Smoking and pancreatic cancer: a sex-specific analysis in the Multiethnic Cohort study

Purpose To examine whether the detrimental smoking-related association with pancreatic cancer (PC) is the same for women as for men. Methods We analyzed data from 192,035 participants aged 45–75 years, enrolled in the Multiethnic Cohort study (MEC) in 1993–1996. We identifed PC cases via linkage to the Hawaii and California Surveillance, Epidemiology, and End Results Program cancer registries through December 2017. Results During a mean follow-up of 19.2 years, we identifed 1,936 incident PC cases. Women smokers smoked on average less than men smokers. In multivariate Cox regression models, as compared with sex-specifc never smokers, current smokers had a similar elevated risk of PC for women, hazard ratio (HR) 1.49 (95% CI 1.24, 1.79) and as for men, HR 1.48 (95% CI 1.22, 1.79) (pheterogeneity: 0.79). Former smokers showed a decrease in risk of PC for men within 5 years, HR 0.74 (95% CI 0.57, 0.97) and for women within 10 years after quitting, HR 0.70 (95% CI 0.50, 0.96), compared with their sex-specifc current smokers. Both sexes showed a consistent, strong, positive dose–response association with PC for the four measures (age at initiation, duration, number of cigarettes per day, number of pack-years) of smoking exposure among current smokers and an inverse association for years of quitting and age at smoking cessation among former smokers (all ptrend’s<0.001). Conclusion Although MEC women smoke on average less than their men counterparts, the smoking-related increase in PC risk and the benefts of cessation seem to be of similar magnitudes for women as for men

Modification of Asphalt Rubber with Nanoclay towards Enhanced Storage Stability

Asphalt rubber (AR), which is prepared by blending crumb rubber and bitumen, provides various advantages, including superior rutting resistance, lower road-tire noise and longer service life. However, contractors have expressed concerns regarding its poor storage stability, which in turn limits its wider application. This study aims to address the storage stability concern by incorporating nano-montmorillonite (nanoclay). Three types of nanoclay were dispersed into hot AR binder by high shear blending. The rheological properties of nanoclay-crumb rubber modifier (CRM)-modified bitumen were evaluated through Superpave performance grade (PG) tests and the storage stability was characterized by measuring the difference in softening points or complex moduli at the top and bottom portions of binders after lab-simulated storage. X-ray diffraction (XRD) evaluation was conducted to observe the variation of nanoclay layer gap distance for mechanism investigation. It was found that all selected nanoclays had insignificant effects on workability, rutting and fatigue properties. The layered nanoclay transformed to intercalated or exfoliated structures after interaction with bitumen fractions, providing superior storage stability. Among the three selected nanoclays, pure montmorillonite with Na+ inorganic group, which has an intermediate hydrophilic property and middle layer gap, showed the most obvious effect on enhancing the storage stability of AR

Association of Serum γ-Tocopherol Levels with Mortality: The Multiethnic Cohort Study

Background/Objectives—γ-Tocopherol has unique properties that protect against nitrogen oxide-mediated cellular damage. To elucidate the potential role of γ-tocopherol in the aging process, we examined the associations of serum γ-tocopherol levels with all-cause and cause-specific mortality. Subjects/Methods—Among participants in the biorepository subcohort of the Multiethnic Cohort Study, pre-cancer diagnostic serum γ-tocopherol levels were measured in a subset of 3904 men and 4461 women. Of these, 22.7% of men and 13.5% of women died during a mean follow- up time of 9.6±2.6 years. Hazard ratios (HRs) and 95% confidence intervals (95%CIs) for mortality associated with γ-tocopherol were estimated by Cox proportional hazards regression. Results—Positive associations of serum γ-tocopherol with all-cause, cancer and cardiovascular disease mortality (CVD) (Ptrend\u3c0.05) were detected after adjusting for age, race-ethnicity and serum cholesterol levels. The respective HRs (95%CIs) for the highest versus the lowest sex- specific γ-tocopherol quartile were 1.43 (1.17–1.74), 1.79 (1.22–2.64), and 1.52 (1.10–2.11) for men and 1.58 (1.25–2.00), 1.59 (1.05–2.41), and 1.59 (1.07–2.37) for women. Associations remained significant for all-cause mortality among women after further adjusting for smoking variables and history of cancer, CVD, diabetes, and hypertension at cohort entry (highest vs. lowest γ-tocopherol quartile: HR=1.38; 95%CI=1.08–1.75; Ptrend= 0.005). Overall, associations with all-cause mortality were consistent across race/ethnicity and were significant in three of ten sex-specific racial/ethnic groups in the fully adjusted models with no interactions between ethnicity and γ-tocopherol. Conclusions—The positive association between γ-tocopherol and mortality suggests a potential physiological role for γ-tocopherol in response to pathological conditions

Predicting total, abdominal, visceral and hepatic adiposity with circulating biomarkers in Caucasian and Japanese American women.

