Supplementary Table S1: Characteristics of participants by mortality status

Supplementary Table S3: Power analyses for Cox-proportional hazards models concerning the associations between serum 25-hydroxyvitamin D and mortality outcomes, with adjustment for mortality risk factors

Supplementary Table S2: Median [IQR] time between SCCS enrollment and cancer incidence, end of follow-up in 218 colorectal cancer patients

METHODS:Investigated the association of multiple cardiometabolic comorbidities with total/major cause-specific mortality and evaluate if this association might be modified by race among predominantly low-income Black and White participants. METHODS:The Southern Community Cohort Study, prospective cohort study. Participants (40-79 years) recruited predominantly from community health centers across 12 states in southeastern United States. Enrollment began in 2002 and concluded in 2009, follow-up until 2020. Cardiometabolic comorbidities (diabetes, hypertension, myocardial infarction, stroke) ascertained at the baseline survey. Cox proportional hazard models used. RESULTS:Study included 76,721 participants; 16,197, 41,944, 5,247, and 4,919 participants with prior diagnosis of diabetes, hypertension, myocardial infarction, and stroke, respectively at baseline. Compared to individuals with no comorbidity, individuals with any single comorbidity experienced a significantly 30 to 90% increased rate of death due to any causes. The increase in mortality was elevated with an increasing number of comorbidities, with HR of 3.81 (95% CI: 3.26-4.46) and a cumulative risk of 62.5% at age 75 years for total mortality for those with four comorbidities. The risk was high for death due to cardiovascular diseases (HR: 6.18, 95% CI: 5.12-7.47). These associations were stronger among Blacks than Whites. Individuals with four comorbidities at age 40 years were estimated to have a 16-year loss in life expectancy compared with those without any comorbidity. CONCLUSION:Cardiometabolic comorbidities were associated with increases in all-cause and major cause-specific mortality, particularly Black Americans. This study calls for effective measures to prevent cardiometabolic comorbidities to reduce premature deaths in underserved Americans.

BACKGROUND:We investigated associations between diabetes and mortality among participants with incident colorectal cancer (CRC) from the Southern Community Cohort Study. METHODS:Participants (73% non-Hispanic Black; 60% income < $15,000) were recruited between 2002-2009. Diabetes was self-reported at enrollment and follow-up surveys at approximately 5-year intervals. Incident CRC and mortality were identified via state registries and the National Death Index. Proportional hazards models calculated associations between diabetes with overall, CRC-specific mortality among 1059 participants with incident CRC. RESULTS:Diabetes prior to diagnosis is associated with elevated overall (hazard ratio [95% confidence interval]: (1.46[1.22-1.75]), and CRC-specific mortality (1.36[1.06-1.74])) after adjustment for tumor stage. For non-Hispanic Black and non-Hispanic White participants, consistent associations were observed for overall (1.35[1.10-1.66] vs. 1.89[1.31-2.72], respectively, p-interaction = 0.11) and CRC-specific mortality (1.30[0.99-1.71] vs. 1.77[1.06-2.95], respectively, p-interaction = 0.28). For individuals with incomes <$15,000/year, associations with overall (1.44[1.15-1.79]) and CRC-specific mortality (1.28[0.94-1.73]) were similar to the full sample. Associations with overall (1.71[1.37-2.13]) and CRC-specific mortality (1.65[1.22-2.22]) were highest for diabetes ≥ 10 years at diagnosis. CONCLUSIONS:Pre-diagnosis diabetes is associated with higher mortality among participants with incident CRC from a predominantly non-Hispanic Black cohort with lower socioeconomic status. The higher prevalence of diabetes in this population may contribute to racial disparities in CRC mortality.

Background We characterized age at diagnosis and estimated sex differences for lung cancer and its histological subtypes among individuals who never smoke. Methods We analyzed the distribution of age at lung cancer diagnosis in 33,793 individuals across 8 cohort studies and two national registries from East Asia, the United States (US) and the United Kingdom (UK). Student’s t-tests were used to assess the study population differences (Δ years) in age at diagnosis comparing females and males who never smoke across subgroups defined by race/ethnicity, geographic location, and histological subtypes. Results We found that among Chinese individuals diagnosed with lung cancer who never smoke, females were diagnosed with lung cancer younger than males in the Taiwan Cancer Registry ( n = 29,832) (Δ years = −2.2 (95% confidence interval (CI):−2.5, −1.9), in Shanghai ( n = 1049) (Δ years = −1.6 (95% CI:-2.9, −0.3), and in Sutter Health and Kaiser Permanente Hawaiʽi in the US ( n = 82) (Δ years = −11.3 (95% CI: −17.7, −4.9). While there was a suggestion of similar patterns in African American and non-Hispanic White individuals. the estimated differences were not consistent across studies and were not statistically significant. Conclusions We found evidence of sex differences for age at lung cancer diagnosis among individuals who never smoke.

