Body-mass index and mortality among 1.46 million white adults.

BACKGROUND: A high body-mass index (BMI, the weight in kilograms divided by the square of the height in meters) is associated with increased mortality from cardiovascular disease and certain cancers, but the precise relationship between BMI and all-cause mortality remains uncertain. METHODS: We used Cox regression to estimate hazard ratios and 95% confidence intervals for an association between BMI and all-cause mortality, adjusting for age, study, physical activity, alcohol consumption, education, and marital status in pooled data from 19 prospective studies encompassing 1.46 million white adults, 19 to 84 years of age (median, 58). RESULTS: The median baseline BMI was 26.2. During a median follow-up period of 10 years (range, 5 to 28), 160,087 deaths were identified. Among healthy participants who never smoked, there was a J-shaped relationship between BMI and all-cause mortality. With a BMI of 22.5 to 24.9 as the reference category, hazard ratios among women were 1.47 (95 percent confidence interval [CI], 1.33 to 1.62) for a BMI of 15.0 to 18.4; 1.14 (95% CI, 1.07 to 1.22) for a BMI of 18.5 to 19.9; 1.00 (95% CI, 0.96 to 1.04) for a BMI of 20.0 to 22.4; 1.13 (95% CI, 1.09 to 1.17) for a BMI of 25.0 to 29.9; 1.44 (95% CI, 1.38 to 1.50) for a BMI of 30.0 to 34.9; 1.88 (95% CI, 1.77 to 2.00) for a BMI of 35.0 to 39.9; and 2.51 (95% CI, 2.30 to 2.73) for a BMI of 40.0 to 49.9. In general, the hazard ratios for the men were similar. Hazard ratios for a BMI below 20.0 were attenuated with longer-term follow-up. CONCLUSIONS: In white adults, overweight and obesity (and possibly underweight) are associated with increased all-cause mortality. All-cause mortality is generally lowest with a BMI of 20.0 to 24.9.

Sun-seeking behavior to increase cutaneous vitamin D synthesis: when prevention messages conflict.

OBJECTIVES: The public has long been encouraged to engage in sun-safe practices to minimize exposure to sunlight, the major cause of nonmelanoma skin cancer. More recently, some have advocated unprotected sun exposure to increase cutaneous synthesis of vitamin D as a way to promote health. We assessed the net result of these conflicting messages. METHODS: In a cross-sectional survey in 2007, questionnaires were mailed to participants of an ongoing cohort study in Washington County, Maryland. The study population consisted of 8,027 adults (55% response rate). RESULTS: Thirty percent of respondents were aware that unprotected sun exposure increased endogenous vitamin D levels. Among those who were aware of this benefit, 42% reported going out into the sun to increase vitamin D levels. Sun-seeking to increase vitamin D production did not significantly differ according to self-reported personal history of skin cancer, but was significantly higher among women, older age groups, those with less education, and vitamin D supplement users. CONCLUSION: A substantial proportion of respondents reported sun-seeking behavior expressly to increase endogenous vitamin D levels. The message about sun exposure and vitamin D is reaching the general public; however, this finding poses challenges to skin cancer prevention efforts.

Association between plasma total cholesterol concentration and incident prostate cancer in the CLUE II cohort.

Statin drugs appear to protect against advanced and possibly high-grade prostate cancer, perhaps through cholesterol-lowering. Thus, we evaluated the association between plasma cholesterol and prostate cancer. We conducted a prospective study in the CLUE II cohort of Washington County, MD. Included were 6,816 male county residents aged 35+ years old who did not have a cancer diagnosis at baseline in 1989. Plasma cholesterol, measured enzymatically at baseline, was categorized by clinical cutpoints. Cox proportional hazards regression was used to estimate multivariable-adjusted hazard ratios (HR) and 95% confidence intervals (CI) for total (n = 438) and high-grade (Gleason sum > or =7, n = 137) prostate cancer. Compared to men with high cholesterol (> or =240 mg/dl), men with desirable (<200 mg/dl) or borderline (200 to <240 mg/dl) levels were less likely to develop high-grade prostate cancer, particularly when restricting to organ-confined cases (HR: 0.68, 95% CI 0.40-1.18; P trend = 0.12) and among men with higher BMI (HR: 0.36, 95% CI 0.16-0.79; P trend = 0.02). Results were unchanged after excluding cholesterol-lowering drug users. Cholesterol was not associated with total prostate cancer. Our study supports two prior ones suggesting that cholesterol influences risk of high-grade prostate cancer, and indirectly supports the hypothesis that cholesterol-lowering is a mechanism by which statins are protective.