Characterization of abdominal and intra-abdominal fat requires imaging, and thus is not feasible in large epidemiologic studies.We investigated whether biomarkers may complement anthropometry (body mass index [BMI], waist circumference [WC], and waist-hip ratio [WHR]) in predicting the size of the body fat compartments by analyzing blood biomarkers, including adipocytokines, insulin resistance markers, sex steroid hormones, lipids, liver enzymes and gastro-neuropeptides.Fasting levels of 58 blood markers were analyzed in 60 healthy, Caucasian or Japanese American postmenopausal women who underwent anthropometric measurements, dual energy X-ray absorptiometry (DXA), and abdominal magnetic resonance imaging. Total, abdominal, visceral and hepatic adiposity were predicted based on anthropometry and the biomarkers using Random Forest models.Total body fat was well predicted by anthropometry alone (R(2) = 0.85), by the 5 best predictors from the biomarker model alone (leptin, leptin-adiponectin ratio [LAR], free estradiol, plasminogen activator inhibitor-1 [PAI1], alanine transaminase [ALT]; R(2) = 0.69), or by combining these 5 biomarkers with anthropometry (R(2) = 0.91). Abdominal adiposity (DXA trunk-to-periphery fat ratio) was better predicted by combining the two types of predictors (R(2) = 0.58) than by anthropometry alone (R(2) = 0.53) or the 5 best biomarkers alone (25(OH)-vitamin D(3), insulin-like growth factor binding protein-1 [IGFBP1], uric acid, soluble leptin receptor [sLEPR], Coenzyme Q10; R(2) = 0.35). Similarly, visceral fat was slightly better predicted by combining the predictors (R(2) = 0.68) than by anthropometry alone (R(2) = 0.65) or the 5 best biomarker predictors alone (leptin, C-reactive protein [CRP], LAR, lycopene, vitamin D(3); R(2) = 0.58). Percent liver fat was predicted better by the 5 best biomarker predictors (insulin, sex hormone binding globulin [SHBG], LAR, alpha-tocopherol, PAI1; R(2) = 0.42) or by combining the predictors (R(2) = 0.44) than by anthropometry alone (R(2) = 0.29).The predictive ability of anthropometry for body fat distribution may be enhanced by measuring a small number of biomarkers. Studies to replicate these data in men and other ethnic groups are warranted

Utility of Self-Rated Adherence for Monitoring Dietary and Physical Activity Compliance and Assessment of Participant Feedback of the Healthy Diet and Lifestyle Study pilot.

We examined the utility of self-rated adherence to dietary and physical activity (PA) prescriptions as a method to monitor intervention compliance and facilitate goal setting during the Healthy Diet and Lifestyle Study (HDLS). In addition, we assessed participants’ feedback of HDLS. HDLS is a randomized pilot intervention that compared the effect of intermittent energy restriction combined with a Mediterranean diet (IER + MED) to a Dietary Approaches to Stop Hypertension (DASH) diet, with matching PA regimens, for reducing visceral adipose tissue area (VAT)

HNF1B and Endometrial Cancer Risk: Results from the PAGE study

We examined the association between HNF1B variants identified in a recent genome-wide association study and endometrial cancer in two large case-control studies nested in prospective cohorts: the Multiethnic Cohort Study (MEC) and the Women's Health Initiative (WHI) as part of the Population Architecture using Genomics and Epidemiology (PAGE) study. A total of 1,357 incident cases of invasive endometrial cancer and 7,609 controls were included in the analysis (MEC: 426 cases/3,854 controls; WHI: 931cases/3,755 controls). The majority of women in the WHI were European American, while the MEC included sizable numbers of African Americans, Japanese and Latinos. We estimated the odds ratios (ORs) per allele and 95% confidence intervals (CIs) of each SNP using unconditional logistic regression adjusting for age, body mass index, and four principal components of ancestry informative markers. The combined ORs were estimated using fixed effect models. Rs4430796 and rs7501939 were associated with endometrial cancer risk in MEC and WHI with no heterogeneity observed across racial/ethnic groups (P≥0.21) or between studies (P≥0.70). The ORper allele was 0.82 (95% CI: 0.75, 0.89; P = 5.63×10−6) for rs4430796 (G allele) and 0.79 (95% CI: 0.73, 0.87; P = 3.77×10−7) for rs7501939 (A allele). The associations with the risk of Type I and Type II tumors were similar (P≥0.19). Adjustment for additional endometrial cancer risk factors such as parity, oral contraceptive use, menopausal hormone use, and smoking status had little effect on the results. In conclusion, HNF1B SNPs are associated with risk of endometrial cancer and that the associated relative risks are similar for Type I and Type II tumors

Aspirin and NSAID use and lung cancer risk: a pooled analysis in the International Lung Cancer Consortium (ILCCO)

Purpose: To investigate the hypothesis that non-steroidal anti-inflammatory drugs (NSAIDs) lower lung cancer risk. Methods: We analysed pooled individual-level data from seven case-control and one cohort study in the International Lung Cancer Consortium (ILCCO). Relative risks for lung cancer associated with self-reported history of aspirin and other NSAID use were estimated within individual studies using logistic regression or proportional hazards models, adjusted for packyears of smoking, age, calendar period, ethnicity and education and were combined using random effects meta-analysis. Results: A total of 4,309 lung cancer cases (mean age at diagnosis 65 years, 45% adenocarcinoma and 22% squamous-cell carcinoma) and 58,301 non-cases/controls were included. Amongst controls, 34% had used NSAIDs in the past (81% of them used aspirin). After adjustment for negative confounding by smoking, ever-NSAID use (affirmative answer to the study-specific question on NSAID use) was associated with a 26% reduction (95% confidence interval 8 to 41%) in lung cancer risk in men, but not in women (3% increase (-11% to 30%)). In men, the association was stronger in current and former smokers, and for squamous-cell carcinoma than for adenocarcinomas, but there was no trend with duration of use. No differences were found in the effects on lung cancer risk of aspirin and non-aspirin NSAIDs. Conclusions Evidence from ILCCO suggests that NSAID use in men confers a modest protection for lung cancer, especially amongst ever-smokers. Additional investigation is needed regarding the possible effects of age, duration, dose and type of NSAID and whether effect modification by smoking status or sex exists