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BACKGROUND: After accounting for smoking history, lung cancer incidence is greater in African Americans than Whites. In the multiethnic cohort, total nicotine equivalents (TNE) are higher in African Americans than Whites at similar reported cigarettes per day. Greater toxicant uptake per cigarette may contribute to the greater lung cancer risk of African Americans. METHODS: In a nested case-control lung cancer study within the Southern Community Cohort, smoking-related biomarkers were measured in 259 cases and 503 controls (40% White; 56% African American). TNE, the trans-3-hydroxycotinine/cotinine ratio, 4-(methylnitrosamino)-1-3-(pyridyl)-1-butanol (NNAL), mercapturic acid metabolites of volatile organic compounds, phenanthrene metabolites, cadmium (Cd), and (Z)-7-(1R,2R,3R,5S)-3,5-dihydroxy-2-[(E,3S)-3-hydroxyoct-1-enyl]cyclopenyl]hept-5-enoic acid were quantified in urine. Unconditional logistic regression was used to estimate the ORs and 95% confidence intervals (CI) for each biomarker and lung cancer risk. RESULTS: TNE, NNAL, and Cd were higher in cases than controls (adjusted for age, race, sex, body mass index, and cigarettes per day). Among cases, these levels were higher in African Americans compared with Whites. After accounting for age, sex, body mass index, and pack-years, a one-SD increase in log-TNE (OR = 1.30; 95% CI, 1.10-1.54) and log-NNAL (OR = 1.27; 95% CI, 1.03-1.58 with TNE adjustment) was associated with lung cancer risk. In this study, in which NNAL concentration is relatively high, the association for log-TNE was attenuated after adjustment for log-NNAL. CONCLUSIONS: Smoking-related biomarkers provide additional information for lung cancer risk in smokers beyond smoking pack-years. IMPACT: Urinary NNAL, TNE, and Cd concentrations in current smokers, particularly African American smokers, may be useful for predicting lung cancer risk.
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Negro o Afroamericano , Neoplasias Pulmonares , Población Blanca , Humanos , Masculino , Neoplasias Pulmonares/orina , Neoplasias Pulmonares/etiología , Neoplasias Pulmonares/epidemiología , Femenino , Negro o Afroamericano/estadística & datos numéricos , Persona de Mediana Edad , Estudios de Casos y Controles , Población Blanca/estadística & datos numéricos , Anciano , Biomarcadores de Tumor/orina , Estudios de Cohortes , Factores de Riesgo , Biomarcadores/orina , Fumar Cigarrillos/orina , Fumar Cigarrillos/efectos adversos , Fumar Cigarrillos/etnología , BlancoRESUMEN
BACKGROUND: The feasibility of precision smoking treatment in socioeconomically disadvantaged communities has not been studied. METHODS: Participants in the Southern Community Cohort Study who smoked daily were invited to join a pilot randomized controlled trial of three smoking cessation interventions: guideline-based care (GBC), GBC plus nicotine metabolism-informed care (MIC), and GBC plus counseling guided by a polygenic risk score (PRS) for lung cancer. Feasibility was assessed by rates of study enrollment, engagement, and retention, targeting > 70% for each. Using logistic regression, we also assessed whether feasibility varied by age, sex, race, income, education, and attitudes toward precision smoking treatment. RESULTS: Of 92 eligible individuals (79.3% Black; 68.2% with household income < $15,000), 67 (72.8%; 95% CI 63.0-80.9%) enrolled and were randomized. Of these, 58 (86.6%; 95% CI 76.4-92.8%) engaged with the intervention, and of these engaged participants, 43 (74.1%; 95% CI 61.6-83.7%) were retained at 6-month follow-up. Conditional on enrollment, older age was associated with lower engagement (OR 0.83, 95% CI 0.73-0.95, p = 0.008). Conditional on engagement, retention was significantly lower in the PRS arm than in the GBC arm (OR 0.18, 95% CI 0.03-1.00, p = 0.050). No other selection effects were observed. CONCLUSIONS: Genetically informed precision smoking cessation interventions are feasible in socioeconomically disadvantaged communities, exhibiting high enrollment, engagement, and retention irrespective of race, sex, income, education, or attitudes toward precision smoking treatment. Future smoking cessation interventions in this population should take steps to engage older people and to sustain participation in interventions that include genetic risk counseling. TRIAL REGISTRATION: ClinicalTrials.gov No. NCT03521141, Registered 27 April 2018, https://www. CLINICALTRIALS: gov/study/NCT03521141.