Metabolic syndrome components and colorectal adenoma in the CLUE II cohort.

BACKGROUND: Metabolic syndrome components have been associated with colorectal cancer in several studies; however, evidence for colorectal adenomas is limited. Thus, we evaluated the association between markers of the metabolic syndrome with colorectal adenoma development in a nested case-control study. METHODS: Colorectal adenoma cases (n = 132) and matched controls, who had a negative sigmoidoscopy or a colonoscopy (n = 260), were identified between baseline in 1989 and 2000 among participants in the CLUE II cohort of Washington County, Maryland. Concentrations of C-peptide, insulin-like growth factor binding protein-1, glycosylated hemoglobin, total cholesterol, high-density lipoprotein cholesterol, and triglycerides were measured in baseline blood specimens. Body mass index was calculated using baseline height and weight. Use of medications to treat diabetes mellitus was self-reported at baseline. Blood pressure was measured at baseline. Distributional cutpoints of the latter markers were used to define the metabolic syndrome components (hyperinsulinemia, hyperglycemia, obesity, dyslipidemia, and hypertension) present at baseline. RESULTS: No statistically significant associations with adenomas were observed for the markers of the metabolic syndrome, with the exception of a strong positive association for use of diabetes medications (OR, 8.00; 95% CI, 1.70-37.67), albeit based on small numbers. CONCLUSION: Our findings do not support that components of the metabolic syndrome influence risk of colorectal adenomas, except possibly for severe diabetes mellitus warranting medical treatment.

Association of IL10 and other immune response- and obesity-related genes with prostate cancer in CLUE II.

BACKGROUND: Chronic intra-prostatic inflammation and obesity are thought to influence prostate carcinogenesis. Thus, variants in genes in these pathways could be associated with prostate cancer risk. METHODS: We genotyped 17 common single nucleotide polymorphisms (SNPs) in RNASEL, TLR4, IL1B, IL6, IL8, IL10, TNF, CRP, ADIPOQ, LEP, PPARG, and TCF7L2 in 258 white prostate cancer cases and 258 matched controls nested in CLUE II. Single-locus analyses were conducted using conditional logistic regression. TagSNPs were selected in IL10, CRP, and TLR4 and haplotype analyses were done. RESULTS: The A allele of IL10 -1082G>A (rs1800896), known to result in lower levels of this anti-inflammatory cytokine, was positively associated with risk (AG vs. GG, OR = 1.69, 95% CI: 1.10-2.60; AA vs. GG, OR = 1.81, 95% CI: 1.11-2.96; P (trend) = 0.02). Associations of IL10 haplotypes with prostate cancer were explained by high linkage disequilibrium between two tagSNPs (rs1800890 and rs3024496) and -1082G>A. A TLR4 candidate SNP (rs4986790; AG/GG vs. AA, OR = 0.60, 95% CI: 0.33-1.08; P(trend) = 0.09), known to have decreased expression and be associated with lower circulating levels of inflammatory mediators, and tagSNP (rs10116253; CC vs. TT, OR = 3.05, 95% CI: 1.11-8.41), but not haplotypes, were associated with risk. None of the other candidate SNPs or haplotypes was statistically significantly associated with risk. CONCLUSION: Our prospective study suggests that genetic variation in IL10 and possibly TLR4 is associated with prostate cancer risk. Although none of the SNPs in the obesity genes tested was associated, this does not rule out a complex role of obesity and its metabolic consequences in prostate cancer etiology.

