Idlir Licaj

Physical activity and all-cause mortality across levels of overall and abdominal adiposity in European men and women: the European Prospective Investigation into Cancer and Nutrition Study (EPIC)

Background: The higher risk of death resulting from excess adiposity may be attenuated by physical activity (PA). However, the theoretical number of deaths reduced by eliminating physical inactivity compared with overall and abdominal obesity remains unclear. Objective: We examined whether overall and abdominal adiposity modified the association between PA and all-cause mortality and estimated the population attributable fraction (PAF) and the years of life gained for these exposures. Design: This was a cohort study in 334,161 European men and women. The mean follow-up time was 12.4 y, corresponding to 4,154,915 person-years. Height, weight, and waist circumference (WC) were measured in the clinic. PA was assessed with a validated self-report instrument. The combined associations between PA, BMI, and WC with mortality were examined with Cox proportional hazards models, stratified by center and age group, and adjusted for sex, education, smoking, and alcohol intake. Center-specific PAF associated with inactivity, body mass index (BMI; in kg/m2) (>30), and WC (≥102 cm for men, ≥88 cm for women) were calculated and combined in random-effects meta-analysis. Life-tables analyses were used to estimate gains in life expectancy for the exposures. Results: Significant interactions (PA × BMI and PA × WC) were observed, so HRs were estimated within BMI and WC strata. The hazards of all-cause mortality were reduced by 16–30% in moderately inactive individuals compared with those categorized as inactive in different strata of BMI and WC. Avoiding all inactivity would theoretically reduce all-cause mortality by 7.35% (95% CI: 5.88%, 8.83%). Corresponding estimates for avoiding obesity (BMI >30) were 3.66% (95% CI: 2.30%, 5.01%). The estimates for avoiding high WC were similar to those for physical inactivity. Conclusion: The greatest reductions in mortality risk were observed between the 2 lowest activity groups across levels of general and abdominal adiposity, which suggests that efforts to encourage even small increases in activity in inactive individuals may be beneficial to public health.

Lifetime alcohol use and overall and cause-specific mortality in the European Prospective Investigation into Cancer and nutrition (EPIC) study

Objectives To investigate the role of factors that modulate the association between alcohol and mortality, and to provide estimates of absolute risk of death. Design The European Prospective Investigation into Cancer and nutrition (EPIC). Setting 23 centres in 10 countries. Participants 380 395 men and women, free of cancer, diabetes, heart attack or stroke at enrolment, followed up for 12.6 years on average. Main outcome measures 20 453 fatal events, of which 2053 alcohol-related cancers (ARC, including cancers of upper aerodigestive tract, liver, colorectal and female breast), 4187 cardiovascular diseases/coronary heart disease (CVD/CHD), 856 violent deaths and injuries. Lifetime alcohol use was assessed at recruitment. Results HRs comparing extreme drinkers (≥30 g/day in women and ≥60 g/day in men) to moderate drinkers (0.1–4.9 g/day) were 1.27 (95% CI 1.13 to 1.43) in women and 1.53 (1.39 to 1.68) in men. Strong associations were observed for ARC mortality, in men particularly, and for violent deaths and injuries, in men only. No associations were observed for CVD/CHD mortality among drinkers, whereby HRs were higher in never compared to moderate drinkers. Overall mortality seemed to be more strongly related to beer than wine use, particularly in men. The 10-year risks of overall death for women aged 60 years, drinking more than 30 g/day was 5% and 7%, for never and current smokers, respectively. Corresponding figures in men consuming more than 60 g/day were 11% and 18%, in never and current smokers, respectively. In competing risks analyses, mortality due to CVD/CHD was more pronounced than ARC in men, while CVD/CHD and ARC mortality were of similar magnitude in women. Conclusions In this large European cohort, alcohol use was positively associated with overall mortality, ARC and violent death and injuries, but marginally to CVD/CHD. Absolute risks of death observed in EPIC suggest that alcohol is an important determinant of total mortality.

