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BackgroundIdentifying genetic variants with pleiotropic associations across multiple cancers can reveal shared biologic pathways. Prior pleiotropic studies have primarily focused on European-descent individuals. Yet population-specific genetic variation can occur, and potential pleiotropic associations among diverse racial/ethnic populations could be missed. We examined cross-cancer pleiotropic associations with lung cancer risk in African Americans.MethodsWe conducted a pleiotropic analysis among 1,410 African American lung cancer cases and 2,843 controls. We examined 36,958 variants previously associated (or in linkage disequilibrium) with cancer in prior genome-wide association studies. Logistic regression analyses were conducted, adjusting for age, sex, global ancestry, study site, and smoking status.ResultsWe identified three novel genomic regions significantly associated (FDR-corrected P

Background: African Americans have the highest lung cancer mortality in the United States. Genome-wide association studies (GWASs) of germline variants influencing lung cancer survival have not yet been conducted with African Americans. We examined five previously reported GWAS catalog variants and explored additional genome-wide associations among African American lung cancer cases.Methods: Incident non-small cell lung cancer cases (N = 286) in the Southern Community Cohort Study were genotyped on the Illumina HumanExome BeadChip. We used Cox proportional hazards models to estimate HRs and 95% confidence intervals (CIs) for overall mortality. Two independent African American studies (N = 316 and 298) were used for replication.Results: One previously reported variant, rs1878022 on 12q23.3, was significantly associated with mortality (HR = 0.70; 95% CI: 0.54-0.92). Replication findings were in the same direction, although attenuated (HR = 0.87 and 0.94). Meta-analysis had a HR of 0.83 (95% CI, 0.71-0.97). Analysis of common variants identified an association between chromosome 6q21.33 and mortality (HR = 0.46; 95% CI, 0.33-0.66).Conclusions: We identified an association between rs1878022 in CMKLR1 and lung cancer survival. However, our results in African Americans have a different direction of effect compared with a prior study in European Americans, suggesting a different genetic architecture or presence of gene-environment interactions. We also identified variants on chromosome 6 within the gene-rich HLA region, which has been previously implicated in lung cancer risk and survival.Impact: We found evidence that inherited genetic risk factors influence lung cancer survival in African Americans. Replication in additional populations is necessary to confirm potential genetic differences in lung cancer survival across populations. Cancer Epidemiol Biomarkers Prev; 26(8); 1288-95. ©2017 AACR.

BackgroundGenome-wide association studies (GWAS) in European populations have identified genetic risk variants associated with multiple myeloma.MethodsWe performed association testing of common variation in eight regions in 1,318 patients with multiple myeloma and 1,480 controls of European ancestry and 1,305 patients with multiple myeloma and 7,078 controls of African ancestry and conducted a meta-analysis to localize the signals, with epigenetic annotation used to predict functionality.ResultsWe found that variants in 7p15.3, 17p11.2, 22q13.1 were statistically significantly (P < 0.05) associated with multiple myeloma risk in persons of African ancestry and persons of European ancestry, and the variant in 3p22.1 was associated in European ancestry only. In a combined African ancestry-European ancestry meta-analysis, variation in five regions (2p23.3, 3p22.1, 7p15.3, 17p11.2, 22q13.1) was statistically significantly associated with multiple myeloma risk. In 3p22.1, the correlated variants clustered within the gene body of ULK4 Correlated variants in 7p15.3 clustered around an enhancer at the 3' end of the CDCA7L transcription termination site. A missense variant at 17p11.2 (rs34562254, Pro251Leu, OR, 1.32; P = 2.93 × 10-7) in TNFRSF13B encodes a lymphocyte-specific protein in the TNF receptor family that interacts with the NF-κB pathway. SNPs correlated with the index signal in 22q13.1 cluster around the promoter and enhancer regions of CBX7 CONCLUSIONS: We found that reported multiple myeloma susceptibility regions contain risk variants important across populations, supporting the use of multiple racial/ethnic groups with different underlying genetic architecture to enhance the localization and identification of putatively functional alleles.ImpactA subset of reported risk loci for multiple myeloma has consistent effects across populations and is likely to be functional. Cancer Epidemiol Biomarkers Prev; 25(12); 1609-18. ©2016 AACR.

Medically underserved populations in the United States continue to experience higher cancer burdens of incidence, mortality, and other cancer-related outcomes. It is imperative to understand how health inequities experienced by diverse population groups may contribute to our increasing unequal cancer burdens and disparate outcomes. The National Cancer Institute convened a diverse group of scientists to discuss research challenges and opportunities for cancer epidemiology in medically underserved and understudied populations. This report summarizes salient issues and discusses five recommendations from the group, including the next steps required to better examine and address cancer burden in the United States among our rapidly increasing diverse and understudied populations. Cancer Epidemiol Biomarkers Prev; 25(4); 573-80. ©2016 AACR SEE ALL ARTICLES IN THIS CEBP FOCUS SECTION, "MULTILEVEL APPROACHES TO ADDRESSING CANCER HEALTH DISPARITIES".

