Associations of diabetes and mortality among colorectal cancer patients from the Southern Community Cohort Study.

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.

Age at lung cancer diagnosis in females versus males who never smoke by race and ethnicity.

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 Hawai'i 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.

Associations between Folate and Alcohol Consumption with Colorectal Tumor Ki67 Expression in the Southern Community Cohort Study.

Folate is hypothesized to accelerate cell proliferation in colorectal cancer (CRC) by supporting DNA synthesis, while alcohol is also linked to gastrointestinal epithelial proliferation, despite biological antagonism of folate. We report associations between folate and alcohol consumption with the proliferation marker Ki67 in CRC tumors from the Southern Community Cohort Study. Tumor samples were obtained from formalin-fixed paraffin-embedded tissue blocks. The percentage of cells expressing Ki67 was measured immunohistochemically. Exposures were assessed via questionnaire pre-diagnosis. Associations were assessed via linear regression. In 248 cases (40-78 years), neither dietary folate, folic acid supplements, nor total folate intake were associated with Ki67. Folic acid supplement use was associated with Ki67 in distal/rectal tumors (ß [95% confidence interval]: 7.5 [1.2-13.8], p = .02) but not proximal tumors (-1.4 [-7.1-4.3], p=.62). A positive trend for total folate was observed for distal/rectal tumors (1.6 [0.0-3.3] per 200 µcg, p-trend=.05). Heavy drinking (women: ≥1 drink/day, men: ≥2 drinks/day) was associated with higher Ki67 (6.4 [1.0-11.9], vs. nondrinkers, p=.02), especially for distal/rectal tumors (10.4 [1.6-19.1], p=.02). Negative interaction between alcohol, total folate was observed for distal/rectal tumors (p-interaction=.06). Modest associations between folate, alcohol consumption and distal/rectal tumor Ki67 expression suggest accelerated proliferation, consistent with folate's role in DNA synthesis.

Associations of Depressive Symptoms With All-Cause and Cause-Specific Mortality by Race in a Population of Low Socioeconomic Status: A Report From the Southern Community Cohort Study.

Depression is a leading cause of disability in the United States, but its impact on mortality rates among racially diverse populations of low socioeconomic status is largely unknown. Using data from the Southern Community Cohort Study, 2002-2015, we prospectively evaluated the associations of depressive symptoms with all-cause and cause-specific mortality in 67,781 Black (72.3%) and White (27.7%) adults, a population predominantly with a low socioeconomic status. Baseline depressive symptoms were assessed using the 10-item Center for Epidemiological Studies Depression Scale. The median follow-up time was 10.0 years. Multivariate Cox regression was used to estimate hazard ratios and 95% confidence intervals for death in association with depressive symptoms. Mild, moderate, and severe depressive symptoms were associated with increased all-cause (hazard ratio (HR) = 1.12, 95% confidence interval (CI): 1.03, 1.22; HR = 1.17, 95% CI: 1.06, 1.29; HR = 1.15, 95% CI: 1.03, 1.28, respectively) and cardiovascular disease-associated death (HR = 1.23, 95% CI: 1.05, 1.44; HR = 1.18, 95% CI: 0.98, 1.42; HR = 1.43, 95% CI: 1.17, 1.75, respectively) in Whites but not in Blacks (P for interaction < 0.001, for both). Mild, moderate, or severe depressive symptoms were associated with increased rates of external-cause mortality in both races (HR = 1.24, 95% CI: 1.05, 1.46; HR = 1.31, 95% CI: 1.06, 1.61; HR = 1.42, 95% CI: 1.11, 1.81, respectively; for all study subjects, P for interaction = 0.48). No association was observed for cancer-associated deaths. Our study showed that the association between depression and death differed by race and cause of death in individuals with a low socioeconomic status.

Food intake of folate, folic acid and other B vitamins with lung cancer risk in a low-income population in the Southeastern United States.

PURPOSE: We prospectively examined associations of lung cancer risk with food intake of B vitamins involved in one-carbon metabolism and the use of folic acid-containing supplements among a low-income population of black and white adults in the Southeastern US. METHODS: Within the Southern Community Cohort Study, we included 1064 incident lung cancer cases among 68,236 participants aged 40-79 years at study enrollment. Food intake and the use of folic acid-containing supplements were assessed using a validated food frequency questionnaire at study enrollment. Multivariate Cox regression was used to estimate hazards ratios (HRs) and the 95% confidence intervals (CIs). RESULTS: Folate and/or folic acid intake from food were not associated with lung cancer risk; HRs (95% CI) for highest compared with lowest quartile were 1.08 (0.91-1.29) for total dietary folate, 1.00 (0.84-1.19) for food folate, and 1.09 (0.91-1.30) for food folic acid, respectively. Similarly, no associations were observed after stratifying by sex, race and smoking status, except for a positive association with total dietary folate intake among black women (HR 1.46, 95% CI 1.04-2.05 for the highest quartile compared with the lowest quartile, P trend = 0.02). Neither the use of folic acid-containing supplements nor food intake of vitamin B6, vitamin B12 and riboflavin were associated with lung cancer risk. CONCLUSIONS: Our findings do not support a protective effect of folate or folic acid for lung cancer prevention in a low-income population of black and white adults in the Southeastern US. Our finding of a positive association with total dietary folate intake among black women needs to be interpreted with caution and replicated in other studies.