Polymorphisms of Helicobacter pylori signaling pathway genes and gastric cancer risk in the European prospective investigation into cancer-eurgast cohort

Helicobacter pylori is a recognized causal factor of noncardia gastric cancer (GC). Lipopolysaccharide and peptidoglycan of this bacterium are recognized by CD14, TLR4 and NOD2 human proteins, while NFKB1 activates the transcription of pro‐inflammatory cytokines to elicit an immune response. Single nucleotide polymorphisms (SNPs) in these genes have been associated with GC in different populations. We genotyped 30 SNPs of these genes, in 365 gastric adenocarcinomas and 1,284 matched controls from the European Prospective Investigation into Cancer cohort. The association with GC and its histological and anatomical subtypes was analyzed by logistic regression and corrected for multiple comparisons. Using a log‐additive model, we found a significant association between SNPs in CD14, NOD2 and TLR4 with GC risk. However, after applying the multiple comparisons tests only the NOD2 region remained significant (p = 0.009). Analysis according to anatomical subtypes revealed NOD2 and NFKB1 SNPs associated with noncardia GC and CD14 SNPs associated with cardia GC, while analysis according to histological subtypes showed that CD14 was associated with intestinal but not diffuse GC. The multiple comparisons tests confirmed the association of NOD2 with noncardia GC (p = 0.0003) and CD14 with cardia GC (p = 0.01). Haplotype analysis was in agreement with single SNP results for NOD2 and CD14 genes. From these results, we conclude that genetic variation in NOD2 associates with noncardia GC while variation in CD14 is associated with cardia GC.

Coffee and tea consumption, genotype-based CYP1A2 and NAT2 activity and colorectal cancer risk—Results from the EPIC cohort study

Coffee and tea contain numerous antimutagenic and antioxidant components and high levels of caffeine that may protect against colorectal cancer (CRC). We investigated the association between coffee and tea consumption and CRC risk and studied potential effect modification by CYP1A2 and NAT2 genotypes, enzymes involved in the metabolization of caffeine. Data from 477,071 participants (70.2% female) of the European Investigation into Cancer and Nutrition (EPIC) cohort study were analyzed. At baseline (1992–2000) habitual (total, caffeinated and decaffeinated) coffee and tea consumption was assessed with dietary questionnaires. Cox proportional hazards models were used to estimate adjusted hazard ratios (HR) and 95% confidence intervals (95% CI). Potential effect modification by genotype‐based CYP1A2 and NAT2 activity was studied in a nested case–control set of 1,252 cases and 2,175 controls. After a median follow‐up of 11.6 years, 4,234 participants developed CRC (mean age 64.7 ± 8.3 years). Total coffee consumption (high vs. non/low) was not associated with CRC risk (HR 1.06, 95% CI 0.95–1.18) or subsite cancers, and no significant associations were found for caffeinated (HR 1.10, 95% CI 0.97–1.26) and decaffeinated coffee (HR 0.96, 95% CI 0.84–1.11) and tea (HR 0.97, 95% CI 0.86–1.09). High coffee and tea consuming subjects with slow CYP1A2 or NAT2 activity had a similar CRC risk compared to non/low coffee and tea consuming subjects with a fast CYP1A2 or NAT2 activity, which suggests that caffeine metabolism does not affect the link between coffee and tea consumption and CRC risk. This study shows that coffee and tea consumption is not likely to be associated with overall CRC.

Intake of Coffee, Decaffeinated Coffee, or Tea Does Not Affect Risk for Pancreatic Cancer: Results From the European Prospective Investigation into Nutrition and Cancer Study