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

Background: The history of gestational diabetes mellitus (GDM) has been associated with breast cancer risk in some studies, particularly in young women, but results of cohort studies are conflicting.Methods: We pooled data from 257 290 young (age <55 years) women from five cohorts. We used multivariable Cox proportional-hazards regression to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between GDM history and risk of breast cancer, overall and by oestrogen receptor (ER) status, before age 55 years, adjusted for established breast cancer risk factors.Results: Five percent of women reported a history of GDM and 6842 women reported an incident breast-cancer diagnosis (median follow-up = 16 years; maximum = 24 years). Compared with parous women without GDM, women with a history of GDM were not at increased risk of young-onset breast cancer overall (HR = 0.90; 95% CI: 0.78, 1.03) or by ER status (HR = 0.96; 95% CI: 0.79, 1.16 for ER-positive; HR = 1.07; 95% CI: 0.78, 1.47 for ER-negative). Compared with nulliparous women, parous women with a history of GDM had a lower risk of breast cancer overall (HR = 0.79; 95% CI: 0.68, 0.91) and of ER-positive (HR = 0.82; 95% CI: 0.66, 1.02) but not ER-negative (HR = 1.09; 95% CI: 0.76, 1.54) invasive breast cancer. These results were consistent with the HRs comparing parous women without GDM to nulliparous women.Conclusions: Results of this analysis do not support the hypothesis that GDM is a risk factor for breast cancer in young women. Our findings suggest that the well-established protective effect of parity on risk of ER-positive breast cancer persists even for pregnancies complicated by GDM. [ABSTRACT FROM AUTHOR]

There is limited evidence on the association between red meat consumption and pancreatic cancer among ethnic minorities. We assessed this relationship in two large prospective cohorts: the Multiethnic Cohort Study (MEC) and the Southern Community Cohort Study (SCCS). Demographic, dietary and other risk factor data were collected at cohort entry. Red meat intake was assessed using cohort‐specific validated food frequency questionnaires. Incident pancreatic cancer cases were identified via linkages to state cancer registries. Cox regression was used to calculate relative risks (RRs) and 95% confidence intervals (CIs) for the association of red meat intake with pancreatic cancer risk in each cohort. We performed additional analyses to evaluate cooking methods, mutagens and effect modification by NAT1/2 genotypes. From a total of 184 542 (MEC) and 66 793 (SCCS) at‐risk participants, we identified 1618 (MEC) and 266 (SCCS) incident pancreatic cancer cases. Red meat consumption was associated with pancreatic cancer risk in the MEC (RRQ4vsQ1 1.18, 95% CI 1.02‐1.37) and with borderline statistical significance in the SCCS (RRQ4vsQ1 1.31, 95% CI 0.93‐1.86). This association was significant in African Americans (RRQ4vsQ1 1.49, 95% CI 1.06‐2.11) and Latinos (RRQ4vsQ1 1.44, 95% CI 1.02‐2.04) in the MEC, and among African Americans (RRQ4vsQ1 1.55, 95% CI 1.03‐2.33) in the SCCS. NAT2 genotypes appeared to modify the relationship between red meat and pancreatic cancer in the MEC (pinteraction = 0.03). Our findings suggest that the associations for red meat may be strongest in African Americans and Latinos. The mechanisms underlying the increased risk for these populations should be further investigated. What's new? Studies in white populations indicate that eating red meat may boost pancreatic cancer risk. These authors investigated this association in ethnic minorities in the US. They also looked at cooking methods, mutagens such as heterocyclic aromatic amines (HAAs), and genetic variants in the enzymes N‐acetyltransferase 1/2 (NAT1/2), which impact a person's ability to neutralize these mutagens. By analyzing data from two large ethnically diverse cohorts, they found a significant association between red meat consumption and pancreatic cancer in African Americans and Latinos. They also found that NAT2 genotypes may play a role in this association. [ABSTRACT FROM AUTHOR]