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Fumar , Fumar Tabaco , Anciano , Humanos , Estudios de Cohortes , Estudios de Factibilidad , Proyectos Piloto , Fumar/epidemiología , Fumar/terapia , Masculino , FemeninoRESUMEN
IMPORTANCE: Epidemiologic evidence regarding the outcomes of dietary sodium intake on mortality remains limited for low-income individuals, particularly Black people. OBJECTIVE: To investigate the associations of excessive dietary sodium with all-cause and cause-specific mortality among predominantly low-income Black and White Americans. DESIGN, SETTING, AND PARTICIPANTS: This cohort study included participants aged 40 to 79 years from the Southern Community Cohort Study who were recruited at Community Health Centers in 12 southeastern states from 2002 to 2009. Analyses were conducted between March 2022 and June 2023. EXPOSURES: Dietary sodium intake was assessed using a validated food frequency questionnaire at baseline. MAIN OUTCOMES AND MEASURES: Multivariable-adjusted Cox regression was used to estimate hazard ratios (HRs) and 95% CIs for mortality outcomes (all-cause, cardiovascular disease [CVD], coronary heart disease [CHD], stroke, heart failure, cancer, and other) associated with sodium intake. Nonlinear associations and population-attributable risk (PAR) of the mortality burden associated with excess sodium were further assessed. RESULTS: Among the 64â¯329 participants, 46â¯185 (71.8%) were Black, 18â¯144 (28.2%) were White, and 39â¯155 (60.9%) were female. The mean (SD) age at study enrollment was 51.3 (8.6) years for Black participants and 53.3 (9.3) years for White counterparts. Mean (SD) dietary sodium intake was 4512 (2632) mg/d in Black individuals and 4041 (2227) mg/d in White individuals; 37â¯482 Black individuals (81.2%) and 14â¯431 White individuals (79.5%) exceeded the current dietary recommendations of 2300 mg/d. During a median (IQR) follow-up of 13.8 (11.3-15.8) years, 17â¯811 deaths were documented, including 5701 from CVD. After adjustment for potential confounders, in Black individuals, HRs per 1000-mg increase in daily sodium intake were 1.07 (95% CI, 1.03-1.10) and 1.08 (95% CI, 1.02-1.14) for deaths from total CVD and CHD, respectively; while in White individuals, the corresponding HRs were 1.08 (95% CI, 1.02-1.14) and 1.13 (95% CI, 1.03-1.23). No significant associations were found for cancer mortality. PAR estimates suggest that sodium intake above the recommended threshold may account for 10% of total CVD, 13% of CHD, and 30% of heart failure deaths in this low-income southern population. CONCLUSIONS AND RELEVANCE: In this cohort study of 64â¯329 low-income Americans, nearly 80% of study participants consumed sodium exceeding the current recommended daily amount, which was associated with 10% to 30% of CVD mortality. Public health programs targeted to reduce sodium intake among this underserved population may be beneficial.
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Enfermedades Cardiovasculares , Insuficiencia Cardíaca , Neoplasias , Sodio en la Dieta , Femenino , Humanos , Masculino , Población Negra , Causas de Muerte , Estudios de Cohortes , Sodio , Sodio en la Dieta/efectos adversos , Blanco , Estados Unidos , Negro o Afroamericano , Adulto , Persona de Mediana Edad , AncianoRESUMEN
BACKGROUND: A high body mass index (BMI, kg/m2) is associated with decreased risk of breast cancer before menopause, but increased risk after menopause. Exactly when this reversal occurs in relation to menopause is unclear. Locating that change point could provide insight into the role of adiposity in breast cancer etiology. METHODS: We examined the association between BMI and breast cancer risk in the Premenopausal Breast Cancer Collaborative Group, from age 45 up to breast cancer diagnosis, loss to follow-up, death, or age 55, whichever came first. Analyses included 609,880 women in 16 prospective studies, including 9956 who developed breast cancer before age 55. We fitted three BMI hazard ratio (HR) models over age-time: constant, linear, or nonlinear (via splines), applying piecewise exponential additive mixed models, with age as the primary time scale. We divided person-time into four strata: premenopause; postmenopause due to natural menopause; postmenopause because of interventional loss of ovarian function (bilateral oophorectomy (BO) or chemotherapy); postmenopause due to hysterectomy without BO. Sensitivity analyses included stratifying by BMI in young adulthood, or excluding women using menopausal hormone therapy. RESULTS: The constant BMI HR model provided the best fit for all four menopausal status groups. Under this model, the estimated association between a five-unit increment in BMI and breast cancer risk was HR=0.87 (95% CI: 0.85, 0.89) before menopause, HR=1.00 (95% CI: 0.96, 1.04) after natural menopause, HR=0.99 (95% CI: 0.93, 1.05) after interventional loss of ovarian function, and HR=0.88 (95% CI: 0.76, 1.02) after hysterectomy without BO. CONCLUSION: The BMI breast cancer HRs remained less than or near one during the 45-55 year age range indicating that the transition to a positive association between BMI and risk occurs after age 55.