Prospective study of oral microbiome and colorectal cancer risk in low-income and African American populations.

Oral microbiome may play an important role in cancer pathogenesis. However, no study has prospectively investigated the association of the oral microbiome with subsequent risk of developing colorectal cancer (CRC). We conducted a nested case-control study including 231 incident CRC cases and 462 controls within the Southern Community Cohort Study with 75% of the subjects being African-Americans. The controls were individually matched to cases based on age, ethnic group, smoking, season-of-study enrollment and recruitment method. Oral microbiota were assessed using 16S rRNA gene sequencing in pre-diagnostic mouth rinse samples. Multiple bacterial taxa showed an association with CRC risk at p <0.05. Oral pathogens Treponema denticola and Prevotella intermedia were associated with an increased risk of CRC, with odds ratios (ORs) and 95% confidence intervals (CIs) of 1.76(1.19-2.60) and 1.55(1.08-2.22), respectively, for the individuals carrying these bacteria compared to non-carriers. In the phylum Actinobacteria, Bifidobacteriaceae was more abundant among CRC patients than among controls. In the phylum Bacteroidetes, Prevotella denticola and Prevotella sp. oral taxon 300 were associated with an increased CRC risk, while Prevotella melaninogenica was associated with a decreased risk of CRC. In the phylum Firmicutes, Carnobacteriaceae, Streptococcaceae, Erysipelotrichaceae, Streptococcus, Solobacterium, Streptococcus sp. oral taxon 058 and Solobacterium moorei showed associations with a decreased risk of CRC. Most of these associations were observed among both African- and European-Americans. Most of the associations were not significant after Bonferroni correction for multiple testing, which may be conservative. Our study suggests that the oral microbiome may play a significant role in CRC etiology.

Healthy Eating and Risks of Total and Cause-Specific Death among Low-Income Populations of African-Americans and Other Adults in the Southeastern United States: A Prospective Cohort Study.

BACKGROUND: A healthy diet, as defined by the US Dietary Guidelines for Americans (DGA), has been associated with lower morbidity and mortality from major chronic diseases in studies conducted in predominantly non-Hispanic white individuals. It is unknown whether this association can be extrapolated to African-Americans and low-income populations. METHODS AND FINDINGS: We examined the associations of adherence to the DGA with total and cause-specific mortality in the Southern Community Cohort Study, a prospective study that recruited 84,735 American adults, aged 40-79 y, from 12 southeastern US states during 2002-2009, mostly through community health centers that serve low-income populations. The present analysis included 50,434 African-Americans, 24,054 white individuals, and 3,084 individuals of other racial/ethnic groups, among whom 42,759 participants had an annual household income less than US$15,000. Usual dietary intakes were assessed using a validated food frequency questionnaire at baseline. Adherence to the DGA was measured by the Healthy Eating Index (HEI), 2010 and 2005 editions (HEI-2010 and HEI-2005, respectively). During a mean follow-up of 6.2 y, 6,906 deaths were identified, including 2,244 from cardiovascular disease, 1,794 from cancer, and 2,550 from other diseases. A higher HEI-2010 score was associated with lower risks of disease death, with adjusted hazard ratios (HRs) of 0.80 (95% CI, 0.73-0.86) for all-disease mortality, 0.81 (95% CI, 0.70-0.94) for cardiovascular disease mortality, 0.81 (95% CI, 0.69-0.95) for cancer mortality, and 0.77 (95% CI, 0.67-0.88) for other disease mortality, when comparing the highest quintile with the lowest (all p-values for trend < 0.05). Similar inverse associations between HEI-2010 score and mortality were observed regardless of sex, race, and income (all p-values for interaction > 0.50). Several component scores in the HEI-2010, including whole grains, dairy, seafood and plant proteins, and ratio of unsaturated to saturated fatty acids, showed significant inverse associations with total mortality. HEI-2005 score was also associated with lower disease mortality, with a HR of 0.86 (95% CI, 0.79-0.93) when comparing extreme quintiles. Given the observational study design, however, residual confounding cannot be completely ruled out. In addition, future studies are needed to evaluate the generalizability of these findings to African-Americans of other socioeconomic status. CONCLUSIONS: Our results showed, to our knowledge for the first time, that adherence to the DGA was associated with lower total and cause-specific mortality in a low-income population, including a large proportion of African-Americans, living in the southeastern US.

Dietary medium-chain fatty acids and risk of incident colorectal cancer in a predominantly low-income population: a report from the Southern Community Cohort Study.

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 frequency 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.

Association of cardiometabolic comorbidities with mortality among low-income Black and White Americans.

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.

Sitting Time, Physical Activity and Mortality: A Cohort Study In Low-Income Older Americans.