Background: Coenzyme Q10 (CoQ10) is a ubiquitous molecule in living organisms serving as a cofactor in energy production. Epidemiological studies have reported low CoQ10 levels being associated with an increased risk of various cancers. We conducted the first study to evaluate the association of CoQ10 concentrations with lung cancer risk. Methods: A nested case‐control study including 201 lung cancer cases and 395 matched controls from the Southern Community Cohort Study was conducted. Plasma CoQ10 levels were measured using high‐performance liquid chromatography with photo‐diode array detection. Conditional logistic regression models were applied to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between plasma CoQ10 levels and lung cancer risk. Results: Plasma CoQ10 concentration was inversely associated with the risk of lung cancer. After adjusting for age, sex, race, and socioeconomic status, the OR (95% CI) comparing the third to first tertile was 0.57 (0.36–0.91, P for trend = 0.02). Further adjustments for smoking, alcohol, chronic obstructive pulmonary disease, and body mass index attenuated the point estimate slightly (OR = 0.60, 95% CI = 0.34–1.08, P for trend = 0.11), comparing third to first tertiles. Stratified analyses identified a significant inverse association between plasma CoQ10 levels and lung cancer risk in current smokers, but not in former/never smokers. The association was more evident in cases who were diagnosed within 1 year of blood draw than in cases diagnosed after 1 year. Conclusions: Low plasma CoQ10 was significantly associated with increased lung cancer risk, particularly among current smokers. The stronger association seen shortly following the blood draw suggests that CoQ10 may be related to disease progression. [ABSTRACT FROM AUTHOR]

Background--There is a paucity of data on heart failure (HF) incidence among low-income and minority populations. Our objective was to investigate HF incidence and post-HF survival by race and sex among low-income adults in the southeastern United States. Methods and Results--Participants were 27 078 white and black men and women enrolled during 2002 to 2009 in the SCCS (Southern Community Cohort Study) who had no history of HF and were receiving Centers for Medicare and Medicaid Services. Incident HF diagnoses through December 31, 2010 were ascertained using International Classification of Diseases 9th Revision codes 428.x via linkage with Centers for Medicare and Medicaid Services research files. Most participants were black (68.8%), women (62.6%), and earned <$15 000/y (69.7%); mean age was 55.5 (10.4) years. Risk factors for HF were common: hypertension (62.5%), diabetes mellitus (26.5%), myocardial infarction (8.6%), and obesity (44.8%). Over a median follow-up of 5.2 years, 4341 participants were diagnosed with HF. The age-standardized incidence rates were 34.8, 37.3, 34.9, and 35.6/1000 person-years in white women, white men, black men, and black women, respectively, remarkably higher than previously reported. Among HF cases, 952 deaths occurred over a median follow-up of 2.3 years. Men had lower survival; hazard ratios and 95% confidence intervals were 1.63 (1.27-2.08), 1.38 (1.11-1.72), and 0.90 (0.73-1.12) for white men, black men, and black women compared with white women. Conclusions--In this low-income population, HF incidence was higher for all race-sex groups than previously reported in other cohorts. The SCCS is a unique resource to investigate determinants of HF risk in a segment of the population underrepresented in other existing cohorts. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Prior studies of risk factors associated with external causes of death have been limited in the number of covariates investigated and external causes examined. Herein, associations between numerous demographic, lifestyle, and health-related factors and the major causes of external mortality, such as suicide, homicide, and accident, were assessed prospectively among 73,422 black and white participants in the Southern Community Cohort Study (SCCS). Hazard ratios (HR) and 95% confidence intervals (CI) were calculated in multivariate regression analyses using the Cox proportional hazards model. Men compared with women (HR = 2.32; 95% CI: 1.87–2.89), current smokers (HR = 1.74; 95% CI: 1.40–2.17), and unemployed/never employed participants at the time of enrollment (HR = 1.67; 95% CI 1.38–2.02) had increased risk of dying from all external causes, with similarly elevated HRs for suicide, homicide, and accidental death among both blacks and whites. Blacks compared with whites had lower risk of accidental death (HR = 0.46; 95% CI: 0.38–0.57) and suicide (HR = 0.55; 95% CI: 0.31–0.99). Blacks and whites in the SCCS had comparable risks of homicide death (HR = 1.05; 95% CI: 0.63–1.76); however, whites in the SCCS had unusually high homicide rates compared with all whites who were resident in the 12 SCCS states, while black SCCS participants had homicide rates similar to those of all blacks residing in the SCCS states. Depression was the strongest risk factor for suicide, while being married was protective against death from homicide in both races. Being overweight/obese at enrollment was associated with reduced risks in all external causes of death, and the number of comorbid conditions was a risk factor for iatrogenic deaths. Most risk factors identified in earlier studies of external causes of death were confirmed in the SCCS cohort, in spite of the low SES of SCCS participants. Results from other epidemiologic cohorts are needed to confirm the novel findings identified in this study. [ABSTRACT FROM AUTHOR]

