mean choline intake among blacks, whites, and Chinese was 404.1 mg/d, 362.0 mg/d, and 296.8 mg/d, respectively. During a median follow-up of 11.7 y, 28,673 deaths were identified, including 11,141 cardiometabolic deaths. After comprehensive adjustments, including for overall diet quality and disease history, total choline intake was associated with increased cardiometabolic mortality among blacks and Chinese (HR for highest compared with lowest quintile: 1.26; 95% CI: 1.13, 1.40 and HR: 1.23; 95% CI: 1.11, 1.38, respectively; both P-trend < 0.001); among whites, the association was weaker (HR: 1.12; 95% CI: 0.95, 1.33; P-trend = 0.02). Total choline intake was also associated with diabetes and all-cause mortality in blacks (HR: 1.66; 95% CI: 1.26, 2.19 and HR: 1.20; 95% CI: 1.12, 1.29, respectively), with diabetes mortality in Chinese (HR: 2.24; 95% CI: 1.68, 2.97), and with IHD mortality in whites (HR: 1.31; 95% CI: 1.02, 1.69) (all P-trend < 0.001). The choline-mortality association was modified by alcohol consumption and appeared stronger among individuals with existing cardiometabolic disease. Betaine intake was associated with increased cardiometabolic mortality in Chinese only (HR: 1.16; 95% CI: 1.08, 1.25; P-trend < 0.001). CONCLUSIONS: High choline intake was associated with increased cardiometabolic mortality in racially diverse populations.

2.
Blood Adv ; 4(1): 181-190, 2020 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-31935283

RESUMO

Persons of African ancestry (AA) have a twofold higher risk for multiple myeloma (MM) compared with persons of European ancestry (EA). Genome-wide association studies (GWASs) support a genetic contribution to MM etiology in individuals of EA. Little is known about genetic risk factors for MM in individuals of AA. We performed a meta-analysis of 2 GWASs of MM in 1813 cases and 8871 controls and conducted an admixture mapping scan to identify risk alleles. We fine-mapped the 23 known susceptibility loci to find markers that could better capture MM risk in individuals of AA and constructed a polygenic risk score (PRS) to assess the aggregated effect of known MM risk alleles. In GWAS meta-analysis, we identified 2 suggestive novel loci located at 9p24.3 and 9p13.1 at P < 1 × 10-6; however, no genome-wide significant association was noted. In admixture mapping, we observed a genome-wide significant inverse association between local AA at 2p24.1-23.1 and MM risk in AA individuals. Of the 23 known EA risk variants, 20 showed directional consistency, and 9 replicated at P < .05 in AA individuals. In 8 regions, we identified markers that better capture MM risk in persons with AA. AA individuals with a PRS in the top 10% had a 1.82-fold (95% confidence interval, 1.56-2.11) increased MM risk compared with those with average risk (25%-75%). The strongest functional association was between the risk allele for variant rs56219066 at 5q15 and lower ELL2 expression (P = 5.1 × 10-12). Our study shows that common genetic variation contributes to MM risk in individuals with AA.

4.
J Am Heart Assoc ; 8(24): e013404, 2019 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-31822218

RESUMO

Background Data are limited on use patterns of low-dose aspirin and its role for primary prevention of cardiovascular disease (CVD) in different racial and ethnic groups. Methods and Results Overall, 65 231 non-Hispanic black and white people aged 40 to 79 years with no history of CVD enrolled from 2002 through 2009 in the SCCS (Southern Community Cohort Study). At cohort entry, the simplified Framingham 10-year CVD risk was calculated, and data related to low-dose aspirin use and clinical and socioeconomic covariates were collected. Race- and ethnicity-specific adjusted odds ratios for characteristics of low-dose aspirin users and hazard ratios for ischemic cardiac death according to aspirin use were calculated using multivariate logistic and Cox regression models. Black participants were less likely to take low-dose aspirin compared with white participants, regardless of CVD risk and covariates (adjusted odds ratio: 0.79; 95% CI, 0.75-0.82). Over a median follow-up of 11.3 years, low-dose aspirin use was associated with a trend toward decreased risk of ischemic cardiac death in white participants (adjusted hazard ratio: 0.86; 95% CI, 0.68-1.10), especially in women (adjusted hazard ratio: 0.72; 95% CI, 0.51-1.02), but not in black participants (adjusted hazard ratio: 1.18; 95% CI, 0.98-1.40). Similar trends were observed when the analysis was restricted to high-risk individuals aged 50 to 69 or 50 to 59 years, ages for which guidelines consider aspirin for CVD primary prevention. Conclusions Low-dose aspirin use for primary prevention of CVD is lower among black than white patients. Its use might be associated with a disparate impact on ischemic cardiac death according to race and ethnicity. Although additional studies are required, these findings provide no evidence of a beneficial effect of aspirin among black patients for CVD primary prevention.

