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.

Cigarette smoking and malignant melanoma: a case-control study.

BACKGROUND: Several previous studies have reported inverse associations between cigarette smoking and melanoma. Often these studies have not adjusted for ultraviolet (UV) exposure history, skin type, or number of blistering sunburns, which could confound the observed associations between cigarette smoking and melanoma. OBJECTIVE: We sought to assess whether this reported inverse association persists after adjusting for UV exposure, skin type, and number of blistering sunburns. METHODS: We conducted a population-based case-control study (82 patients with melanoma, 164 control subjects). Two control subjects were matched to each patient by age, sex, race, and skin type. Conditional logistic regression models were fit to assess the association between cigarette smoking history and melanoma, with additional adjustments for UV exposure and sunburns. RESULTS: Compared with never smoking, both former (odds ratio 0.43, 95% confidence interval 0.18-1.04) and current (odds ratio 0.65, 95% confidence interval 0.19-2.24) smoking were inversely associated with melanoma, but the associations were not statistically significant. LIMITATIONS: The number of cutaneous nevi was not assessed in this study. In addition, the relatively small number of patients limits the statistical precision of the observed associations. CONCLUSIONS: After matching for age, sex, race, and skin type, and further adjusting for UV exposure and number of sunburns, cigarette smoking was not statistically significantly associated with melanoma risk, but the results were consistent with previous observations of an inverse association.

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.

Family history of cancer and risk of pancreatic cancer: a pooled analysis from the Pancreatic Cancer Cohort Consortium (PanScan).

A family history of pancreatic cancer has consistently been associated with increased risk of pancreatic cancer. However, uncertainty remains about the strength of this association. Results from previous studies suggest a family history of select cancers (i.e., ovarian, breast and colorectal) could also be associated, although not as strongly, with increased risk of pancreatic cancer. We examined the association between a family history of 5 types of cancer (pancreas, prostate, ovarian, breast and colorectal) and risk of pancreatic cancer using data from a collaborative nested case-control study conducted by the Pancreatic Cancer Cohort Consortium. Cases and controls were from cohort studies from the United States, Europe and China, and a case-control study from the Mayo Clinic. Analyses of family history of pancreatic cancer included 1,183 cases and 1,205 controls. A family history of pancreatic cancer in a parent, sibling or child was associated with increased risk of pancreatic cancer [multivariate-adjusted odds ratios (ORs) = 1.76, 95% confidence interval (CI) = 1.19-2.61]. A family history of prostate cancer was also associated with increased risk (OR = 1.45, 95% CI = 1.12-1.89). There were no statistically significant associations with a family history of ovarian cancer (OR = 0.82, 95% CI = 0.52-1.31), breast cancer (OR = 1.21, 95% CI = 0.97-1.51) or colorectal cancer (OR = 1.17, 95% CI = 0.93-1.47). Our results confirm a moderate sized association between a family history of pancreatic cancer and risk of pancreatic cancer and also provide evidence for an association with a family history of prostate cancer worth further study.

Circulating 25-hydroxyvitamin D and risk of pancreatic cancer: Cohort Consortium Vitamin D Pooling Project of Rarer Cancers.

Results from epidemiologic studies examining pancreatic cancer risk and vitamin D intake or 25-hydroxyvitamin D (25(OH)D) concentrations (the best indicator of vitamin D derived from diet and sun) have been inconsistent. Therefore, the authors conducted a pooled nested case-control study of participants from 8 cohorts within the Cohort Consortium Vitamin D Pooling Project of Rarer Cancers (VDPP) (1974-2006) to evaluate whether prediagnostic circulating 25(OH)D concentrations were associated with the development of pancreatic cancer. In total, 952 incident pancreatic adenocarcinoma cases occurred among participants (median follow-up, 6.5 years). Controls (n = 1,333) were matched to each case by cohort, age, sex, race/ethnicity, date of blood draw, and follow-up time. Conditional logistic regression analysis was used to calculate smoking-, body mass index-, and diabetes-adjusted odds ratios and 95% confidence intervals for pancreatic cancer. Clinically relevant 25(OH)D cutpoints were compared with a referent category of 50-<75 nmol/L. No significant associations were observed for participants with lower 25(OH)D status. However, a high 25(OH)D concentration (> or =100 nmol/L) was associated with a statistically significant 2-fold increase in pancreatic cancer risk overall (odds ratio = 2.12, 95% confidence interval: 1.23, 3.64). Given this result, recommendations to increase vitamin D concentrations in healthy persons for the prevention of cancer should be carefully considered.