INTRODUCTION:Physical inactivity and sedentary behavior are recognized as independent risk factors for many diseases. However, studies investigating their associations with total and cause-specific mortality in low-income and Black populations are limited, particularly among older adults. METHODS:A prospective cohort study was conducted among 8,337 predominantly low-income and Black Americans aged ≥65 years residing in the southern United States. Participants reported their daily sitting time and leisure-time physical activity (LTPA) at baseline (2002-2009), and mortality data were collected through 2019. Analysis was conducted from September 2022 to October 2023. RESULTS:During a median follow-up of 12.25 years, nearly 50% (n=4,111) were deceased. A prolonged sitting time (>10 hours/day versus <4 hours/day) was associated with elevated all-cause mortality (hazard ratios [HR], 1.15; 95% confidence intervals [CI], 1.04-1.27) after adjusting for LTPA and other potential confounders. LTPA was associated with a reduced risk of all-cause mortality, with an adjusted HR of 0.75 (95% CI 0.64, 0.88) associated with 150-300 minutes per week of moderate-intensity physical activity. Individuals who were physically inactive and had a sitting time of >10 hours/day had the highest mortality risk (HR, 1.48; 95% CI, 1.23-1.78), compared with those who were physically active and had low sitting time. These associations were more pronounced for mortality due to cardiovascular diseases. CONCLUSIONS:High sitting time is an independent risk factor for all-cause and cardiovascular disease mortality, and LTPA could partially attenuate the adverse association of prolonged sitting time with mortality.

Background: No prospective observational study has specifically examined the associations between dietary intakes of medium-chain fatty acids and risk of colorectal cancer. Objectives: This study examined the association between dietary intakes of medium-chain fatty acids and colorectal cancer risk overall and by racial subgroups in a predominantly low-income United States population. Methods: This prospective study included 71,599 eligible participants aged 40 to 79 who were enrolled in the Southern Community Cohort Study between 2002 and 2009 in 12 southeastern United States states. Incident colorectal cancer cases were ascertained via linkage to state cancer registries, which was completed through 31 December, 2016. The dietary intakes of medium-chain fatty acids were assessed using a validated 89-item food fre-quency questionnaire. Multivariable Cox proportional hazards regression models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations between intakes of medium-chain fatty acids and risk for incident colorectal cancer. Results: Among 71,599 participants, 48,008 (67.3%) were Black individuals and 42,260 (59.0%) were female. A total of 868 incident colorectal cancer cases occurred during a median follow-up of 13.7 y. Comparing the highest to the lowest quartile, high intake of dodecanoic acid/lauric acid (C12:0) was associated with reduced risk of colorectal cancer among White participants (HR: 0.52; 95% CI: 0.30, 0.91; P-trend = 0.05), but not in Black individuals (HR: 0.92; 95% CI, 0.68, 1.24; P-trend = 0.80) in multivariable-adjusted models. No associations were found between intakes of hexanoic acid/caproic acid (C6:0), octanoic acid/caprylic acid (C8:0), or decanoic acid/capric acid (C10:0) and risk of incident colorectal cancer overall or within racial subgroups. Conclusions: In a predominantly low-income United States population, an increased dietary C12:0 intake was associated with a substantially reduced risk of colorectal cancer only among White individuals, but not in Black individuals.

IMPORTANCEEpidemiologic evidence regarding the outcomes of dietary sodium intake on mortality remains limited for low-income individuals, particularly Black people.OBJECTIVETo 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 PARTICIPANTSThis 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.EXPOSURESDietary sodium intake was assessed using a validated food frequency questionnaire at baseline.MAIN OUTCOMES AND MEASURESMultivariable-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.RESULTSAmong the 64 329 participants, 46 185 (71.8%) were Black, 18 144 (28.2%) were White, and 39 155 (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; 37 482 Black individuals (81.2%) and 14 431 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, 17 811 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 RELEVANCEIn this cohort study of 64 329 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.