5.
JAMA Netw Open ; 2(12): e1917995, 2019 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-31860105

RESUMO

Importance: Colorectal cancer (CRC) screening is rarely studied in populations who may face additional barriers to participate in cancer screening, such as African American individuals and individuals with low socioeconomic status (SES). Objective: To examine the associations of CRC screening and modalities with CRC incidence and mortality by race and SES. Design, Setting, and Participants: This cohort study used data from the Southern Community Cohort Study, which enrolled more than 85 000 participants from community health centers or stratified random sampling of the general population in 12 states in the southeastern United States. The present study included data from cohort members who were eligible for CRC screening as recommended by expert organizations based on age and family history. Participants completed questionnaires from 2002 to 2009 and were contacted again from 2008 to 2012. Linkages to state cancer registries and the National Death Index as of December 31, 2016, identified incident CRC and vital status. Data analysis was performed from January 1, 2018, to October 30, 2019. Main Outcomes and Measures: Incident CRC (n = 632) and mortality (n = 10 003). Cox proportional hazards regression models evaluated associations between screening modalities and CRC risk and mortality. Information on fecal occult blood test use was only obtained on the follow-up questionnaire. Self-identified race was measured as African American/black, white, or other, and SES was defined by household income. Results: This study included 47 596 participants (median baseline age, 54 years [interquartile range, 10 years]; 32 185 [67.6%] African American; 28 884 [60.7%] female; and 26 075 [54.8%] with household income <$15 000). A total of 24 432 participants (63.9%) had never undergone CRC testing at baseline. The CRC testing assessed at baseline and follow-up interviews was associated with significant CRC risk reduction (hazard ratio [HR], 0.55; 95% CI, 0.44-0.70 for ever colonoscopy at baseline). Results were similar in analyses stratified by race (African American: HR, 0.65; 95% CI, 0.50-0.85; white: HR, 0.44; 95% CI, 0.27-0.70) and household income (<$15 000: HR, 0.63; 95% CI, 0.46-0.86, ≥$15 000: HR, 0.49; 95% CI, 0.35-0.69). Ever sigmoidoscopy at baseline was associated with CRC risk reduction (HR, 0.66; 95% CI, 0.51-0.87), and undergoing fecal occult blood test in the interval between baseline and follow-up interview was associated with CRC risk reduction (HR, 0.75; 95% CI, 0.57-0.98). Inverse associations were also observed between CRC mortality and receipt of colonoscopy (HR for women, 0.39; 95% CI, 0.21-0.73; HR for men, 0.69; 95% CI, 0.40-1.18) and sigmoidoscopy (HR for women, 0.37; 95% CI, 0.16-0.85; HR for men, 0.82; 95% CI, 0.46-1.47); however, the association did not extend to fecal occult blood test (HR for women, 1.02; 95% CI, 0.62-1.70; HR for men, 1.03; 95% CI, 0.55-1.93). Conclusions and Relevance: In this study, CRC test rates were low among African American individuals and those with low SES. The findings suggest that screening, particularly with colonoscopy, is significantly associated with reduced risk of CRC and mortality. The CRC disparities experienced by individuals with low SES and African American individuals may be lessened by improving access to and uptake of CRC screening.

7.
mSystems ; 4(6)2019 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-31771977

RESUMO

Increasing evidence indicates the significant racial difference in gut, vaginal, and skin microbiomes. However, little is known regarding the racial difference in the oral microbiome. In this study, deep sequencing of 16S rRNA genes was utilized to assess the oral microbiome in mouth rinse samples of 1,058 African-Americans (AAs) and 558 European-Americans (EAs) from the Southern Community Cohort Study. Generally, AAs had a higher species richness than EAs, with P = 5.28 × 10-14 (Wilcoxon rank sum test) for Faith's phylogenetic diversity index. A significant difference in overall microbiome composition was observed between AAs and EAs, with P = 5.94 × 10-4 (MiRKAT) for the weighted UniFrac distance matrix. We also found 32 bacterial taxa showing a significant differential abundance or prevalence between the two racial groups at a Bonferroni-corrected P < 0.05 in linear or logistic regression analyses. Generally, AAs showed a higher abundance of Bacteroidetes and a lower abundance of Actinobacteria and Firmicutes Interestingly, four periodontal pathogens, Porphyromonas gingivalis, Prevotella intermedia, Treponema denticola, and Filifactor alocis, were more prevalent among AAs than among EAs, with Bonferroni-corrected P values of 5.23 × 10-6, 4.47 × 10-6, 1.08 × 10-3, and 4.49 × 10-5, respectively. In addition, all of these 32 taxa were significantly correlated with the percentage of genetic African ancestry. These findings call for research to understand how the racial difference in oral microbiome influences the health disparity.IMPORTANCE In this systemic investigation of racial differences in the oral microbiome using a large data set, we disclosed the significant differences in the oral microbial richness/evenness, as well as in the overall microbial composition, between African-Americans and European-Americans. We also found multiple oral bacterial taxa, including several preidentified oral pathogens, showing a significant different abundance or prevalence between African-Americans and European-Americans. Furthermore, these taxa were consistently found to be associated with the percentage of genetic African ancestry. Our findings warrant further research to understand how the racial difference in the oral microbiome influences the health disparity.