BACKGROUND & AIMS Few modifiable risk factors have been implicated in the etiology of pancreatic cancer. There is little evidence for the effects of caffeinated coffee, decaffeinated coffee, or tea intake on risk of pancreatic cancer. We investigated the association of total coffee, caffeinated coffee, decaffeinated coffee, and tea consumption with risk of pancreatic cancer. METHODS This study was conducted within the European Prospective Investigation into Nutrition and Cancer cohort, comprising male and female participants from 10 European countries. Between 1992 and 2000, there were 477,312 participants without cancer who completed a dietary questionnaire and were followed up to determine pancreatic cancer incidence. Coffee and tea intake was calibrated with a 24-hour dietary recall. Adjusted hazard ratios (HRs) were computed using multivariable Cox regression. RESULTS During a mean follow-up period of 11.6 y, 865 first incidences of pancreatic cancers were reported. When divided into fourths, neither total intake of coffee (HR, 1.03; 95% confidence interval [CI], 0.83-1.27; high vs low intake), decaffeinated coffee (HR, 1.12; 95% CI, 0.76-1.63; high vs low intake), nor tea were associated with risk of pancreatic cancer (HR, 1.22, 95% CI, 0.95-1.56; high vs low intake). Moderately low intake of caffeinated coffee was associated with an increased risk of pancreatic cancer (HR, 1.33; 95% CI, 1.02-1.74), compared with low intake. However, no graded dose response was observed, and the association attenuated after restriction to histologically confirmed pancreatic cancers. CONCLUSIONS Based on an analysis of data from the European Prospective Investigation into Nutrition and Cancer cohort, total coffee, decaffeinated coffee, and tea consumption are not related to the risk of pancreatic cancer.

Physical activity and risk of endometrial cancer in the Norwegian Women and Cancer (NOWAC) study

Few studies have investigated the association between endometrial cancer and physical activity (PA) using repeated measures of PA and different subtypes of endometrial cancer. We aimed to investigate the association between endometrial cancer and PA level at two points in time in women with different body mass index (BMI) profiles, and to calculate the population attributable fraction (PAF) of endometrial cancer for low PA levels. We included 82,759 women with complete information on PA at baseline in the Norwegian Women and Cancer Study; 52,370 had follow‐up information on PA. 687 endometrial cancer cases were identified. Multivariate cox proportional hazard models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI). The PAF indicated the proportion of endometrial cancer that could be avoided in the population if these women had a higher PA level. There was a statistically significant association between low PA levels at baseline and follow‐up and endometrial cancer risk, with a dose‐response trend (lowest PA level: HR = 1.60, 95% CI 1.16–2.20; highest PA level: HR = 0.73, 95% CI 0.45–1.16 compared to the median). Analyses that included follow‐up measurements yielded similar results. 21.9% (95% CI 7.1–34.3) of endometrial cancers could be avoided if women with low PA levels (≤ 4 in a 1–10 degree self reported PA scale) increased their PA levels to 5‐10. We found an inverse dose‐response association between PA and endometrial cancer, independent of BMI. In this nationally representative cohort, 21.9% of endometrial cancers could potentially be avoided if PA levels increased to higher PA levels.

Smoking and risk of ovarian cancer by histological subtypes: an analysis among 300 000 Norwegian women.

Background:We prospectively investigated the association between different measures of smoking exposure and the risk of serous, mucinous, and endometrioid ovarian cancers (OC) in a cohort of more than 300 000 Norwegian women.Methods:We followed 300 398 women aged 19–67 years at enrolment until 31 December 2013 for OC incidence through linkage to national registries. We used Cox proportional hazards models with attained age as the underlying time scale to estimate multivariable-adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) adjusted for relevant confounders.Results:During more than 5.9 million person-years and a median follow-up time of 19 years, 2336 primary invasive (1647, 71%) and borderline (689, 29%) OC were identified (53% serous, 19% mucinous). Compared with never smokers, current smokers who had smoked for ⩾10 years had a higher risk of mucinous OC (HR10–19 years vs never=1.73, 95% CI 1.24–2.42; HR⩾20 vs never=2.26, 95% CI 1.77–2.89, Ptrend <0.001). When stratified by invasiveness, current smokers had a higher risk of invasive mucinous OC (HR=1.78, 95% CI 1.20–2.64) and borderline mucinous OC (HR=2.26 95% CI, 1.71–2.97) (Pheterogeneity=0.34) than never smokers. Smoking was not associated with serous or endometrioid OC.Conclusions:Using a very large cohort of women, the current analysis provides an important replication for a similar risk of invasive and borderline mucinous OC related to smoking.