BACKGROUND:Metformin, utilized to manage hyperglycemia, has been linked to a reduced risk of colorectal cancer (CRC) among individuals with diabetes. However, evidence is lacking for non-Hispanic Black individuals and those with lower socioeconomic status (SES), who face elevated risk for both diabetes and CRC. In this study, we investigated the association between metformin use and incident CRC risk within the Southern Community Cohort Study (SCCS), a racially- and SES-diverse prospective cohort. METHODS:Participants reported their diabetes diagnosis and medications, including metformin, upon enrollment (2002-2009) and during follow-up surveys approximately every five years. Incident cases of CRC were identified through state cancer registries and the National Death Index. Proportional hazards models were employed to explore the relationship between metformin use and CRC risk, adjusted for cancer risk factors. RESULTS:A total of 25,992 participants with diabetes were included in the analysis, among whom 10,095 were taking metformin. Of these participants, 76% identified as non-Hispanic Black, and 60% reported household incomes <$15,000/year. Metformin use was associated with a significantly lower CRC risk (HR [95% CI]: 0.71 [0.55-0.93]), with consistent results for both colon (0.80 [0.59-1.07]) and rectal cancers (0.49 [0.28-0.86]). The protective association appeared to be stronger among non-Hispanic White individuals (0.51 [0.31-0.85]) compared to non-Hispanic Black participants (0.80 [0.59-1.08], p-interaction =.13). Additionally, a protective association was observed among obese individuals (BMI ≥30 kg/m2, 0.59 [0.43-0.82] but not among non-obese participants (0.99 [0.65-1.51], p-interaction =.05) CONCLUSION: Our findings indicate that metformin use is associated with a reduced risk of CRC in individuals with diabetes, including among those from predominantly low SES backgrounds. These results support previous epidemiological findings, and demonstrate that the protective association for metformin in relation to incident CRC likely generalizes to populations with higher underlying risk.

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

Supplementary Table from Sociocultural Factors, Access to Healthcare, and Lifestyle: Multifactorial Indicators in Association with Colorectal Cancer Risk

Supplemental Table 1. The associations a between ACS Guidelines on Nutrition and Physical Activity for Cancer Prevention compliance score and site-specific cancer incidence by baseline health status

ImportanceType 2 diabetes and colorectal cancer (CRC) disproportionately burden indviduals of low socioeconomic status and African American race. Although diabetes is an emerging CRC risk factor, associations between diabetes and CRC in these populations are understudied.ObjectiveTo determine if diabetes is associated with CRC risk in a cohort representing understudied populations.Design, Setting, and ParticipantsThis cohort study uses data from the prospective Southern Community Cohort Study in the US, which recruited from 2002 to 2009 and completed 3 follow-up surveys by 2018. Of about 85 000 participants, 86% enrolled at community health centers, while 14% were enrolled via mail or telephone from the same 12 recruitment states. Participants with less than 2 years of follow-up, previous cancer diagnosis (excluding nonmelanoma skin cancer) at enrollment, missing enrollment diabetes status, diabetes diagnosis before age 30, and without diabetes at enrollment with no follow-up participation were excluded. Data were analyzed from January to September 2023.ExposuresPhysician-diagnosed diabetes and age at diabetes diagnosis were self-reported via survey at enrollment and 3 follow-ups.Main Outcomes and MeasuresDiabetes diagnosis was hypothesized to be positively associated with CRC risk before analysis. Incident CRC was assessed via state cancer registry and National Death Index linkage. Hazard ratios and 95% CIs were obtained via Cox proportional hazard models, using time-varying diabetes exposure.ResultsAmong 54 597 participants, the median (IQR) enrollment age was 51 (46-58) years, 34 786 (64%) were female, 36 170 (66%) were African American, and 28 792 (53%) had income less than $15 000 per year. In total, 289 of 25 992 participants with diabetes developed CRC, vs 197 of 28 605 participants without diabetes. Diabetes was associated with increased CRC risk (hazard ratio [HR], 1.47; 95% CI, 1.21-1.79). Greater associations were observed among participants without colonoscopy screening (HR, 2.07; 95% CI, 1.16-3.67) and with smoking history (HR, 1.62; 95% CI, 1.14-2.31), potentially due to cancer screening differences. Greater associations were also observed for participants with recent diabetes diagnoses (diabetes duration <5 years compared with 5-10 years; HR, 2.55; 95% CI, 1.77-3.67), possibly due to recent screening.Conclusions and RelevanceIn this study where the majority of participants were African American with low socioeconomic status, diabetes was associated with elevated CRC risk, suggesting that diabetes prevention and control may reduce CRC disparities. The association was attenuated for those who completed colonoscopies, highlighting how adverse effects of diabetes-related metabolic dysregulation may be disrupted by preventative screening.