8.
Helicobacter ; : e12671, 2019 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-31746104

RESUMO

PURPOSE: To feasibly analyze associations of Helicobacter pylori (H. pylori) with disease in large cohort studies, assays are needed to assess H. pylori prevalence in existing biospecimens. However, serology has traditionally been unable to distinguish active from past infection. We sought to determine the sensitivity of seropositivity to H. pylori proteins to detect active infection. METHODS: We measured antibody responses to 13 H. pylori proteins using multiplex serology in serum samples of a training (n = 78) and validation set (n = 49) collected concurrently from patients undergoing urea breath test (UBT). To determine sensitivity of seropositivity to H. pylori proteins for active infection, a cutoff was applied to achieve 90% specificity. Antibody levels were retested in a subset of participants (n = 16) 6 months after baseline. RESULTS: With a specificity of 91%, seropositivity to H. pylori proteins VacA, GroEl, HcpC, and HP1564 ascertained active infection from 100% to 75% sensitivity. Positivity to a combination of these proteins (≥2 out of the 4) resulted in specificity of 90% and sensitivity of 100%. The validation set replicated results from the training set. Among those participants with successful H. pylori eradication after baseline, antibody levels decreased significantly for VacA, HcpC, and HP1564 when assessed 6 months later. CONCLUSION: Utilizing the cutoffs for seropositivity established through comparison with UBT, seropositivity to ≥2 of the H. pylori proteins VacA, GroEl, HcpC, and HP1564 determines active H. pylori infection at high specificity and sensitivity and may approximate the prevalence of active H. pylori infection in large cohorts.

9.
Drug Metab Dispos ; 47(12): 1388-1396, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31578206

RESUMO

Menthol, which creates mint flavor and scent, is often added to tobacco in both menthol and nonmenthol cigarettes. A potent tobacco carcinogen, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), is extensively metabolized to its equally carcinogenic metabolite 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) as (R)- or (S)-NNAL enantiomers. NNAL is detoxified by UDP-glucuronosyltransferase (UGT) enzymes, with glucuronidation occurring on either NNAL's pyridine ring nitrogen (NNAL-N-Gluc) or the chiral alcohol [(R)- or (S)-NNAL-O-Gluc]. To characterize a potential effect by menthol on NNAL glucuronidation, in vitro menthol glucuronidation assays and menthol inhibition of NNAL-Gluc formation assays were performed. Additionally, NNAL and menthol glucuronides (MG) were measured in the urine of smokers (n = 100) from the Southern Community Cohort Study. UGTs 1A9, 1A10, 2A1, 2A2, 2A3, 2B4, 2B7, and 2B17 all exhibited glucuronidating activity against both l- and d-menthol. In human liver microsomes, both l- and d-menthol inhibited the formation of each NNAL-Gluc, with a stereospecific difference observed between the formation of (R)-NNAL-O-Gluc and (S)-NNAL-O-Gluc in the presence of d-menthol but not l-menthol. With the exception of three nonmenthol cigarette smokers, urinary MG was detected in all menthol and nonmenthol smokers, with l-MG comprising >98% of total urinary MG. Levels of urinary NNAL-N-Gluc were significantly (P < 0.05) lower among subjects with high levels of total urinary MG; no significant changes in free NNAL were observed. These data suggest that the presence of menthol could lead to increases in alternative, activating metabolic pathways of NNAL in tobacco target tissues, increasing the opportunity for NNAL to damage DNA and lead to the development of tobacco-related cancers. SIGNIFICANCE STATEMENT: High levels of the major menthol metabolite, menthol-glucuronide, was observed in the urine of smokers of either menthol or nonmenthol cigarettes. The fact that a significant inverse correlation was observed between the levels of urinary menthol-glucuronide and NNAL-N-glucuronide, a major detoxification metabolite of the tobacco carcinogen, NNK, suggests that menthol may inhibit clearance of this important tobacco carcinogen.