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Neoplasias de la Mama , Menopausia , Adulto , Femenino , Humanos , Persona de Mediana Edad , Adulto Joven , Índice de Masa Corporal , Neoplasias de la Mama/epidemiología , Neoplasias de la Mama/etiología , Neoplasias de la Mama/diagnóstico , Premenopausia , Estudios Prospectivos , Factores de RiesgoRESUMEN
INTRODUCTION: Low socioeconomic status has been linked to increased mortality. However, the impacts of poverty, alone or combined with health behaviors, on mortality and life expectancy have not been adequately investigated. METHODS: Data from the Southern Community Cohort Study was used, including nearly 86,000 participants recruited during 2002-2009 across 12 US southeastern states. Analysis was conducted from February 2022 to January 2023. RESULTS: During a median follow-up of 12.1 years, 19,749 deaths were identified. A strong dose-response relationship was found between household incomes and mortality, with a 3.3-fold (95%CI=3.1-3.6) increased all-cause mortality observed for individuals in the lowest income group (<$15,000/year) compared with those in the highest group (≥$50,000/year). Within each income group, mortality monotonically increased with declining healthy lifestyle score. Risk was significantly lower among those in the lowest income but healthiest lifestyle group, compared to those with the highest income but unhealthiest lifestyle (HR=0.82, 95%CI=0.69-0.97). Poor White participants appeared to experience higher all-cause mortality than poor Black participants. Life expectancy was more than 10.0 years shorter for those in the lowest income group compared with those in the highest income group. CONCLUSIONS: Poverty is strongly associated with increased risk of death, but the risks could be modestly abated by a healthier lifestyle. These findings call for a comprehensive strategy for enhancing a healthy lifestyle and improving income equality to reduce death risks, particularly among those experiencing health disparities due to poverty.
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Mortalidad , Pobreza , Humanos , Masculino , Femenino , Pobreza/estadística & datos numéricos , Persona de Mediana Edad , Mortalidad/tendencias , Adulto , Anciano , Estudios de Cohortes , Esperanza de Vida , Estilo de Vida , Sudeste de Estados Unidos/epidemiología , Estados Unidos/epidemiología , Conductas Relacionadas con la Salud , Renta/estadística & datos numéricosRESUMEN
The impact of tobacco exposure on health varies by race and ethnicity and is closely tied to internal nicotine dose, a marker of carcinogen uptake. DNA methylation is strongly responsive to smoking status and may mediate health effects, but study of associations with internal dose is limited. We performed a blood leukocyte epigenome-wide association study (EWAS) of urinary total nicotine equivalents (TNEs; a measure of nicotine uptake) and DNA methylation measured using the MethylationEPIC v1.0 BeadChip (EPIC) in six racial and ethnic groups across three cohort studies. In the Multiethnic Cohort Study (discovery, n = 1994), TNEs were associated with differential methylation at 408 CpG sites across >250 genomic regions (p < 9 × 10-8). The top significant sites were annotated to AHRR, F2RL3, RARA, GPR15, PRSS23, and 2q37.1, all of which had decreasing methylation with increasing TNEs. We identified 45 novel CpG sites, of which 42 were unique to the EPIC array and eight annotated to genes not previously linked with smoking-related DNA methylation. The most significant signal in a novel gene was cg03748458 in MIR383;SGCZ. Fifty-one of the 408 discovery sites were validated in the Singapore Chinese Health Study (n = 340) and the Southern Community Cohort Study (n = 394) (Bonferroni corrected p < 1.23 × 10-4). Significant heterogeneity by race and ethnicity was detected for CpG sites in MYO1G and CYTH1. Furthermore, TNEs significantly mediated the association between cigarettes per day and DNA methylation at 15 sites (average 22.5%-44.3% proportion mediated). Our multiethnic study highlights the transethnic and ethnic-specific methylation associations with internal nicotine dose, a strong predictor of smoking-related morbidities.
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MicroARNs , Fumadores , Humanos , Nicotina , Epigénesis Genética/genética , Epigenoma , Estudios de Cohortes , Estudios Prospectivos , Estudio de Asociación del Genoma Completo , Metilación de ADN/genética , Islas de CpG/genética , Receptores de Péptidos/genética , Receptores Acoplados a Proteínas G/genéticaRESUMEN
BACKGROUND: Despite the various anticancer activities of tocopherols, little is known about tocopherols associated with lung cancer risk among low-income African Americans (AA) and European Americans (EA) who are disproportionately affected by the disease. METHODS: We conducted a nested case-control study that included 209 incident lung cancer cases and 406 matched controls within the Southern Community Cohort Study. Using biospecimens collected at cohort enrollment, plasma levels of α-, ß/γ-, δ-, and total-tocopherols were measured by high-performance liquid chromatography with photodiode array detection. Conditional logistic regression was used to estimate ORs and 95% confidence intervals (CI) for lung cancer risk after adjusting for potential confounders. Stratified analyses were also conducted. RESULTS: Plasma levels of total-tocopherols were inversely associated with lung cancer risk overall [OR (95% CI) for the highest vs. lowest tertile = 0.51 (0.30-0.90)]. The inverse association remained significant among EAs [0.20 (0.06-0.65)], men [0.43 (0.21-0.90)], current smokers [0.49 (0.26-0.93)], and cases diagnosed within 2 years of blood draw [0.36 (0.15-0.86)], though we did not find a significant risk reduction among AAs [0.75 (0.39-1.45)]. Notably, we found significant interactions between α-tocopherol and race after controlling the FDR to correct for multiple comparisons (Pinteraction = 0.02). CONCLUSIONS: Our results indicate that plasma total-tocopherols are inversely associated with lung cancer risk, but the association may differ across specific isomeric forms of tocopherols, race, or other individuals' characteristics. Further large-scale studies are warranted to confirm our findings. IMPACT: Recommendations on tocopherols for lung cancer prevention should take isomers, race, and smoking behaviors into consideration.