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.

Alcohol intake and pancreatic cancer: a pooled analysis from the pancreatic cancer cohort consortium (PanScan).

The literature has consistently reported no association between low to moderate alcohol consumption and pancreatic cancer; however, a few studies have shown that high levels of intake may increase risk. Most single studies have limited power to detect associations even in the highest alcohol intake categories or to examine associations by alcohol type. We analyzed these associations using 1,530 pancreatic cancer cases and 1,530 controls from the Pancreatic Cancer Cohort Consortium (PanScan) nested case-control study. Odds ratios (OR) and 95% confidence intervals (95% CI) were calculated using unconditional logistic regression, adjusting for potential confounders. We observed no significant overall association between total alcohol (ethanol) intake and pancreatic cancer risk (OR = 1.38, 95% CI = 0.86-2.23, for 60 or more g/day vs. >0 to <5 g/day). A statistically significant increase in risk was observed among men consuming 45 or more grams of alcohol from liquor per day (OR = 2.23, 95% CI = 1.02-4.87, compared to 0 g/day of alcohol from liquor, P-trend = 0.12), but not among women (OR = 1.35, 95% CI = 0.63-2.87, for 30 or more g/day of alcohol from liquor, compared to none). No associations were noted for wine or beer intake. Overall, no significant increase in risk was observed, but a small effect among heavy drinkers cannot be ruled out.

Cigarette smoking and pancreatic cancer: a pooled analysis from the pancreatic cancer cohort consortium.

Smoking is an established risk factor for pancreatic cancer; however, detailed examination of the association of smoking intensity, smoking duration, and cumulative smoking dose with pancreatic cancer is limited. The authors analyzed pooled data from the international Pancreatic Cancer Cohort Consortium nested case-control study (1,481 cases, 1,539 controls). Odds ratios and 95% confidence intervals were calculated by using unconditional logistic regression. Smoking intensity effects were examined with an excess odds ratio model that was linear in pack-years and exponential in cigarettes smoked per day and its square. When compared with never smokers, current smokers had a significantly elevated risk (odds ratio (OR) = 1.77, 95% confidence interval (CI): 1.38, 2.26). Risk increased significantly with greater intensity (> or =30 cigarettes/day: OR = 1.75, 95% CI: 1.27, 2.42), duration (> or =50 years: OR = 2.13, 95% CI: 1.25, 3.62), and cumulative smoking dose (> or =40 pack-years: OR = 1.78, 95% CI: 1.35, 2.34). Risk more than 15 years after smoking cessation was similar to that for never smokers. Estimates of excess odds ratio per pack-year declined with increasing intensity, suggesting greater risk for total exposure delivered at lower intensity for longer duration than for higher intensity for shorter duration. This finding and the decline in risk after smoking cessation suggest that smoking has a late-stage effect on pancreatic carcinogenesis.

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.

DNA repair gene variants associated with benign breast disease in high cancer risk women.

Benign breast disease (BBD) is a risk factor for breast cancer and may have a heritable component. Deficient DNA repair has been implicated in breast cancer etiology and may exert its effect before BBD, a known precursor. The association between allelic variants in DNA repair genes and BBD was examined in a cohort of women in Washington County, Maryland. BBD was defined by two criteria: (a) a physician diagnosis of BBD or fibrocystic disease and/or (b) a benign breast biopsy. 3,212 women without BBD at baseline were genotyped for 12 candidate single nucleotide polymorphisms in seven DNA repair genes. Of these women, 482 subsequently reported a diagnosis of BBD. The Cox model was used to calculate hazard ratios (HR). Variant alleles of XRCC1 Arg(194)Trp (rs1799782) and ERCC4 Arg(415)Gln (rs1800067) were significantly associated with BBD [HR, 1.36; 95% confidence interval (95% CI), 1.06-1.74 and HR, 1.39; 95% CI, 1.09-1.76, respectively]. Similar estimates were also observed for each of the BBD criterion used. The BBD association for ERCC4 was even stronger among women with a family history of breast cancer (HR, 2.68; 95% CI, 1.52-4.66; P(interaction) = 0.02). This study suggests that variant alleles in DNA repair genes may modify BBD risk, a potential intermediate marker of breast cancer risk, particularly among high-risk subgroups.

Prospective study of JC virus seroreactivity and the development of colorectal cancers and adenomas.