Biomarkers of selenium are necessary for assessing selenium status in humans, since soil variation hinders estimation of selenium intake from foods. In this study, we measured the concentration of plasma selenium, selenoprotein P (SEPP1), and glutathione peroxidase (GPX3) activity and their interindividual differences in 383 low-income blacks and whites selected from a stratified random sample of adults aged 40–79 years, who were participating in a long-term cohort study in the southeastern United States (US). We assessed the utility of these biomarkers to determine differences in selenium status and their association with demographic, socio-economic, dietary, and other indicators. Dietary selenium intake was assessed using a validated food frequency questionnaire designed for the cohort, matched with region-specific food selenium content, and compared with the US Recommended Dietary Allowances (RDA) set at 55 µg/day. We found that SEPP1, a sensitive biomarker of selenium nutritional status, was significantly lower among blacks than whites (mean 4.4±1.1 vs. 4.7±1.0 mg/L, p = 0.006), with blacks less than half as likely to have highest vs. lowest quartile SEPP1 concentration (Odds Ratio (OR) 0.4, 95% Confidence Interval (CI) 0.2–0.8). The trend in a similar direction was observed for plasma selenium among blacks and whites, (mean 115±15.1 vs. 118±17.7 µg/L, p = 0.08), while GPX3 activity did not differ between blacks and whites (136±33.3 vs. 132±33.5 U/L, p = 0.320). Levels of the three biomarkers were not correlated with estimated dietary selenium intake, except for SEPP1 among 10% of participants with the lowest selenium intake (≤57 µg/day). The findings suggest that SEPP1 may be an effective biomarker of selenium status and disease risk in adults and that low selenium status may disproportionately affect black and white cohort participants. [ABSTRACT FROM AUTHOR]

Increased sedentary behavior and lack of physical activity are associated with increased risk for many chronic diseases. Differences in leisure-time physical activity between African American and white adults have been suggested to partially explain racial disparities in chronic disease outcomes, but expanding the definition of physical activity to include household and occupational activities may reduce or even eliminate racial differences in total physical activity. The objective of this study was to describe patterns of active and sedentary behaviors in black and white adults and to examine these behaviors across demographic measures. Sedentary and physically active behaviors were obtained from a validated physical activity questionnaire in 23,021 black men, 9,899 white men, 32,214 black women, and 15,425 white women (age 40–79) at enrollment into the Southern Community Cohort Study. Descriptive statistics for sedentary time; light, moderate, and vigorous household/occupational activity; sports/exercise; total activity; and meeting current physical activity recommendations via sports/exercise were examined for each race-sex group. Adjusted means were calculated using multiple linear regression models across demographic measures. Study participants spent approximately 60% of waking time in sedentary behaviors. Blacks reported more television viewing time than whites (45 minutes for females, 15 minutes for males), but when sitting time was expressed as a proportion of overall awake time, minimal racial differences were found. Patterns of light, moderate, and vigorous household/occupational activity were similar in all race/sex groups. 2008 Physical Activity Guidelines for Americans were followed by 16% of women and 25% of men independent of race. Overall, black and white men and women in this study spent the majority of their daily time in sedentary behaviors and less than one-fourth followed current guidelines for physical activity. These results indicate that public health campaigns should focus on both reducing sedentary behavior and increasing physical activity in all adult US populations. [ABSTRACT FROM AUTHOR]

Genome-wide association studies (GWAS), conducted mostly in European or Asian descendants, have identified approximately 67 genetic susceptibility loci for breast cancer. Given the large differences in genetic architecture between the African-ancestry genome and genomes of Asians and Europeans, it is important to investigate these loci in African-ancestry populations. We evaluated index SNPs in all 67 breast cancer susceptibility loci identified to date in our study including up to 3,300 African-American women (1,231 cases and 2,069 controls), recruited in the Southern Community Cohort Study (SCCS) and the Nashville Breast Health Study (NBHS). Seven SNPs were statistically significant (P≤0.05) with the risk of overall breast cancer in the same direction as previously reported: rs10069690 (5p15/TERT), rs999737 (14q24/RAD51L1), rs13387042 (2q35/TNP1), rs1219648 (10q26/FGFR2), rs8170 (19p13/BABAM1), rs17817449 (16q12/FTO), and rs13329835 (16q23/DYL2). A marginally significant association (P<0.10) was found for three additional SNPs: rs1045485 (2q33/CASP8), rs4849887 (2q14/INHBB), and rs4808801 (19p13/ELL). Three additional SNPs, including rs1011970 (9p21/CDKN2A/2B), rs941764 (14q32/CCDC88C), and rs17529111 (6q14/FAM46A), showed a significant association in analyses conducted by breast cancer subtype. The risk of breast cancer was elevated with an increasing number of risk variants, as measured by quintile of the genetic risk score, from 1.00 (reference), to 1.75 (1.30–2.37), 1.56 (1.15–2.11), 2.02 (1.50–2.74) and 2.63 (1.96–3.52), respectively, (P = 7.8×10–10). Results from this study highlight the need for large genetic studies in AAs to identify risk variants impacting this population. [ABSTRACT FROM AUTHOR]