AbstractBackground: Observational studies show high prediagnosis 25-hydroxyvitamin D is associated with lower mortality after colorectal cancer diagnosis. Results from clinical trials suggest vitamin D supplementation may improve outcomes among patients with colorectal cancer. Most studies included few Black Americans, who typically have lower 25-hydroxyvitamin D. We evaluated associations between serum 25-hydroxyvitamin D and mortality after colorectal cancer diagnosis among Black American cases. Methods: Data arose from 218 Black Americans from the Southern Community Cohort Study diagnosed with colorectal cancer during follow-up (age 40–79 at enrollment). Prediagnostic 25-hydroxyvitamin D was measured at enrollment and categorized as deficient (<12 ng/mL), insufficient (12–19.9 ng/mL), or sufficient (≥20 ng/mL). Mortality was determined from the National Death Index. Cox proportional hazards were used to estimate HRs and 95% confidence intervals (CI) for associations between 25-hydroxyvitamin D and mortality. Results: As a continuous exposure, higher 25-hydroxyvitamin D was associated with overall mortality [HR = 0.79 (0.65–0.96) per-SD increase, Ptrend = 0.02] and colorectal cancer–specific mortality [HR = 0.83 (0.64–1.08), Ptrend = 0.16]. For overall mortality, associations were strongest among females [HR = 0.65 (0.42–0.92)], current smokers [HR = 0.61 (0.38–0.98)], and obese participants [HR = 0.47 (0.29–0.77)]. Compared with those with deficiency, participants with sufficient 25-hydroxyvitamin D had lower overall mortality after multivariable adjustment [HR: 0.61 (0.37–1.01)]. Conclusions: Prediagnosis 25-hydroxyvitamin D is inversely associated with overall and colorectal cancer–specific mortality among Black Americans with colorectal cancer. Correcting vitamin D deficiency may improve survival of these patients, particularly for obese individuals and smokers. Impact: Our results support including more Black Americans in trials of vitamin D supplementations to improve colorectal cancer outcomes.

Associations between vitamin D biomarkers and colorectal cancer risk by time since blood draw, African American participants of the Southern Community Cohort Study.

Obesity may increase colorectal cancer (CRC) risk through mechanisms of increased inflammation. Although BMI is the most used adiposity indicator, it may less accurately measure adiposity in Black populations. Herein, we investigate associations between BMI, low albumin as an inflammation biomarker, and CRC risk in a racially diverse cohort. Participant data arise from 71,141 participants of the Southern Community Cohort Study, including 724 incident CRC cases. Within the cohort, 69

Ultra Performance Liquid Chromatography-Mass Spectrometry (UPLC-MS).

Abstract Purpose: Evidence from RCTs suggests vitamin D supplementation may improve colorectal cancer (CRC) outcomes after diagnosis. However, most trials did not include large numbers of Black patients, who typically have lower vitamin D levels. We evaluated associations between vitamin D with all-cause and CRC-specific mortality after CRC diagnosis. Methods: Data arose from 220 participants of the Southern Community Cohort Study diagnosed with incident CRC. Eligible patients were ages 40-79 at enrollment, non-Hispanic Black, English-speaking, and provided a blood sample at enrollment for biomarker measurement. Patients provided information on lifestyle factors, demographics, and personal medical history, primarily via in-person interviews. Concentration of 25-hydroxyvitamin D was measured from blood samples taken at enrollment and were categorized by the Institute of Medicine’s categories of deficient (<12ng/mL), inadequate (12-19.9ng/mL), or adequate (≥20ng/mL). Vital status was obtained through linkages with the National Death Index through December 31, 2020. Cox proportional hazards were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for associations between 25-hydroxyvitamin D concentration and mortality. Statistical models adjusted for the following covariates: age at diagnosis, race, sex, cancer stage, education, income, alcohol intake, smoking history, screening history, obesity, insurance coverage, and physical activity. Results: Circulating 25-hydroxyvitamin D concentration was inversely associated with CRC-specific and all-cause mortality. Specifically, patients with pre-diagnosis 25-hydroxyvitamin D concentration categorized as adequate had reduced all-cause mortality in comparison to participants with deficient vitamin D concentration with a HR of 0.58 (95%CI: 0.35, 0.97). Stronger associations between 25-hydroxyvitamin D concentration and all-cause mortality were observed among participants where blood draw occurred three-five years before diagnosis. Associations were strongest among current smokers where the HR for each per-standard deviation increase of 25-hydroxyvitamin D concentration with all-cause mortality was 0.58 (95%CI: 0.36,0.92), and among obese participants the HR for a per-standard deviation increase of 25-hydroxyvitamin D with all-cause mortality was 0.45 (95%CI: 0.27,0.75). An inverse association was also observed with CRC-specific mortality, although the association was attenuated (HR for per-standard deviation increase of 25-hydroxyvitamin D=0.83; 95%CI: 0.63,1.08). Conclusions: Our findings suggest that pre-diagnosis vitamin D concentration is inversely associated with mortality after a CRC diagnosis among Black individuals. Correcting vitamin D deficiency may be warranted among Black CRC patients, particularly for those who smoke or are obese. Citation Format: Shaneda Warren Andersen, Thomas Lawler, Nikhil K. Khankari, Xiao-Ou Shu, Mark D. Steinwandel, Qiuyin Cai, Peter W. Peter W Jurutka, Wei Zheng. Pre-diagnostic vitamin D in association with colorectal cancer- and all-cause mortality: a prospective study among a non-Hispanic Black cohort [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1909.

Higher 25-hydroxyvitamin D is associated with lower colorectal cancer (CRC) risk, with limited data from Af-rican 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-hydroxyvi-tamin 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.