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Neoplasias Pulmonares , Tocoferoles , Masculino , Humanos , Estudios de Cohortes , Neoplasias Pulmonares/epidemiología , Neoplasias Pulmonares/etiología , Estudios de Casos y Controles , Modelos Logísticos , Factores de RiesgoRESUMEN
BACKGROUND: Expansion of genome-wide association studies across population groups is needed to improve our understanding of shared and unique genetic contributions to breast cancer. We performed association and replication studies guided by a priori linkage findings from African ancestry (AA) relative pairs. METHODS: We performed fixed-effect inverse-variance weighted meta-analysis under three significant AA breast cancer linkage peaks (3q26-27, 12q22-23, and 16q21-22) in 9241 AA cases and 10 193 AA controls. We examined associations with overall breast cancer as well as estrogen receptor (ER)-positive and negative subtypes (193,132 SNPs). We replicated associations in the African-ancestry Breast Cancer Genetic Consortium (AABCG). RESULTS: In AA women, we identified two associations on chr12q for overall breast cancer (rs1420647, OR = 1.15, p = 2.50×10-6; rs12322371, OR = 1.14, p = 3.15×10-6), and one for ER-negative breast cancer (rs77006600, OR = 1.67, p = 3.51×10-6). On chr3, we identified two associations with ER-negative disease (rs184090918, OR = 3.70, p = 1.23×10-5; rs76959804, OR = 3.57, p = 1.77×10-5) and on chr16q we identified an association with ER-negative disease (rs34147411, OR = 1.62, p = 8.82×10-6). In the replication study, the chr3 associations were significant and effect sizes were larger (rs184090918, OR: 6.66, 95% CI: 1.43, 31.01; rs76959804, OR: 5.24, 95% CI: 1.70, 16.16). CONCLUSION: The two chr3 SNPs are upstream to open chromatin ENSR00000710716, a regulatory feature that is actively regulated in mammary tissues, providing evidence that variants in this chr3 region may have a regulatory role in our target organ. Our study provides support for breast cancer variant discovery using prioritization based on linkage evidence.
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Población Negra , Neoplasias de la Mama , Predisposición Genética a la Enfermedad , Femenino , Humanos , Población Negra/genética , Neoplasias de la Mama/genética , Estudio de Asociación del Genoma Completo , Polimorfismo de Nucleótido SimpleRESUMEN
AIMS: To determine the relationship of diabetes with pancreatic cancer incidence among African American and Whites of similar socio-economic status. METHODS: Using the Southern Community Cohort Study, we conducted a follow-up during 2002-2015 of pancreatic cancer incidence of 73,378 mostly low-income participants aged 40-79 years; 15,913 reported diabetes at baseline. Multivariable Cox analysis controlling for sex, family history of pancreatic cancer, BMI, smoking status, alcohol consumption, education, income and other important covariates, and with age as the timescale was used. RESULTS: Totally, 265 incident pancreatic cancer cases were observed. Pancreatic cancer risk was increased among those with diabetes (HR 1.54, CI 1.16-2.05), with similar increases among African Americans (HR 1.51, CI 1.08-2.11) and Whites (HR 1.78, CI 1.00-3.16). No trend in risk was observed for diabetes duration among those with diabetes, with HRs of 1.39 (0.91-2.11), 2.31 (1.51-3.54) and 1.23 (0.80-1.89) for <5, 5-9 and 10+ years duration, respectively. African Americans were at increased risk of pancreatic cancer (HR = 1.40, 95% CI 1.05-1.87), which persisted after adjusting for diabetes (HR 1.36, CI 1.02-1.81). The effect sizes for other pancreatic cancer risk factors with pancreatic cancer were similar by diabetes status, although a stronger association with low BMI was evident among those with diabetes. CONCLUSIONS: Diabetes increases pancreatic cancer risk similarly among African Americans and Whites in this Southern U.S.