The beneficial biologic effects attributed to vitamin D suggest a potential to influence overall mortality. Evidence addressing this hypothesis is limited, especially for African Americans who have a high prevalence of vitamin D insufficiency. The authors conducted a nested case-control study within the prospective Southern Community Cohort Study to relate baseline serum levels of 25-hydroxyvitamin D (25(OH)D) with subsequent mortality. Cases were 1,852 participants who enrolled from 2002 to 2009 and died >12 months postenrollment. Controls (n = 1,852) were matched on race, sex, age, enrollment site, and blood collection date. The odds ratios for quartile 1 (<10.18 ng/mL) versus quartile 4 (>21.64 ng/mL) levels of 25(OH)D were 1.60 (95% confidence interval (CI): 1.20, 2.14) for African Americans and 2.11 (95% CI: 1.39, 3.21) for non-African Americans. The effects were strongest for circulatory disease death, where quartile 1 versus quartile 4 odds ratios were 2.53 (95% CI: 1.44, 4.46) and 3.25 (95% CI: 1.33, 7.93) for African Americans and non-African Americans, respectively. The estimated odds of total mortality were minimized in the 25(OH)D range of 35–40 ng/mL. These findings provide support for the hypothesis that vitamin D status may have an important influence on mortality for both African Americans and non-African Americans. [ABSTRACT FROM PUBLISHER]

Type 2 diabetes (T2D) is up to twice as prevalent among African Americans as Caucasians. Recent genome-wide association studies (GWAS) have identified multiple common genetic risk variants for T2D; however, none of these studies were conducted exclusively among subjects of African ancestry. Investigating these known loci in other populations would be an expedient way to evaluate the generalizability of the current findings. The authors evaluated 29 known T2D loci in a large southeastern US cohort study including 4,288 African Americans (1,554 cases and 2,734 controls) enrolled during 2002–2009. Seven of the 29 single nucleotide polymorphisms (SNPs) examined were found to be associated with T2D risk at P ≤ 0.05, including rs6769511 (IGF2BP2), 2 SNPs in the WFS1 gene (rs4689388 and rs1801214), rs7903146 (TCF7L2), and 3 SNPs in the KCNQ1 gene (rs231362, rs2237892, and rs2237897). Notably, the association for rs7903146 reached the GWAS significance level (P = 3.6 × 10−8), with an odds ratio per T allele of 1.32 (95% confidence interval: 1.20, 1.46). Regional analyses using GWAS data from Vanderbilt University's BioVU DNA biobank showed significant associations (P < 0.05) with 9 loci, though no association was observed for the index SNPs reported in European- or Asian-ancestry populations. These results extend some of the recent GWAS findings to African Americans and may guide future efforts to identify causal variants for T2D. [ABSTRACT FROM PUBLISHER]

Prospective epidemiologic studies generally rely on 1 baseline biologic sample from participants for measurement of prediagnostic biomarkers, assuming that 1 measurement adequately represents the participant's “typical” level. The body of work assessing the reproducibility of circulating serum 25-hydroxyvitamin D (25(OH)D) levels over time focuses almost exclusively on populations of European descent, and data for vitamin D-binding protein (VDBP) are virtually nonexistent. Thus, the authors measured levels of serum 25(OH)D and VDBP twice in samples collected between 2005 and 2008 from 225 participants (155 black, 70 white) in the Southern Community Cohort Study. Reproducibility for 25(OH)D was uniformly high, with adjusted intraclass correlation coefficients (ICCs) of 0.84 (95% confidence interval (CI): 0.79, 0.88) for blacks and 0.92 (95% CI: 0.87, 0.95) for whites, and there was substantial agreement for assignment of 25(OH)D quartile (κ = 0.83, 95% CI: 0.78, 0.87) and vitamin D adequacy status (κ = 0.76, 95% CI: 0.69, 0.83). VDBP levels were highly stable over time, with adjusted ICCs of 0.97 (95% CI: 0.96, 0.98) for blacks and 0.96 (95% CI: 0.93, 0.97) for whites. These findings suggest that single, baseline 25(OH)D and VDBP serum measurements provide reasonably representative measures of these compounds for both white and black adults, demonstrating their utility as epidemiologic biomarkers in prospective studies. [ABSTRACT FROM PUBLISHER]