Association of common polymorphisms in IL10, and in other genes related to inflammatory response and obesity with colorectal cancer.

OBJECTIVE AND METHODS: The association of 17 candidate single nucleotide polymorphisms (SNPs) in IL10 and other immune response genes (CRP, TLR4, IL6, IL1B, IL8, TNF, RNASEL) and genes related to obesity (PPARG, TCF7L2, ADIPOQ, LEP) with colorectal cancer was investigated. Haplotype tagging SNPs were chosen for IL10, CRP, and TLR4. Incident colorectal cancer cases (n = 208) and matched controls (n = 381) were identified between baseline in 1989 and 2003 among participants in the CLUE II cohort. Odds ratios (OR) and 95% confidence intervals (95% CI) were estimated using conditional logistic regression. RESULTS: Compared with the AA genotype at the candidate IL10-1082 locus (rs1800896), carrying one (OR, 0.79; 95% CI, 0.53-1.18) or two (OR, 0.58; 95% CI, 0.35-0.95) G alleles, a known higher producer of the anti-inflammatory cytokine IL-10, was associated with lower risk of colorectal cancer (p trend = 0.03). Statistically significant associations with colorectal cancer were observed for three tagSNPs in IL10 (rs1800890, rs3024496, rs3024498) and one common haplotype, but these associations were due to high linkage disequilibrium with IL10-1082. Two CRP haplotypes (global p = 0.04) and TLR4 tagSNPs (rs7873784, rs11536891), but not TLR4 haplotypes, were associated with colorectal cancer. CONCLUSIONS: Our study suggests that polymorphisms in IL10, and also possibly in CRP and other genes related to immune response or obesity may be associated with colorectal cancer.

Association between C-peptide concentration and prostate cancer incidence in the CLUE II cohort study.

Diabetes, characterized by perturbations in insulin production and signaling, is inversely associated with prostate cancer risk irrespective of stage. Obesity, a diabetes risk factor, is inversely associated with localized disease but positively associated with advanced disease. To understand the complex association between hyperinsulinemia and prostate cancer, we evaluated the association of plasma C-peptide, an insulin secretion marker, with prostate cancer risk in a case-control study nested in a prospective community cohort. Prostate cancer cases (n = 264) and matched controls (n = 264) were identified in the CLUE II cohort between 1989 (baseline) and 2002. C-peptide concentration was measured in baseline plasma by ELISA. Odds ratios (OR) and 95% confidence intervals (95% CI) were estimated using conditional logistic regression, adjusting for being overweight or obese and family history. Median C-peptide concentration was lower in cases (1,180 pmol/L) than in controls (1,365 pmol/L; P = 0.03). Men in the highest (versus lowest) fourth of C-peptide had a lower risk for prostate cancer (OR, 0.65; 95% CI, 0.37-1.14; P-trend = 0.08), primarily localized disease (OR, 0.44; 95% CI, 0.19-1.03; P-trend = 0.04). Associations were similar to overall, when excluding cases diagnosed during the first 5 years of follow-up, men with diabetes, or men who had not had a prostate-specific antigen test. C-peptide concentration was inversely associated with subsequent diagnosis of prostate cancer, primarily localized disease, similar to the association for obesity. However, we cannot rule out detection bias that might result if men with higher C-peptide have lower prostate-specific antigen irrespective of whether prostate cancer is present or not.

Involving stakeholders to optimize a study protocol on secondhand tobacco smoke and chronic rhinosinusitis in adults.