BACKGROUND: Infection with JC virus has been proposed as a risk factor for colorectal cancer. A nested case-control study was conducted to evaluate the association between prediagnostic JC virus antibodies and the risk of incident colorectal cancer and adenomas. METHODS: Two research serum banks were established in Washington County, MD in 1974 and 1989, with the collection of blood samples from >45,000 volunteers. Incident colorectal cancer cases diagnosed through 2006 (n = 611) were identified among participants by linkage to population-based cancer registries, contributing 729 pairs of observations. Cases of adenomatous polyps (n = 123) were identified from participants of the 1989 cohort who reported having a colonoscopy-detected adenoma at follow-up through 2000 with histology confirmed through medical record review. One control was matched to each case on age, sex, race, and date of blood draw, and, for adenoma controls, date of endoscopy. IgG antibodies to JC virus were measured using virus-like particle ELISA. Associations between JC virus seropositivity and colorectal cancer and adenomas were estimated using conditional logistic regression. RESULTS: Overall, there was no association between antibodies to JC virus and colorectal cancer [odds ratio (OR), 0.91; 95% confidence interval (95% CI), 0.71-1.17]. However, a statistically significant positive association between JC virus seropositivity and subsequent adenoma diagnosis was observed among males (OR, 2.31; 95% CI, 1.20-4.46), whereas a statistically significant inverse association was observed among females (OR, 0.31; 95% CI, 0.14-0.67; P for interaction = 0.01), after adjustment for baseline smoking and body mass index. CONCLUSIONS: Overall, JC virus seropositivity was not associated with colorectal cancer development up to 31 years later. Future studies are needed to confirm the adenoma findings.

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.

Single nucleotide polymorphisms in obesity-related genes and all-cause and cause-specific mortality: a prospective cohort study.

BACKGROUND: The aim of this study was to examine the associations between 16 specific single nucleotide polymorphisms (SNPs) in 8 obesity-related genes and overall and cause-specific mortality. We also examined the associations between the SNPs and body mass index (BMI) and change in BMI over time. METHODS: Data were analyzed from 9,919 individuals who participated in two large community-based cohort studies conducted in Washington County, Maryland in 1974 (CLUE I) and 1989 (CLUE II). DNA from blood collected in 1989 was genotyped for 16 SNPs in 8 obesity-related genes: monoamine oxidase A (MAOA), lipoprotein lipase (LPL), paraoxonase 1 and 2 (PON1 and PON2), leptin receptor (LEPR), tumor necrosis factor-alpha (TNFalpha), and peroxisome proliferative activated receptor-gamma and -delta (PPARG and PPARD). Data on height and weight in 1989 (CLUE II baseline) and at age 21 were collected from participants at the time of blood collection. All participants were followed from 1989 to the date of death or the end of follow-up in 2005. Cox proportional hazards regression was used to obtain the relative risk (RR) estimates and 95% confidence intervals (CI) for each SNP and mortality outcomes. RESULTS: The results showed no patterns of association for the selected SNPs and the all-cause and cause-specific mortality outcomes, although statistically significant associations (p < 0.05) were observed between PPARG rs4684847 and all-cause mortality (CC: reference; CT: RR 0.99, 95% CI 0.89, 1.11; TT: RR 0.60, 95% CI 0.39, 0.93) and cancer-related mortality (CC: reference; CT: RR 1.01, 95% CI 0.82, 1.25; TT: RR 0.22, 95% CI 0.06, 0.90) and TNFalpha rs1799964 and cancer-related mortality (TT: reference; CT: RR 1.23, 95% CI 1.03, 1.47; CC: RR 0.83, 95% CI 0.54, 1.28). Additional analyses showed significant associations between SNPs in LEPR with BMI (rs1137101) and change in BMI over time (rs1045895 and rs1137101). CONCLUSION: Findings from this cohort study suggest that the selected SNPs are not associated with overall or cause-specific death, although several LEPR SNPs may be related to BMI and BMI change over time.

An absolute risk model to identify individuals at elevated risk for pancreatic cancer in the general population.