10.
J Oral Microbiol ; 11(1): 1650597, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31489128

RESUMO

Few studies have evaluated the relationship of oral microbiome with obesity. We investigated the oral microbiome among 647 obese and 969 non-obese individuals from the Southern Community Cohort Study, through 16S rRNA gene sequencing in mouth rinse samples. We first investigated 16 taxa in two probiotic genera, Bifidobacterium and Lactobacillus. Among them, eight showed nominal associations with obesity (P < 0.05). Especially, Bifidobacterium (odds ratio [OR] = 0.67, 95% confidence interval [CI]:0.54, 0.83) and Bifidobacterium longum (OR = 0.57, 95% CI: 0.45, 0.73) were significantly associated with decreased obesity prevalence with false-discovery rate (FDR)-corrected P of 0.01 and 5.41 × 10-4, respectively. Multiple other bacterial taxa were also significantly associated with obesity prevalence at FDR-corrected P < 0.05. Among them, five in Firmicutes and two respectively in Actinobacteria and Proteobacteria were significantly associated with increased obesity prevalence. Significant associations with decreased obesity prevalence were observed for two taxa respectively in Actinobacteria and Firmicutes. Most of these taxa were associated with body mass index at study enrollment and weight gain during adulthood. Also, most of these associations were observed in both European- and African-Americans. Our findings indicate that multiple oral bacterial taxa, including several probiotic taxa, were significantly associated with obesity.

11.
BMJ ; 366: l5016, 2019 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-31511230

RESUMO

OBJECTIVE: To assess the effects of Helicobacter pylori treatment, vitamin supplementation, and garlic supplementation in the prevention of gastric cancer. DESIGN: Blinded randomized placebo controlled trial. SETTING: Linqu County, Shandong province, China. PARTICIPANTS: 3365 residents of a high risk region for gastric cancer. 2258 participants seropositive for antibodies to H pylori were randomly assigned to H pylori treatment, vitamin supplementation, garlic supplementation, or their placebos in a 2×2×2 factorial design, and 1107 H pylori seronegative participants were randomly assigned to vitamin supplementation, garlic supplementation, or their placebos in a 2×2 factorial design. INTERVENTIONS: H pylori treatment with amoxicillin and omeprazole for two weeks; vitamin (C, E, and selenium) and garlic (extract and oil) supplementation for 7.3 years (1995-2003). MAIN OUTCOME MEASURES: Primary outcomes were cumulative incidence of gastric cancer identified through scheduled gastroscopies and active clinical follow-up through 2017, and deaths due to gastric cancer ascertained from death certificates and hospital records. Secondary outcomes were associations with other cause specific deaths, including cancers or cardiovascular disease. RESULTS: 151 incident cases of gastric cancer and 94 deaths from gastric cancer were identified during 1995-2017. A protective effect of H pylori treatment on gastric cancer incidence persisted 22 years post-intervention (odds ratio 0.48, 95% confidence interval 0.32 to 0.71). Incidence decreased significantly with vitamin supplementation but not with garlic supplementation (0.64, 0.46 to 0.91 and 0.81, 0.57 to 1.13, respectively). All three interventions showed significant reductions in gastric cancer mortality: fully adjusted hazard ratio for H pylori treatment was 0.62 (95% confidence interval 0.39 to 0.99), for vitamin supplementation was 0.48 (0.31 to 0.75), and for garlic supplementation was 0.66 (0.43 to 1.00). Effects of H pylori treatment on both gastric cancer incidence and mortality and of vitamin supplementation on gastric cancer mortality appeared early, but the effects of vitamin supplementation on gastric cancer incidence and of garlic supplementation only appeared later. No statistically significant associations were found between interventions and other cancers or cardiovascular disease. CONCLUSIONS: H pylori treatment for two weeks and vitamin or garlic supplementation for seven years were associated with a statistically significant reduced risk of death due to gastric cancer for more than 22 years. H pylori treatment and vitamin supplementation were also associated with a statistically significantly reduced incidence of gastric cancer. TRIAL REGISTRATION: ClinicalTrials.gov NCT00339768.


Assuntos
Infecções por Helicobacter/terapia , Lesões Pré-Cancerosas/terapia , Neoplasias Gástricas/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antiulcerosos/administração & dosagem , Biópsia , China/epidemiologia , Suplementos Nutricionais , Quimioterapia Combinada/métodos , Feminino , Seguimentos , Alho/química , Mucosa Gástrica/microbiologia , Mucosa Gástrica/patologia , Gastroscopia , Infecções por Helicobacter/microbiologia , Infecções por Helicobacter/patologia , Helicobacter pylori/isolamento & purificação , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Extratos Vegetais/administração & dosagem , Lesões Pré-Cancerosas/microbiologia , Lesões Pré-Cancerosas/patologia , Inibidores da Bomba de Prótons/administração & dosagem , Neoplasias Gástricas/patologia , Neoplasias Gástricas/prevenção & controle , Análise de Sobrevida , Taxa de Sobrevida , Fatores de Tempo , Resultado do Tratamento , Vitaminas/administração & dosagem
12.
N Engl J Med ; 381(12): 1114-1123, 2019 09 19.
Artigo em Inglês | MEDLINE | ID: mdl-31532959