Objectives: This study aimed to examine the prevalence, trends, and correlates of practitioner-based complementary and alternative medicine (CAM) services use according to race in a socioeconomically disadvantaged population. Design: Included in this cross-sectional analysis were 50,176 African Americans (AAs) and 19,038 whites enrolled into the Southern Community Cohort Study from March 2002 through September 2009. Logistic regression models were used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) of CAM services use associated with participant characteristics. Outcome measures: Outcomes include the prevalence of and trends in use of CAM services during 2002-2009 and correlates of use by race. Results: CAM services use during 2002-2009 was greater among whites (11.7%) than among AAs (8.5%), but no significant temporal trends within the 8-year period were observed. The significant associations were observed for CAM services use with higher educational attainment (OR 1.78, 95% CI: 1.61-1.96 for college versus less than high school), household income (OR 1.61, 95% CI: 1.44-1.81 for ≥$50,000 versus <$15,000), and having a history of a chronic disease (OR 1.34, 95% CI: 1.21-1.47) among both AAs and whites. Significant differences in findings between AAs and whites were seen for age (with a sharp decline in use with older age among AAs but not whites), sex (with the excess of female users more striking among whites), employment (with the unemployed among AAs but not whites more likely to be users), alcohol consumption (with white but not AA drinkers more likely to report CAM services use), and cigarette smoking status (with negative association of use with current smokers more striking among whites). Conclusions: CAM services use is associated with sociodemographic and health-related factors, and racial differences in such use exist. The descriptive findings of this study help supplement the limited information on CAM use among low-income and minority populations in the United States. [ABSTRACT FROM AUTHOR]

Objectives: To examine the relationship between smoking and weight status in adult women and whether this association differed by race. Methods: The study sample consisted of 22,949 African American and 7831 white women enrolled in the Southern Community Cohort Study from 2002 to 2006. Results: Both African American and white current smokers had decreased odds of being overweight or obese compared to normal-weight nonsmokers, and the inverse trends between current smoking and BMI held for both groups. Conclusion: A strong relationship exists between smoking and weight status, with patterns nearly identical for African Americans and white women. [ABSTRACT FROM AUTHOR]

A previous county mortality study of populations living near two nuclear materials processing and fabrication facilities in Westmoreland and Armstrong counties in Pennsylvania (1950-1995) was extended through 2004. Noncancer mortality (1996-2004) and cancer incidence (1990-2004) were also evaluated. Among the Westmoreland and Armstrong populations, 10,547 cancer deaths occurred during the period 1996 through 2004 and the relative risk (RR) based on comparisons with six demographically similar counties in western Pennsylvania was 0.97, that is, almost exactly as expected, and no different from our previously published analyses covering the years 1950-1995. The results based on cancer incidence data were very similar to those based on cancer mortality data. Over the years 1990 though 2004, 39,350 incident cancers were reported among residents of Armstrong and Westmoreland counties and the RR based on the six demographically similar counties was 0.99, that is, almost exactly as expected. The number of deaths from nonmalignant conditions was 36,565 and very close to the number expected (RR 1.01). Overall, no increases in cancer or nonmalignant diseases could be attributed to living in counties with nuclear materials processing and fabrication facilities. [ABSTRACT FROM AUTHOR]

Previous studies of cancer incidence among persons living in municipalities within one mile of two nuclear materials processing and fabrication plants in Pennsylvania were extended for the years 1998-2004. It had been shown that mailing addresses for residents of rural areas often did not reflect the actual municipality of residence and, if not corrected, would bias study results. The previous studies had corrected for this bias. Accordingly for the extended study, we obtained mailing addresses from the Pennsylvania Department of Health (PDH) for 866 persons with cancer who presumably lived in one of eight minor civil divisions (MCDs) near or encompassing the former nuclear facilities, designated as Area 1 in previous studies conducted by the PDH. Street addresses were geocoded and local postmasters were asked to place rural delivery addresses, post office boxes and street addresses that could not be geocoded into the correct MCD of actual residence. Over 15% of the mailing addresses were found not to be within the boundaries of the Area 1 municipalities. After the mailing addresses of individuals with cancer were placed in their proper MCD of residence, the number of persons diagnosed with cancer (n = 708) and confirmed to have lived in Area 1 was as expected (728.4) based on cancer incidence rates in the general population of Pennsylvania (SIR 0.97; 95% CI 0.90-1.05). To further evaluate the patterns of cancer rates near these nuclear facilities and the influence of improved reporting and geocoding of addresses over time, analyses were conducted of publicly available cancer incidence data from 1990 through 2004. Based on mailing addresses, a steady decrease in the number of cancers reported in the Area 1 proximal MCDs was seen, in contrast to a steady rise in the number of cancers reported in seven adjacent but more distant MCDs from the nuclear facilities, designated as Area 2. These patterns were attributed to improvements over time in the geocoding of residential mailing addresses coupled with the gradual elimination and replacement of rural delivery addresses with street addresses. The incorrect placement of mailing addresses in residential Area 1 municipalities prior to about 2002 overestimated the number of cancers occurring among residents living in close proximity to the nuclear facilities and, correspondingly, underestimated the number among Area 2 residents. Summing Area 1 and Area 2 data showed that there was no change in cancer rates over time. These results are consistent with previous studies indicating that living in municipalities near the former Apollo-Parks nuclear facilities was not associated with an increase in cancer occurrence. [ABSTRACT FROM AUTHOR]