BACKGROUND: Epidemiological evidence evaluating the association between secondhand smoke exposure and diseases of the upper airway in adults is limited by a small number of studies and a lack of established protocols. This study was designed to optimize a research protocol on secondhand tobacco smoke exposure and chronic rhinosinusitis for a future population-based case-control study in Washington County, Maryland, using a participatory research model. METHODS: We conducted three focus groups with health professionals, community members, and research practitioners for protocol development; 10 one-on-one cognitive testings with community members for protocol refinement; and a pilot testing of the full study protocol (10 cases and 10 controls) for full evaluation of the study protocol. RESULTS: Health professionals recommended, among other themes, enrolling patients with confirmed chronic rhinosinusitis (minimum 12-week symptom duration and objective inflammation). Community members and research practitioners discussed optimal strategies for participant recruitment and interviewing. The protocol, revised with the focus group's feedback, was further evaluated in one-on-one sessions with 10 Washington County residents (3 with chronic rhinosinusitis). In the pilot study, 10 nonsmoking chronic rhinosinusitis cases (5 clinic based and 5 community based) and their community-based age, sex, and former/never smoking-matched controls were recruited. Sinonasal symptoms scores were higher in cases than controls but similar for clinic versus community-based cases. CONCLUSION: This protocol development framework involving stakeholders resulted in a comprehensive questionnaire that was successfully evaluated during a pilot study and is now ready to be used in population-based and clinical epidemiological studies of chronic rhinosinusitis in adults.

Natural history of celiac disease autoimmunity in a USA cohort followed since 1974.

BACKGROUND: The natural history and the possible changes of celiac disease (CD) prevalence over time are still unclear. OBJECTIVES: 1) To establish whether loss of tolerance to gluten may occur at any age; 2) to investigate possible changes of CD prevalence over time; and 3) to investigate CD-related co-morbidities. METHODS: We analyzed 3,511 subjects with matched samples from 1974 (CLUE I) and 1989 (CLUE II). To avoid a selection bias regarding survival, we also screened 840 CLUE I participants who deceased after the 1974 survey. Outcome measure. CD autoimmunity (positivity to auto-antibodies) over time. RESULTS: CD autoimmunity was detected in seven subjects in 1974 (prevalence 1:501) and in an additional nine subjects in 1989 (prevalence 1:219). Two cases of CD autoimmunity were found among the 840 subjects deceased after CLUE I. Compared to controls, untreated CD subjects showed increased incidence of osteoporosis and associated autoimmune disorders, but they did not reach statistical significance. CONCLUSIONS: During a 15-year period CD prevalence increased 2-fold in the CLUE cohort and 5-fold overall in the US since 1974. The CLUE study demonstrated that this increase was due to an increasing number of subjects that lost the immunological tolerance to gluten in their adulthood.

Secondhand tobacco smoke exposure and chronic rhinosinusitis: a population-based case-control study.

BACKGROUND: Rhinosinusitis is a costly disease that adversely affects quality of life (QOL). It is known to be influenced by environmental factors, but few studies have evaluated the association between secondhand tobacco smoke (SHS) exposure and chronic rhinosinusitis (CRS). To address this evidence gap, we evaluated the association of SHS and CRS risk in a community-based case-control study of adult nonsmokers. METHODS: In Washington County, MD, 100 cases with a confirmed diagnosis of CRS and 100 controls matched for age, sex, and smoking status (former-never) were recruited and interviewed. A validated questionnaire was used to assess past and present SHS exposure as well as disease-specific QOL. RESULTS: Compared with those who reported no SHS exposure, current or childhood SHS exposure was associated with significantly increased risk of CRS (odds ratio, 2.33; 95% CI, 1.02, 5.34). CRS cases exposed to SHS (n = 39) had worse mean scores in nasal obstruction/blockage (3.1 versus 2.5; p = 0.02), nasal discharge (3.3 versus 2.7; p = 0.03), headaches (2.4 versus 1.5; p = 0.01), and cough (2.1 versus 1.5; p = 0.04) than cases without SHS exposure (n = 61). Cases exposed to SHS were also more likely to use nasal decongestants (53.9% versus 34.4%; p = 0.05). CONCLUSION: Exposure to SHS during childhood and adulthood may be a risk factor for CRS. Furthermore, compared with unexposed CRS cases, SHS exposed cases reported worse nasal symptoms and used more nasal decongestants compared with unexposed cases, suggesting SHS exposure is related to exacerbation and more severe symptoms.