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.

Metformin's role in lowering colorectal cancer risk among individuals with diabetes from the Southern Community Cohort Study.

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.

Sodium Intake and Cause-Specific Mortality Among Predominantly Low-Income Black and White US Residents.

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 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 RELEVANCE: In 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.

Feasibility of precision smoking treatment in a low-income community setting: results of a pilot randomized controlled trial in The Southern Community Cohort Study.

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.

Associations of Albumin and BMI with Colorectal Cancer Risk in the Southern Community Cohort Study: a Prospective Cohort Study.

BACKGROUND: 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. METHODS: Participant data arise from 71,141 participants of the Southern Community Cohort Study, including 724 incident CRC cases. Within the cohort, 69% are Black. Blood serum albumin concentrations, from samples taken at enrollment, were available for 235 cases and 567 controls. Controls matched by age, sex, and race were selected through incidence density sampling. Cox proportional hazards calculated BMI and CRC risk associations (hazard ratios [HRs]; 95% confidence intervals [CIs]. Conditional logistic regression calculated albumin and CRC risk associations (odds ratios [ORs]; 95%CIs). RESULTS: Underweight, but not overweight or obese, compared to normal BMI was associated with increased CRC risk (HR:1.75, 95%CI:1.00-3.09). Each standard deviation increase of albumin was associated with decreased CRC risk, particularly for those who self-identified as non-Hispanic Black (OR: 0.56, 95%CI:0.34-0.91), or female (OR:0.54, 95%CI:0.30-0.98), but there was no evidence for interaction by these variables (p-interactions > 0.05). Moreover, albumin concentration was lower in Black than White participants. Mediation analysis suggested that the relation between albumin and CRC was not mediated by BMI. CONCLUSIONS: Null associations of overweight/obesity with CRC risk demonstrates limited utility of BMI, especially among Black populations. Low albumin may indicate CRC risk. In Black individuals, albumin may better predict adiposity related risks than BMI.

Associations between serum vitamin D biomarkers and tumor expression of Ki67, p53, and COX-2 in colorectal cancer cases from the Southern Community Cohort Study.

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.

Genome-wide association study (GWAS) of circulating vitamin D outcomes among individuals of African ancestry.

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.

Prediagnostic 25-Hydroxyvitamin D in Association with Cancer-specific and All-cause Mortality among Low-income, Non-Hispanic Black Americans with Colorectal Cancer.

BACKGROUND: 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.

Type 2 Diabetes and Colorectal Cancer Risk.

Importance: Type 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. Objective: To determine if diabetes is associated with CRC risk in a cohort representing understudied populations. Design, Setting, and Participants: This 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. Exposures: Physician-diagnosed diabetes and age at diabetes diagnosis were self-reported via survey at enrollment and 3 follow-ups. Main Outcomes and Measures: Diabetes 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. Results: Among 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 Relevance: In 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.

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

Black Americans of low socioeconomic status (SES) have higher colorectal cancer incidence than other groups in the United States. However, much of the research that identifies colorectal cancer risk factors is conducted in cohorts of high SES and non-Hispanic White participants. Adult participants of the Southern Community Cohort Study (N = 75,182) were followed for a median of 12.25 years where 742 incident colorectal cancers were identified. The majority of the cohort are non-Hispanic White or Black and have low household income. Cox models were used to estimate HRs for colorectal cancer incidence associated with sociocultural factors, access to and use of healthcare, and healthy lifestyle scores to represent healthy eating, alcohol intake, smoking, and physical activity. The association between Black race and colorectal cancer was consistent and not diminished by accounting for SES, access to healthcare, or healthy lifestyle [HR = 1.34; 95% confidence interval (CI),1.10-1.63]. Colorectal cancer screening was a strong, risk reduction factor for colorectal cancer (HR = 0.65; 95% CI, 0.55-0.78), and among colorectal cancer-screened, Black race was not associated with risk. Participants with high school education were at lower colorectal cancer risk (HR = 0.81; 95% CI, 0.67-0.98). Income and neighborhood-level SES were not strongly associated with colorectal cancer risk. Whereas individual health behaviors were not associated with risk, participants that reported adhering to ≥3 health behaviors had a 19% (95% CI, 1-34) decreased colorectal cancer risk compared with participants that reported ≤1 behaviors. The association was consistent in fully-adjusted models, although HRs were no longer significant. Colorectal cancer screening, education, and a lifestyle that includes healthy behaviors lowers colorectal cancer risk. Racial disparities in colorectal cancer risk may be diminished by colorectal cancer screening. PREVENTION RELEVANCE: Colorectal cancer risk may be reduced through screening, higher educational attainment and performing more health behaviors. Importantly, our data show that colorectal cancer screening is an important colorectal cancer prevention strategy to eliminate the racial disparity in colorectal cancer risk. See related Spotlight, p. 561.

Associations of Dietary Intakes of Carotenoids and Vitamin A with Lung Cancer Risk in a Low-Income Population in the Southeastern United States.

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.