False-positive results are inherent in the scientific process of testing hypotheses concerning the determinants of cancer and other human illnesses. Although much of what is known about the etiology of human cancers has arisen from well-conducted epidemiological studies, epidemiology has been increasingly criticized for producing findings that are often sensationalized in the media and fail to be upheld in subsequent studies. Herein we describe examples from cancer epidemiology of likely false-positive findings and discuss conditions under which such results may occur. We suggest general guidelines or principles, including the endorsement of editorial policies requiring the prominent listing of study caveats, which may help reduce the reporting of misleading results. Increased epistemological humility regarding findings in epidemiology would go a long way to diminishing the detrimental effects of false-positive results on the allocation of limited research resources, on the advancement of knowledge of the causes and prevention of cancer, and on the scientific reputation of epidemiology and would help to prevent oversimplified interpretations of results by the media and the public. [ABSTRACT FROM AUTHOR]

Objective. To describe the key contributions of Dr. Joseph K. McLaughlin, Outstanding Scientist of 2004. Methods. We review the scientific literature and indicate how epidemiologic research conducted by Dr. McLaughlin has clarified long-term health effects among persons with breast and other medical implants. Results. Dr. Joseph K. McLaughlin has conducted and directed more research into the long-term effects of human implants than any other scientist worldwide. His insights greatly elucidated the long-term health consequences associated with a variety of implanted devices, including silicone and saline breast implants, hip and knee replacements, temporomandibular and finger joint devices, and pacemakers. By initiating and bringing to fruition a series of innovative epidemiologic investigations. Dr. McLaughlin and his colleagues have provided the scientific basis for making judgments about alleged adverse health effects following cosmetic, reconstructive, and reparative implant surgery. Conclusions. Dr. McLaughlin's seminal investigations have provided reassurance that breast and other implants have not demonstrably increased the risk of cancer or other systemic diseases. The comprehensive and rigorous nature of this research merits his selection as Outstanding Scientist of 2004. [ABSTRACT FROM AUTHOR]

There has been concern that living near nuclear installations might increase the risk of cancer, including childhood leukemia, in surrounding communities. Such concern has been voiced by residents in Armstrong and Westmoreland Counties in Western Pennsylvania in conjunction with the operation of two former nuclear materials processing facilities located in the Apollo borough and the Parks township, just three miles apart. These facilities began operating in 1957 and 1960 and processed uranium and plutonium for commercial and naval applications. To evaluate the possibility of increased cancer rates in communities around the ApolloParks nuclear facilities, a cancer incidence and a cancer mortality survey were conducted. The county mortality findings are reported here. Nearly 40,000 cancer deaths occurred in the population residing in Armstrong and Westmoreland Counties from 1950 through 1995. Each of these two study counties was matched for comparison to three control counties in the same region on the basis of age, race, urbanization, and socioeconomic factors available from the 1990 U.S. Census. There were over 77,000 cancer deaths in the 6 control counties during the 45 y studied. Following similar methods used by the National Cancer Institute, Standardized Mortality Ratios (SMRs) were computed as the ratio of observed numbers of cancers in the study and control counties compared to the expected number derived from general population rates of the United States. Relative risks (RR) were computed as the ratios of the SMRs for the study and the control counties. There were no significant increases in the study counties for any cancer when comparisons were made with either the U.S. population or the control counties. In particular, deaths due to cancers of the lung, bone, liver, and kidney were not more frequent in the study counties than in the control counties. These are the cancers of a priori interest given that uranium and/or plutonium might be expected to concentrate in these tissues. Deaths from all cancers combined also were not increased in the study counties, and the RRs of cancer mortality before the facilities operated (1950-1964), during plant operations (1965-1980) and after plant closure (1980-1995) were similar: 0.96, 0.95 and 0.98, respectively. For childhood leukemia mortality, the relative risk comparing the study counties with their controls before plant start-up was 1.02, while during operations (RR 0.81) and after closure (RR 0.57) the relative risks were lower. The study is limited by the correlational approach and the relatively large size of the geographic areas of the counties studied. [ABSTRACT FROM AUTHOR]