Epithelial ovarian cancer subtypes attributable to smoking in the Norwegian Women and Cancer Study, 2012

Among European women, ovarian cancer is the fifth most common cancer. Smoking is an established risk factor for mucinous tumors. We estimated the impact of smoking in Norwegian women using population attributable fractions (PAFs) of epithelial ovarian cancer (EOC), by invasiveness and by histological subtypes in the Norwegian Women and Cancer Study with an average of 13.2 years of follow‐up. During >2 million person‐years, a total of 915 incident EOC cases, of which 667 (73%) invasive and 248 (27%) borderline, were identified among 154,234 women aged 34–70 years at enrolment. Compared with never smokers, current smokers had a nonstatistically significant increased risk of mucinous tumors (hazard ratio [HR] = 1.67 [95% confidence interval, (CI), 0.96–2.96]) and more than twice statistically significant risk of borderline mucinous tumors (HR = 2.17 [95% CI, 1.06–4.45]). The corresponding PAF estimates were 16.5% for mucinous and 25% for borderline mucinous. We found that among middle‐aged women, one in six mucinous tumors and one in four borderline mucinous tumors could have been prevented if women did not smoke.

Polymorphisms of H. pylori signaling pathway genes and gastric cancer risk in the European EPIC-eurgast cohort

Helicobacter pylori is a recognized causal factor of noncardia gastric cancer (GC). Lipopolysaccharide and peptidoglycan of this bacterium are recognized by CD14, TLR4 and NOD2 human proteins, while NFKB1 activates the transcription of pro‐inflammatory cytokines to elicit an immune response. Single nucleotide polymorphisms (SNPs) in these genes have been associated with GC in different populations. We genotyped 30 SNPs of these genes, in 365 gastric adenocarcinomas and 1,284 matched controls from the European Prospective Investigation into Cancer cohort. The association with GC and its histological and anatomical subtypes was analyzed by logistic regression and corrected for multiple comparisons. Using a log‐additive model, we found a significant association between SNPs in CD14, NOD2 and TLR4 with GC risk. However, after applying the multiple comparisons tests only the NOD2 region remained significant (p = 0.009). Analysis according to anatomical subtypes revealed NOD2 and NFKB1 SNPs associated with noncardia GC and CD14 SNPs associated with cardia GC, while analysis according to histological subtypes showed that CD14 was associated with intestinal but not diffuse GC. The multiple comparisons tests confirmed the association of NOD2 with noncardia GC (p = 0.0003) and CD14 with cardia GC (p = 0.01). Haplotype analysis was in agreement with single SNP results for NOD2 and CD14 genes. From these results, we conclude that genetic variation in NOD2 associates with noncardia GC while variation in CD14 is associated with cardia GC.

Coffee Drinking and the Risk of Endometrial Cancer: An Updated Meta-Analysis of Observational Studies

ABSTRACT Background: Several compounds contained in coffee have been found to suppress carcinogenesis in experimental studies. We conducted a dose–response meta-analysis to assess the impact of coffee consumption on the risk of endometrial cancer. Materials and methods: We searched MEDLINE and EMBASE databases for studies published up to August 2016. Using random effects models, we estimated summary relative risks (RR) for cohort studies and odds ratios (OR) for case-control studies with 95% confidence intervals (CI). Dose–response analyses were conducted by using generalized least square trend estimation. Results: We identified 12 cohort studies and 8 case-control studies eligible for inclusion, contributing with 11,663 and 2,746 endometrial cancer cases, respectively. The summary RR for highest compared with lowest coffee intake was 0.74 (95% CI: 0.68–0.81; pheterogeneity = 0.09, I2 = 32%). The corresponding summary RR among cohort studies was 0.78 (95% CI: 0.71–0.85; pheterogeneity = 0.14, I2 = 31.9%) and 0.63 (95% CI: 0.53–0.76; pheterogeneity = 0.57, I2 = 0%) for case-control studies. One-cup increment per day was associated with 3% risk reduction (95% CI: 2–4%) in cohort studies and 12% (95% CI: 5–18%) in case-control studies. After pooling the results from 5 cohort studies, the association remained significant only in women with body mass index over 30 (RR = 0.71, 95% CI: 0.61–0.81). Conclusion: The results from our meta-analysis strengthen the evidence of a protective effect of coffee consumption on the risk of EC and further suggest that increased coffee intake might be particularly beneficial for women with obesity.