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Diabetes Mellitus , Neoplasias Pancreáticas , Humanos , Estudios de Cohortes , Diabetes Mellitus/epidemiología , Factores de Riesgo , Neoplasias Pancreáticas/epidemiología , Incidencia , BlancoRESUMEN
We conducted a multi-ancestry genome-wide association study of prostate-specific antigen (PSA) levels in 296,754 men (211,342 European ancestry; 58,236 African ancestry; 23,546 Hispanic/Latino; 3,630 Asian ancestry; 96.5% of participants were from the Million Veteran Program). We identified 318 independent genome-wide significant (p≤5e-8) variants, 184 of which were novel. Most demonstrated evidence of replication in an independent cohort (n=95,768). Meta-analyzing discovery and replication (n=392,522) identified 447 variants, of which a further 111 were novel. Out-of-sample variance in PSA explained by our new polygenic risk score reached 16.9% (95% CI=16.1%-17.8%) in European ancestry, 9.5% (95% CI=7.0%-12.2%) in African ancestry, 18.6% (95% CI=15.8%-21.4%) in Hispanic/Latino, and 15.3% (95% CI=12.7%-18.1%) in Asian ancestry, and lower for higher age. Our study highlights how including proportionally more participants from underrepresented populations improves genetic prediction of PSA levels, with potential to personalize prostate cancer screening.
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BACKGROUND: Although tobacco smoking is the leading cause of lung cancer, interest in the relationship of diet quality on risk has been growing. METHODS: We examined the association between Healthy Eating Index-2010 (HEI-10) at enrollment and lung cancer incidence among 70,802 participants in a predominantly African American and low-income prospective cohort in the southern United States. Outcomes were ascertained through linkages with state cancer registries and the National Death Index (NDI). Hazard ratios by HEI-10 quartiles were assessed using Cox proportional hazard models adjusted for potential confounders. RESULTS: During ≤16 years of follow-up, 1454 incident lung cancers were identified. The lowest HEI-10 quartile compared to the highest was adversely associated with lung cancer risk (HR: 1.89, 95% CI 1.16-3.07) among male former smokers and female never smokers (HR: 2.58, 95% CI 1.06-6.28). CONCLUSIONS: Low-quality diet was associated with increased lung cancer risk among male former smokers and female never smokers but cautious interpretation of the findings should be taken due to the small number of lung cancers among never smokers and the possibility of residual confounding by smoking in ever smokers.
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Dieta , Neoplasias Pulmonares , Humanos , Masculino , Estados Unidos/epidemiología , Femenino , Factores de Riesgo , Estudios Prospectivos , Incidencia , Dieta/efectos adversos , Pobreza , Neoplasias Pulmonares/epidemiología , Neoplasias Pulmonares/etiología , Modelos de Riesgos ProporcionalesRESUMEN
Genome-wide polygenic risk scores (GW-PRSs) have been reported to have better predictive ability than PRSs based on genome-wide significance thresholds across numerous traits. We compared the predictive ability of several GW-PRS approaches to a recently developed PRS of 269 established prostate cancer-risk variants from multi-ancestry GWASs and fine-mapping studies (PRS269). GW-PRS models were trained with a large and diverse prostate cancer GWAS of 107,247 cases and 127,006 controls that we previously used to develop the multi-ancestry PRS269. Resulting models were independently tested in 1,586 cases and 1,047 controls of African ancestry from the California Uganda Study and 8,046 cases and 191,825 controls of European ancestry from the UK Biobank and further validated in 13,643 cases and 210,214 controls of European ancestry and 6,353 cases and 53,362 controls of African ancestry from the Million Veteran Program. In the testing data, the best performing GW-PRS approach had AUCs of 0.656 (95% CI = 0.635-0.677) in African and 0.844 (95% CI = 0.840-0.848) in European ancestry men and corresponding prostate cancer ORs of 1.83 (95% CI = 1.67-2.00) and 2.19 (95% CI = 2.14-2.25), respectively, for each SD unit increase in the GW-PRS. Compared to the GW-PRS, in African and European ancestry men, the PRS269 had larger or similar AUCs (AUC = 0.679, 95% CI = 0.659-0.700 and AUC = 0.845, 95% CI = 0.841-0.849, respectively) and comparable prostate cancer ORs (OR = 2.05, 95% CI = 1.87-2.26 and OR = 2.21, 95% CI = 2.16-2.26, respectively). Findings were similar in the validation studies. This investigation suggests that current GW-PRS approaches may not improve the ability to predict prostate cancer risk compared to the PRS269 developed from multi-ancestry GWASs and fine-mapping.