Because nuclear facilities can release radionuclides into the surrounding environment accidentally or during normal operations, there has been public concern over the possibility of adverse health effects. Two former nuclear materials processing facilities in Armstrong County Pennsylvania have been the focus of such public concern for over 20 y. The Apollo and Parks facilities processed uranium and plutonium fuels for use in nuclear applications. To evaluate the possibility of increased cancer rates in the communities near the Apollo-Parks nuclear processing materials plants, cancer incidence rates were assessed for the years 1993-1997, or nearly 40 y after the plants had begun operation in 1957 and 1960, respectively. The rates of cancer were evaluated among the approximately 17,000 persons living in 1 of 8 municipalities encompassing or near these nuclear sites. Numbers of cancers and mailing addresses (n = 935) were obtained from the Pennsylvania Department of Health. Because mailing addresses in small rural areas do not always reflect actual residences within a municipality, each of 935 addresses was validated (and corrections made when indicated) by contacting area postmasters and using Census Bureau geocoding information, street maps, and aerial photographs. Standardized Incidence Ratios (SIRs) were computed as the ratio of observed numbers of cancers in the study area compared to the expected number derived from general population rates of Pennsylvania. Forty percent of the mailing addresses were found not to be within the boundaries of the study municipalities. After excluding these persons who did not reside in one of the eight municipalities near the Apollo-Parks facilities, 581 cancers remained in contrast to 574.0 expected (SIR 1.01; 95% confidence interval 0.93-1.10). Based upon knowledge of the tissues where uranium or plutonium likely would be deposited after intake, cancers of the lung (SIR 0.88), kidney (SIR 1.05), non-Hodgkin's lymphoma (SIR 1.10), liver (SIR 0.61), and bone (2 observed vs. 1.19 expected) were carefully evaluated but no significant excesses were noted at these sites. Cancers of the female breast and thyroid and leukemia also were not significantly increased, as expected since these tissues are not sites where uranium or plutonium would concentrate. Overall, no increase in cancer risk could be attributed to living near the two former nuclear materials processing facilities. However, misleading elevations in cancer risks would have been suggested if mailing addresses had not been corrected to exclude addresses that were not within the boundaries of the municipalities for which population data were available. The study had sufficient power to exclude increased cancer risks of 10% or greater. [ABSTRACT FROM AUTHOR]

Pooled analyses among whites and East Asians have demonstrated positive associations between all-cause mortality and body mass index (BMI), but studies of African Americans have yielded less consistent results. We examined the association between BMI and all-cause mortality in a sample of African Americans pooled from seven prospective cohort studies: NIH-AARP, 1995–2009; Adventist Health Study 2, 2002–2008; Black Women's Health Study, 1995–2009; Cancer Prevention Study II, 1982–2008; Multiethnic Cohort Study, 1993–2007; Prostate, Lung, Colorectal and Ovarian Screening Trial, 1993–2009; Southern Community Cohort Study, 2002–2009. 239,526 African Americans (including 100,175 never smokers without baseline heart disease, stroke, or cancer), age 30–104 (mean 52) and 71% female, were followed up to 26.5 years (mean 11.7). Hazard ratios (HR) and 95% confidence intervals (CI) for mortality were derived from multivariate Cox proportional hazards models. Among healthy, never smokers (11,386 deaths), HRs (CI) for BMI 25–27.4, 27.5–29.9, 30–34.9, 35–39.9, 40–49.9, and 50–60 kg/m2 were 1.02 (0.92–1.12), 1.06 (0.95–1.18), 1.32 (1.18–1.47), 1.54 (1.29–1.83), 1.93 (1.46–2.56), and 1.93 (0.80–4.69), respectively among men and 1.06 (0.99–1.15), 1.15 (1.06–1.25), 1.24 (1.15–1.34), 1.58 (1.43–1.74), 1.80 (1.60–2.02), and 2.31 (1.74–3.07) respectively among women (reference category 22.5–24.9). HRs were highest among those with the highest educational attainment, longest follow-up, and for cardiovascular disease mortality. Obesity was associated with a higher risk of mortality in African Americans, similar to that observed in pooled analyses of whites and East Asians. This study provides compelling evidence to support public health efforts to prevent excess weight gain and obesity in African Americans.

Examines the epidemiology of different types of cancer. Factors predisposing skin cancer in the United States; Incidence rates of stomach cancer in Japan; Occurrence of breast cancer among American women.