RESUMO

BACKGROUND: Persons with low socioeconomic status and nonwhite persons in the United States have high rates of cardiovascular disease. The use of combination pills (also called "polypills") containing low doses of medications with proven benefits for the prevention of cardiovascular disease may be beneficial in such persons. However, few data are available regarding the use of polypill therapy in underserved communities in the United States, in which adherence to guideline-based care is generally low. METHODS: We conducted a randomized, controlled trial involving adults without cardiovascular disease. Participants were assigned to the polypill group or the usual-care group at a federally qualified community health center in Alabama. Components of the polypill were atorvastatin (at a dose of 10 mg), amlodipine (2.5 mg), losartan (25 mg), and hydrochlorothiazide (12.5 mg). The two primary outcomes were the changes from baseline in systolic blood pressure and low-density lipoprotein (LDL) cholesterol level at 12 months. RESULTS: The trial enrolled 303 adults, of whom 96% were black. Three quarters of the participants had an annual income below $15,000. The mean estimated 10-year cardiovascular risk was 12.7%, the baseline blood pressure was 140/83 mm Hg, and the baseline LDL cholesterol level was 113 mg per deciliter. The monthly cost of the polypill was $26. At 12 months, adherence to the polypill regimen, as assessed on the basis of pill counts, was 86%. The mean systolic blood pressure decreased by 9 mm Hg in the polypill group, as compared with 2 mm Hg in the usual-care group (difference, -7 mm Hg; 95% confidence interval [CI], -12 to -2; P = 0.003). The mean LDL cholesterol level decreased by 15 mg per deciliter in the polypill group, as compared with 4 mg per deciliter in the usual-care group (difference, -11 mg per deciliter; 95% CI, -18 to -5; P<0.001). CONCLUSIONS: A polypill-based strategy led to greater reductions in systolic blood pressure and LDL cholesterol level than were observed with usual care in a socioeconomically vulnerable minority population. (Funded by the American Heart Association Strategically Focused Prevention Research Network and the National Institutes of Health; ClinicalTrials.gov number, NCT02278471.).


Assuntos
Anti-Hipertensivos/administração & dosagem , Combinação de Medicamentos , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Hipercolesterolemia/tratamento farmacológico , Hipertensão/tratamento farmacológico , Área Carente de Assistência Médica , Adesão à Medicação/estatística & dados numéricos , Adulto , Alabama , Anlodipino/administração & dosagem , Atorvastatina/administração & dosagem , LDL-Colesterol/sangue , Centros Comunitários de Saúde , Feminino , Humanos , Hidroclorotiazida/administração & dosagem , Hipercolesterolemia/sangue , Hipercolesterolemia/complicações , Hipertensão/complicações , Losartan/administração & dosagem , Masculino , Pessoa de Meia-Idade
13.
BMJ Open ; 9(8): e030661, 2019 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-31471443

RESUMO

OBJECTIVE: To examine whether lifestyle factors, including sedentary time and physical activity, could independently contribute to risk of end-stage renal disease (ESRD). STUDY DESIGN: Case-cohort study. SETTING: South-eastern USA. PARTICIPANTS: The Southern Community Cohort Study recruited ~86 000 black and white participants from 2002 to 2009. We assembled a case cohort of 692 incident ESRD cases and a probability sample of 4113 participants. PREDICTORS: Sedentary time was calculated as hours/day from daily sitting activities. Physical activity was calculated as metabolic equivalent (MET)-hours/day from engagement in light, moderate and vigorous activities. OUTCOMES: Incident ESRD. RESULTS: At baseline, among the subcohort, mean (SD) age was 52 (8.6) years, and median (25th, 75th centile) estimated glomerular filtration rate (eGFR) was 102.8 (85.9-117.9) mL/min/1.73 m2. Medians (25th-75th centile) for sedentary time and physical activity were 8.0 (5.5-12.0) hours/day and 17.2 (8.7-31.9) MET-hours/day, respectively. Median follow-up was 9.4 years. We observed significant interactions between eGFR and both physical activity and sedentary behaviour (p<0.001). The partial effect plot of the association between physical activity and log relative hazard of ESRD suggests that ESRD risk decreases as physical activity increases when eGFR is 90 mL/min/1.73 m2. The inverse association is most pronounced at physical activity levels >27 MET-hours/day. High levels of sitting time were associated with increased ESRD risk only among those with reduced kidney function (eGFR ≤30 mL/min/1.73 m2); this association was attenuated after excluding the first 2 years of follow-up. CONCLUSIONS: In a population with a high prevalence of chronic kidney disease risk factors such as hypertension and diabetes, physical activity appears to be associated with reduced risk of ESRD among those with preserved kidney function. A positive association between sitting time and ESRD observed among those with advanced kidney disease is likely due to reverse causation.