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Predisposición Genética a la Enfermedad , Neoplasias de la Próstata , Humanos , Masculino , Población Negra/genética , Estudio de Asociación del Genoma Completo , Herencia Multifactorial/genética , Neoplasias de la Próstata/genética , Factores de Riesgo , Población Blanca/genéticaRESUMEN
Genome-wide polygenic risk scores (GW-PRS) have been reported to have better predictive ability than PRS based on genome-wide significance thresholds across numerous traits. We compared the predictive ability of several GW-PRS approaches to a recently developed PRS of 269 established prostate cancer risk variants from multi-ancestry GWAS and fine-mapping studies (PRS 269 ). GW-PRS models were trained using a large and diverse prostate cancer GWAS of 107,247 cases and 127,006 controls used to develop the multi-ancestry PRS 269 . Resulting models were independently tested in 1,586 cases and 1,047 controls of African ancestry from the California/Uganda Study and 8,046 cases and 191,825 controls of European ancestry from the UK Biobank and further validated in 13,643 cases and 210,214 controls of European ancestry and 6,353 cases and 53,362 controls of African ancestry from the Million Veteran Program. In the testing data, the best performing GW-PRS approach had AUCs of 0.656 (95% CI=0.635-0.677) in African and 0.844 (95% CI=0.840-0.848) in European ancestry men and corresponding prostate cancer OR of 1.83 (95% CI=1.67-2.00) and 2.19 (95% CI=2.14-2.25), respectively, for each SD unit increase in the GW-PRS. However, compared to the GW-PRS, in African and European ancestry men, the PRS 269 had larger or similar AUCs (AUC=0.679, 95% CI=0.659-0.700 and AUC=0.845, 95% CI=0.841-0.849, respectively) and comparable prostate cancer OR (OR=2.05, 95% CI=1.87-2.26 and OR=2.21, 95% CI=2.16-2.26, respectively). Findings were similar in the validation data. This investigation suggests that current GW-PRS approaches may not improve the ability to predict prostate cancer risk compared to the multi-ancestry PRS 269 constructed with fine-mapping.
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BACKGROUND: Previous studies on calcium intake and lung cancer risk reported inconsistent associations, possibly due to the differences in intake amounts and contributing sources of calcium and smoking prevalence. OBJECTIVES: We investigated the associations of lung cancer risk with intake of calcium from foods and/or supplements and major calcium-rich foods in 12 studies. METHODS: Data from 12 prospective cohort studies conducted in the United States, Europe, and Asia were pooled and harmonized. We applied the DRI to categorize calcium intake based on the recommendations and quintile distribution to categorize calcium-rich food intake. We ran multivariable Cox regression by each cohort and pooled risk estimates to compute overall HR (95% CI). RESULTS: Among 1,624,244 adult men and women, 21,513 incident lung cancer cases were ascertained during a mean follow-up of 9.9 y. Overall, the dietary calcium intake was not significantly associated with lung cancer risk; the HRs (95% CI) were 1.08 (0.98-1.18) for higher (>1.5 RDA) and 1.01 (0.95-1.07) for lower intake (<0.5 RDA) comparing with recommended intake (EAR to RDA). Milk and soy food intake were positively or inversely associated with lung cancer risk [HR (95% CI) = 1.07 (1.02-1.12) and 0.92 (0.84-1.00)], respectively. The positive association with milk intake was significant only in European and North American studies (P-interaction for region = 0.04). No significant association was observed for calcium supplements. CONCLUSIONS: In this largest prospective investigation, overall, calcium intake was not associated with risk of lung cancer, but milk intake was associated with a higher risk. Our findings underscore the importance of considering food sources of calcium in studies of calcium intake.