PURPOSE: We developed an absolute risk model to identify individuals in the general population at elevated risk of pancreatic cancer. PATIENTS AND METHODS: Using data on 3,349 cases and 3,654 controls from the PanScan Consortium, we developed a relative risk model for men and women of European ancestry based on non-genetic and genetic risk factors for pancreatic cancer. We estimated absolute risks based on these relative risks and population incidence rates. RESULTS: Our risk model included current smoking (multivariable adjusted odds ratio (OR) and 95% confidence interval: 2.20 [1.84-2.62]), heavy alcohol use (>3 drinks/day) (OR: 1.45 [1.19-1.76]), obesity (body mass index >30 kg/m(2)) (OR: 1.26 [1.09-1.45]), diabetes >3 years (nested case-control OR: 1.57 [1.13-2.18], case-control OR: 1.80 [1.40-2.32]), family history of pancreatic cancer (OR: 1.60 [1.20-2.12]), non-O ABO genotype (AO vs. OO genotype) (OR: 1.23 [1.10-1.37]) to (BB vs. OO genotype) (OR 1.58 [0.97-2.59]), rs3790844(chr1q32.1) (OR: 1.29 [1.19-1.40]), rs401681(5p15.33) (OR: 1.18 [1.10-1.26]) and rs9543325(13q22.1) (OR: 1.27 [1.18-1.36]). The areas under the ROC curve for risk models including only non-genetic factors, only genetic factors, and both non-genetic and genetic factors were 58%, 57% and 61%, respectively. We estimate that fewer than 3/1,000 U.S. non-Hispanic whites have more than a 5% predicted lifetime absolute risk. CONCLUSION: Although absolute risk modeling using established risk factors may help to identify a group of individuals at higher than average risk of pancreatic cancer, the immediate clinical utility of our model is limited. However, a risk model can increase awareness of the various risk factors for pancreatic cancer, including modifiable behaviors.

Allergic rhinitis and secondhand tobacco smoke: a population-based study.

BACKGROUND: Allergic rhinitis (AR) is a common disease that affects approximately one-fifth of the U.S. population. Few studies have evaluated the association between secondhand tobacco smoke (SHS) exposure and the impacts on symptom severity in AR. In this study, we evaluated the association of SHS and AR in a community-based study of adult nonsmokers. METHODS: In Washington County, Maryland, 83 subjects with AR (physician diagnosed or reported skin test positive), and 117 nonallergic subjects from the same community were recruited and interviewed. A validated questionnaire was used to assess past and present SHS exposure as well as disease-specific quality of life. RESULTS: SHS was reported in 34/83 allergic subjects. Compared with AR subjects with no SHS exposure, subjects with AR and SHS were more likely to report a family history of chronic sinusitis (p = 0.04) and use nasal decongestants (p = 0.012). There was also a borderline association with reporting more severe nasal obstruction (p = 0.14) and nasal drainage (p = 0.08). Compared with nonallergic subjects, allergic subjects were more likely to report longer SHS exposure currently (adjusted mean difference = 1.6 hours/week; p = 0.01) and 20 years ago (adjusted mean difference = 2.9 hours/week; p = 0.03). CONCLUSION: Past and current SHS may be a risk factor for AR. Allergic subjects with SHS exposure were more likely to use nasal decongestants and to report more severe nasal symptoms such as nasal obstruction and nasal drainage than nonexposed allergic subjects.

Reliability and sensitivity of the self-report of physician-diagnosed gout in the campaign against cancer and heart disease and the atherosclerosis risk in the community cohorts.

OBJECTIVE: gout is often defined by self-report in epidemiologic studies. Yet the validity of self-reported gout is uncertain. We evaluated the reliability and sensitivity of the self-report of physician-diagnosed gout in the Campaign Against Cancer and Heart Disease (CLUE II) and the Atherosclerosis Risk in the Community (ARIC) cohorts. METHODS: the CLUE II cohort comprises 12,912 individuals who self-reported gout status on either the 2000, 2003, or 2007 questionnaires. We calculated reliability as the percentage of participants reporting having gout on more than 1 questionnaire using Cohen's κ statistic. The ARIC cohort comprises 11,506 individuals who self-reported gout status at visit 4. We considered a hospital discharge diagnosis of gout or use of a gout-specific medication as the standard against which to calculate the sensitivity of self-reported, physician-diagnosed gout. RESULTS: of the 437 CLUE II participants who self-reported physician-diagnosed gout in 2000, and subsequently answered the 2003 questionnaire, 75% reported gout in 2003 (κ = 0.73). Of the 271 participants who reported gout in 2000, 73% again reported gout at the 2007 followup questionnaire (κ = 0.63). In ARIC, 196 participants met the definition for gout prior to visit 4 and self-reported their gout status at visit 4. The sensitivity of a self-report of physician-diagnosed gout was 84%. Accuracy was similar across sex and race subgroups, but differed across hyperuricemia and education strata. CONCLUSION: these 2 population-based US cohorts suggest that self-report of physician-diagnosed gout has good reliability and sensitivity. Thus, self-report of a physician diagnosis of gout is appropriate for epidemiologic studies.

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.

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.