14.
J Epidemiol Community Health ; 73(12): 1108-1115, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31563898

RESUMO

BACKGROUND: Cigarette smoking is a common risk factor for diseases and cancers. Oral microbiota is also associated with diseases and cancers. However, little is known about the impact of cigarette smoking on the oral microbiota, especially among ethnic minority populations. METHODS: We investigated cigarette smoking in relationship with the oral microbiota in a large population of predominately low-income and African-American participants. Mouth rinse samples were collected from 1616 participants within the Southern Community Cohort Study, including 592 current-smokers, 477 former-smokers and 547 never-smokers. Oral microbiota was profiled by 16S ribosomal RNA gene deep sequencing. RESULTS: Current-smokers showed a different overall microbial composition from former-smokers (p=6.62×10-7) and never-smokers (p=6.00×10-8). The two probiotic genera, Bifidobacterium and Lactobacillus, were enriched among current-smokers when compared with never-smokers, with Bonferroni-corrected p values (PBonferroni ) of 1.28×10-4 and 5.89×10-7, respectively. The phylum Actinobacteria was also enriched in current-smokers when compared with never-smokers, with a median relative abundance of 12.35% versus 9.36%, respectively, and with a PBonferroni =9.11×10-11. In contrast, the phylum Proteobacteria was depleted in current smokers (PBonferroni =5.57×10-13), with the relative abundance being almost three times that of never-smokers (7.22%) when compared with that of current-smokers (2.47%). Multiple taxa within these two phyla showed differences in abundance/prevalence between current-smokers and never-smokers at PBonferroni <0.05. The differences in the overall microbial composition and abundance/prevalence of most taxa were observed among both African-Americans and European-Americans. Meanwhile, such differences were not observed between former-smokers and never-smokers. CONCLUSION: Smoking has strong impacts on oral microbial community, which was recovered after smoking cessation.

15.
BMC Nephrol ; 20(1): 308, 2019 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-31390993

RESUMO

INTRODUCTION: The Southern Community Cohort Study is a prospective study of low socioeconomic status (SES) blacks and whites from the southeastern US, where the burden of end-stage renal disease (ESRD) and its risk factors are high. We tested whether the 2.4-fold elevated risk of ESRD we previously observed in blacks compared to whites was explained by differences in baseline kidney function. METHODS: We conducted a case-cohort study of incident ESRD cases (n = 737) with stored blood and a probability sampled subcohort (n = 4238) and calculated estimated glomerular filtration rate (eGFR) from serum creatinine. 86% of participants were enrolled from community health centers in medically underserved areas and 14% from the general population in 12 states in the southeastern United States. Incident ESRD after entry into the cohort was ascertained by linkage of the cohort with the US Renal Data System (USRDS). RESULTS: Median (25th, 75th percentile) eGFR at baseline was 63.3 (36.0, 98.2) ml/min/1.73m2 for ESRD cases and 103.2 (86.0, 117.9) for subcohort. Black ESRD cases had higher median (25th, 75th) eGFR [63.3 (35.9, 95.9)] compared to whites [59.1 (39.4, 99.2)]. In multivariable Cox models accounting for sampling weights, baseline eGFR was a strong predictor of ESRD risk, and an interaction with race was detected (P = 0.029). The higher ESRD risk among blacks relative to whites persisted (hazard ratio: 2.58; 95% confidence interval: 1.65, 4.03) after adjustment for eGFR. CONCLUSION: In this predominantly lower SES cohort, the racial disparity in ESRD risk is not explained by differences in baseline kidney function.

16.
BMJ Open ; 9(7): e028200, 2019 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-31289078

RESUMO

OBJECTIVE: This study aimed to evaluate the impacts of various forms of religious involvement, beyond individual socioeconomic status, lifestyle factors, emotional well-being and social support, on all-cause and cause-specific mortality in socioeconomic disadvantaged neighbourhoods. DESIGN: This is a prospective cohort study conducted from 2002 through 2015. SETTINGS: This study included underserved populations in the Southeastern USA. PARTICIPANTS: A total of nearly 85 000 participants, primarily low-income American adults, were enrolled. Eligible participants were aged 40-79 years at enrolment, spoke English and were not under treatment for cancer within the prior year. RESULTS: We found that those who attended religious service attendance >1/week had 8% reduction in all-cause death and 15% reduction in cancer death relative to those who never attended. This association was substantially attenuated by depression score, social support, and socioeconomic and lifestyle covariates, and further attenuated by other forms of religious involvement. This association with all-cause mortality was found being stronger among those with higher socioeconomic status or healthier lifestyle behaviours. CONCLUSION: Our results indicate that the association between religious services attendance >1/week and lower mortality was moderate but robust, and could be attenuated and modified by socioeconomic or lifestyle factors in this large prospective cohort study of underserved populations in the Southeastern USA.