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Calcio , Neoplasias Pulmonares , Masculino , Adulto , Humanos , Femenino , Estados Unidos/epidemiología , Animales , Estudios Prospectivos , Factores de Riesgo , Leche , Neoplasias Pulmonares/epidemiología , Neoplasias Pulmonares/etiología , Calcio de la Dieta , Productos LácteosRESUMEN
BACKGROUND: Vitamin D deficiency is more common among African-ancestry individuals and may be associated with adverse health outcomes. Vitamin D binding protein (VDBP) regulates concentrations of biologically active vitamin D. OBJECTIVE: We conducted genome-wide association study (GWAS) of VDBP and 25-hydroxyvitamin D among African-ancestry individuals. METHODS: Data were collected from 2,602 African American adults from the Southern Community Cohort Study (SCCS) and 6,934 African- or Caribbean-ancestry adults from the UK Biobank. Serum VDBP concentrations were available only in the SCCS and were measured by using the Polyclonal Human VDBP ELISA kit. Serum 25-hydroxyvitamin D concentrations for both study samples were measured by using Diasorin Liason, a chemiluminescent immunoassay. Participants were genotyped for single nucleotide polymorphisms (SNPs) with genome-wide coverage by using Illumina or Affymetrix platforms. Fine-mapping analysis was performed by using forward stepwise linear regression models including all variants with P value < 5 × 10-8 and within 250 kbps of a lead SNP. RESULTS: We identified 4 loci notably associated with VDBP concentrations in the SCCS population: rs7041 (per allele ß = 0.61 µg/mL, SE = 0.05, P = 1.4 × 10-48) and rs842998 (per allele ß = 0.39 µg/mL, SE = 0.03, P = 4.0 × 10-31) in GC, rs8427873 (per allele ß = 0.31 µg/mL, SE = 0.04, P = 3.0 × 10-14) near GC and rs11731496 (per allele ß = 0.21 µg/mL, SE = 0.03, P = 3.6 × 10-11) in between GC and NPFFR2. In conditional analyses, which included the above-mentioned SNPs, only rs7041 remained notable (P = 4.1 × 10-21). SNP rs4588 in GC was the only GWAS-identified SNP associated with 25-hydroxyvitamin D concentration. Among UK Biobank participants: per allele ß = -0.11 µg/mL, SE = 0.01, P = 1.5 × 10-13; in the SCCS: per allele ß = -0.12 µg/mL, SE = 0.06, P = 2.8 × 10-02). rs7041 and rs4588 are functional SNPs that influence the binding affinity of VDBP to 25-hydroxyvitamin D. CONCLUSIONS: Our results were in line with previous studies conducted in European-ancestry populations, showing that GC, the gene that directly encodes for VDBP, would be important for VDBP and 25-hydroxyvitamin D concentrations. The current study extends our knowledge of the genetics of vitamin D in diverse populations.
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Estudio de Asociación del Genoma Completo , Deficiencia de Vitamina D , Adulto , Humanos , Estudios de Cohortes , Vitamina D , Deficiencia de Vitamina D/genética , Vitaminas , Calcifediol , Proteína de Unión a Vitamina D/genética , Polimorfismo de Nucleótido SimpleRESUMEN
PURPOSE: Physical activity (PA) is associated with many health benefits. While PA has been associated with reduced mortality after breast cancer diagnosis in many studies, few studies have examined the role of PA in breast cancer survival among underserved and minority populations, including Black women. We investigated PA in association with mortality among Black predominantly low-income breast cancer survivors in the Southern Community Cohort Study (SCCS). METHODS: Study participants were women diagnosed with incident breast cancer (n = 949) in the SCCS, which is a prospective cohort study of predominantly low-income adults aged 40-79 years recruited from 12 Southeastern states between 2002 and 2009. Participants completed a detailed baseline questionnaire, with annual follow-up for mortality via registry linkages. Cox regression models were used to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for associations of pre-diagnosis PA (measured via a validated questionnaire) with all-cause and breast cancer-specific mortality. RESULTS: Breast cancer survivors had a mean age of 61.1 years and most (79.3%) had a household income of < $25,000. In adjusted models, higher levels of total PA (MET-hours/day) were inversely associated with all-cause mortality with HRs (95% CIs): 0.79 (0.59-1.06), 0.66 (0.49-0.90), and 0.60 (0.43-0.84), for Q2, Q3, and Q4 (reference: Q1), respectively, ptrend ≤ 0.01. A similar inverse association was found for breast cancer-specific mortality. CONCLUSION: Higher levels of pre-diagnosis PA were associated with improved survival among low-income Black breast cancer survivors. Resources to reduce barriers to PA participation and increase support for education and intervention efforts to promote PA among Black women are needed.
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Neoplasias de la Mama , Adulto , Humanos , Femenino , Persona de Mediana Edad , Masculino , Estudios de Cohortes , Estudios Prospectivos , Neoplasias de la Mama/diagnóstico , Ejercicio Físico , Encuestas y CuestionariosRESUMEN
To investigate how differences in income and education levels may contribute to disparities in incidence of Alzheimer's disease and related dementia (ADRD), we compared ADRD incidence in traditional Medicare claims for 11,132 Black and 7703 White participants aged 65 and over from a predominantly low-income cohort. We examined whether the relationship between ADRD incidence and race varied by income or education. Based on 2015 incident ADRD diagnoses, Black and White participants had unadjusted incidence rates of 26.5 and 23.2 cases per 1000 person-years, respectively (rate ratio 1.14, 95% CI 1.05-1.25). In multivariable Cox proportional hazard models, the relationship between race and incident ADRD diagnosis did not vary by education level (p-interaction = 0.748) but was modified by income level (p-interaction = 0.007), with higher ADRD incidence among Black participants observed only among higher income groups. These results highlight the importance of understanding how race and economic factors influence ADRD incidence and diagnosis rates.
