Abstract
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.
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 ≥7, n = 137) prostate cancer. Compared to men with high cholesterol (≥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.
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.
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.
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.
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.
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).
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.
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.
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. (Cancer Epidemiol Biomarkers Prev 2009;18(1):346–50)
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.
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.
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