17.
Int J Radiat Biol ; : 1-9, 2019 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-31290725

RESUMO

Purpose: The risk of mesothelioma, including cancers of the pleura and peritoneum, was examined within two large cohorts of workers monitored for exposure to ionizing radiation. Methods and materials: Mortality was assessed among 253,632 workers routinely monitored for external radiation, including 30,724 industrial radiographers (IR) at shipyards, 142,583 workers at nuclear power plants (NPP), and 83,441 IR who had not worked at an NPP or shipyard. Follow-up was from 1969 through 2011. Standardized mortality ratios (SMRs) and 95% confidence intervals (CIs) were computed; observed numbers of deaths from mesothelioma (including cancers of the pleura and peritoneum) and asbestosis were compared with numbers expected based on age-, sex-, and calendar year-specific national mortality rates. Job history and quantitative asbestos exposure data were unavailable, but work at a shipyard was taken as a surrogate for the likelihood of exposure. Cox proportional hazards models were used to estimate hazard ratios (HRs) for mesothelioma in relation to estimated cumulative radiation exposure to the lung. Results: The mean duration of follow-up was 25.3 years (max 42 years). The mean cumulative lung dose was 28.6 mGy (7.3% > 250 mGy). Nearly 20% of the workers had died by 2011. A total of 421 mesothelioma deaths were found (75% occurring after 1999) with increased SMRs among workers monitored in shipyards (SMR 9.97; 95% CI 8.50-11.63) and for NPP workers (SMR 5.55; 95% CI 4.88-6.29), but not for IR who had not worked in shipyards (SMR 1.15; 95% CI 0.53-2.19). Likewise, deaths from asbestosis (n = 189) were also increased for shipyard and NPP workers (SMR = 18.1 and 9.2, respectively), but not among workers who never worked at a shipyard or NPP (SMR = 0.70; n = 1). Radiation dose to the lung was not associated with a statistically meaningful dose-response trend for mesothelioma in the combined cohorts (HR at 100 mGy = 1.10; 95% CI 0.96-1.27; p = .18), nor was mesothelioma risk associated with radiation exposure among IR who had not worked in a shipyard and assumed minimally exposed to asbestos. Conclusions: An elevated rate of death from mesothelioma was observed in two radiation-exposed occupational groups with potential for asbestos exposure. The increased risk of death from asbestosis, combined with little evidence of a rising trend in mesothelioma mortality with increasing radiation exposure, suggests that the mesothelioma (and asbestosis) excess in these workers was due to asbestos exposure in shipyards and power plants and not to occupational low-dose radiation.

18.
Int J Cancer ; 2019 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-31276202

RESUMO

Cell-mediated immune suppression may play an important role in lung carcinogenesis. We investigated the associations for circulating levels of tryptophan, kynurenine, kynurenine:tryptophan ratio (KTR), quinolinic acid (QA) and neopterin as markers of immune regulation and inflammation with lung cancer risk in 5,364 smoking-matched case-control pairs from 20 prospective cohorts included in the international Lung Cancer Cohort Consortium. All biomarkers were quantified by mass spectrometry-based methods in serum/plasma samples collected on average 6 years before lung cancer diagnosis. Odds ratios (ORs) and 95% confidence intervals (CIs) for lung cancer associated with individual biomarkers were calculated using conditional logistic regression with adjustment for circulating cotinine. Compared to the lowest quintile, the highest quintiles of kynurenine, KTR, QA and neopterin were associated with a 20-30% higher risk, and tryptophan with a 15% lower risk of lung cancer (all ptrend < 0.05). The strongest associations were seen for current smokers, where the adjusted ORs (95% CIs) of lung cancer for the highest quintile of KTR, QA and neopterin were 1.42 (1.15-1.75), 1.42 (1.14-1.76) and 1.45 (1.13-1.86), respectively. A stronger association was also seen for KTR and QA with risk of lung squamous cell carcinoma followed by adenocarcinoma, and for lung cancer diagnosed within the first 2 years after blood draw. This study demonstrated that components of the tryptophan-kynurenine pathway with immunomodulatory effects are associated with risk of lung cancer overall, especially for current smokers. Further research is needed to evaluate the role of these biomarkers in lung carcinogenesis and progression.