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Enfermedad de Alzheimer , Estados Unidos/epidemiología , Anciano , Humanos , Enfermedad de Alzheimer/diagnóstico , Enfermedad de Alzheimer/epidemiología , Blanco , Medicare , Renta , PobrezaRESUMEN
Higher 25-hydroxyvitamin D is associated with lower colorectal cancer (CRC) risk, with limited data from African Americans (AAs), who have greater risk for CRC and 25-hydroxyvitamin D deficiency. In a predominantly AA sample of CRC cases from the Southern Community Cohort Study (SCCS), we report associations between vitamin D biomarkers and tumor expression of proteins implicated in vitamin D's anti-tumorigenic pathways (e.g. proliferation and inflammation) and CRC prognosis. SCCS participants with incident CRC were identified via state cancer registries. Serum 25-hydroxyvitamin D and vitamin D binding protein (VDBP) were measured at enrollment. 'Free' 25-hydroxyvitamin D was calculated via standard equation. Cellular Ki67, p53, and COX-2 were measured from tumor samples and categorized using literature-defined cut-points related to survival. Generalized linear models were used to measure associations between vitamin D exposures, tumor biomarkers, and stage. In total, 104 cases (40-79 years) were analyzed. 25-hydroxyvitamin D was not associated with high Ki67 (odds ratio (OR) per 1-standard deviation (SD) increase [95% confidence interval] 1.35[0.86-2.11]), p53 (0.75[0.47-1.20]), or COX-2 expression (1.25[0.78-2.01]), or metastatic disease (1.04[0.59-1.81]). Mean biomarker expression was unrelated to 25-hydroxyvitamin D (p-trend ≥.09). Null associations were observed for VDBP and free 25-hydroxyvitamin D. In AAs (n = 70), higher VDBP was associated with lower odds of high Ki67 expression (0.53[0.28-0.98], p-trend =.04). In conclusion, we observed no associations between 25-hydroxyvitamin D and prognostic marker expression in CRC. An inverse association between VDBP and tumor Ki67 in AAs is consistent with reports showing relationships with reduced CRC mortality.
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Neoplasias Colorrectales , Proteína p53 Supresora de Tumor , Humanos , Ciclooxigenasa 2/genética , Estudios de Cohortes , Antígeno Ki-67/genética , Proteína de Unión a Vitamina D , Calcifediol , Vitaminas , BiomarcadoresRESUMEN
INTRODUCTION: Mutations of the TP53 gene lead to the production of autoantibodies against p53, a major tumor suppressor protein. Although studies have indicated the association of p53 autoantibodies with human cancers, epidemiologic evidence on lung cancer is still lacking. METHODS: In this nested case-control study conducted within the Southern Community Cohort Study, we investigated the association of circulating p53 autoantibodies with the subsequent risk of developing lung cancer. Using blood samples collected prior to any cancer diagnosis from 295 cases and their individually matched controls, seroreactivity to p53 was assessed by fluorescent bead-based multiplex serology. Conditional logistic regression models were used to estimate odds ratios (OR) and 95 % confidence intervals (CI) for lung cancer risk associated with p53 autoantibodies. RESULTS: After adjustment for potential confounders, p53 seropositivity was significantly associated with an increased risk of lung cancer (OR=2.98, 95 % CI: 1.10-8.06) among African Americans, but not among European Americans (OR=1.21, 95 % CI: 0.24-6.15). The positive associations were restricted to men (OR=4.59, 95 % CI: 1.30-16.16) and participants with a short interval (≤ 4 years) from blood collection to diagnosis (OR=4.30, 95 % CI: 1.33-13.89). CONCLUSION: Our findings add to the evidence supporting p53 autoantibodies as a biomarker of lung cancer.
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Observational studies found inverse associations of dietary carotenoids and vitamin A intakes with lung cancer risk. However, interventional trials among high-risk individuals showed that ß-carotene supplements increased lung cancer risk. Most of the previous studies were conducted among European descendants or Asians. We prospectively examined the associations of lung cancer risk with dietary intakes of carotenoids and vitamin A in the Southern Community Cohort Study, including 65,550 participants with 1204 incident lung cancer cases. Multivariate Cox regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Lung cancer cases had lower energy-adjusted dietary intakes of all carotenoids and vitamin A than non-cases. However, dietary intakes of carotenoids and vitamin A were not associated with overall lung cancer risk. A significant positive association of dietary vitamin A intake with lung cancer risk was observed among current smokers (HRQ4 vs. Q1 = 1.23; 95% CI: 1.02-1.49; Ptrend = 0.01). In addition, vitamin A intake was associated with an increased risk of adenocarcinoma among African Americans (HRQ4 vs. Q1 = 1.55; 95%CI: 1.08-2.21; Ptrend = 0.03). Dietary lycopene intake was associated with an increased risk of lung cancer among former smokers (HRQ4 vs. Q1 = 1.50; 95% CI: 1.04-2.17; Ptrend = 0.03). There are positive associations of dietary ß-cryptoxanthin intake with squamous carcinoma risk (HRQ4 vs. Q1 = 1.49; 95% CI: 1.03-2.15; Ptrend = 0.03). Further studies are warranted to confirm our findings.