19.
JAMA Oncol ; 2019 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-31246249

RESUMO

Importance: The United States Preventive Services Task Force (USPSTF) recommends low-dose computed tomography screening for lung cancer. However, USPSTF screening guidelines were derived from a study population including only 4% African American smokers, and racial differences in smoking patterns were not considered. Objective: To evaluate the diagnostic accuracy of USPSTF lung cancer screening eligibility criteria in a predominantly African American and low-income cohort. Design, Setting, and Participants: The Southern Community Cohort Study prospectively enrolled adults visiting community health centers across 12 southern US states from March 25, 2002, through September 24, 2009, and followed up for cancer incidence through December 31, 2014. Participants included African American and white current and former smokers aged 40 through 79 years. Statistical analysis was performed from May 11, 2016, to December 6, 2018. Exposures: Self-reported race, age, and smoking history. Cumulative exposure smoking histories encompassed most recent follow-up questionnaires. Main Outcomes and Measures: Incident lung cancer cases assessed for eligibility for lung cancer screening using USPSTF criteria. Results: Among 48 364 ever smokers, 32 463 (67%) were African American and 15 901 (33%) were white, with 1269 incident lung cancers identified. Among all 48 364 Southern Community Cohort Study participants, 5654 of 32 463 African American smokers (17%) were eligible for USPSTF screening compared with 4992 of 15 901 white smokers (31%) (P < .001). Among persons diagnosed with lung cancer, a significantly lower percentage of African American smokers (255 of 791; 32%) was eligible for screening compared with white smokers (270 of 478; 56%) (P < .001). The lower percentage of eligible lung cancer cases in African American smokers was primarily associated with fewer smoking pack-years among African American vs white smokers (median pack-years: 25.8 [interquartile range, 16.9-42.0] vs 48.0 [interquartile range, 30.2-70.5]; P < .001). Racial disparity was observed in the sensitivity and specificity of USPSTF guidelines between African American and white smokers for all ages. Lowering the smoking pack-year eligibility criteria to a minimum 20-pack-year history was associated with an increased percentage of screening eligibility of African American smokers and with equitable performance of sensitivity and specificity compared with white smokers across all ages (for a 55-year-old current African American smoker, sensitivity increased from 32.2% to 49.0% vs 56.5% for a 55-year-old white current smoker; specificity decreased from 83.0% to 71.6% vs 69.4%; P < .001). Conclusions and Relevance: Current USPSTF lung cancer screening guidelines may be too conservative for African American smokers. The findings suggest that race-specific adjustment of pack-year criteria in lung cancer screening guidelines would result in more equitable screening for African American smokers at high risk for lung cancer.

20.
Cancer Epidemiol Biomarkers Prev ; 28(8): 1345-1352, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31160346

RESUMO

BACKGROUND: Precision interventions using biological data may enhance smoking treatment, yet are understudied among smokers who are disproportionately burdened by smoking-related disease. METHODS: We surveyed smokers in the NCI-sponsored Southern Community Cohort Study, consisting primarily of African-American, low-income adults. Seven items assessed attitudes toward aspects of precision smoking treatment, from undergoing tests to acting on results. Items were dichotomized as favorable (5 = strongly agree/4 = agree) versus less favorable (1 = strongly disagree/2 = disagree/3 = neutral); a summary score reflecting generalized attitudes was also computed. Multivariable logistic regression tested independent associations of motivation (precontemplation, contemplation, and preparation) and confidence in quitting (low, medium, and high) with generalized attitudes, controlling for sociodemographic factors and nicotine dependence. RESULTS: More than 70% of respondents endorsed favorable generalized attitudes toward precision medicine, with individual item favorability ranging from 64% to 83%. Smokers holding favorable generalized attitudes reported higher income and education (P < 0.05). Predicted probabilities of favorable generalized attitudes ranged from 63% to 75% across motivation levels [contemplation vs. precontemplation: adjusted odds ratio (AOR) = 2.10, 95% confidence interval (CI), 1.36-3.25, P = 0.001; preparation vs. precontemplation: AOR = 1.83, 95% CI, 1.20-2.78, P = 0.005; contemplation vs. preparation: AOR = 1.15, 95% CI, 0.75-1.77, P = 0.52] and from 59% to 78% across confidence (medium vs. low: AOR = 1.91, 95% CI, 1.19-3.07, P = 0.007; high vs. low: AOR = 2.62, 95% CI, 1.68-4.10, P < 0.001; medium vs. high: AOR = 0.73, 95% CI, 0.48-1.11, P = 0.14). CONCLUSIONS: Among disproportionately burdened community smokers, most hold favorable attitudes toward precision smoking treatment. Individuals with lower motivation and confidence to quit may benefit from additional intervention to engage with precision smoking treatment. IMPACT: Predominantly favorable attitudes toward precision smoking treatment suggest promise for future research testing their effectiveness and implementation.

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