Lifetime number of years of menstruation as a risk index for postmenopausal endometrial cancer in the Norwegian Women and Cancer Study.

INTRODUCTION: Lifetime number of years of menstruation (LNYM) reflects a woman's cumulative exposure to endogenous estrogen and can be used as a measure of the combined effect of reproductive factors related to endometrial cancer (EC) risk. MATERIAL AND METHODS: We aimed to study the association between LNYM and EC risk among postmenopausal women and calculate the population attributable fraction of EC for different LNYM categories. Our study sample consisted of 117 589 women from the Norwegian Women and Cancer (NOWAC) Study. All women were aged 30-70 years at enrollment and completed a baseline questionnaire between 1991 and 2006. Women were followed up for EC to December 2014 through linkages to national registries. We used Cox proportional hazards models to estimate hazard ratios with 95% confidence intervals (95% CIs), adjusted for potential confounders. RESULTS: In all, 720 women developed EC. We found a statistically significant, positive dose-response relationship between LNYM and EC, with a 9.1% higher risk for each additional year of LNYM (P for trend < .001). Using the LNYM category ≥40 as a reference, the hazard ratios for LNYM <25, 25-29, 30-34, 35-39 were 0.17 (95% CI 0.22-0.27), 0.25 (95% CI 0.17-0.36), 0.43 (95% CI 0.32-0.58), and 0.68 (95% CI 0.51-0.92), respectively. The association between LNYM and EC was independent of incomplete pregnancies, menopausal hormone therapy, diabetes, and body mass index. When considering the population attributable fraction, 67% of EC was estimated to be attributable to LNYM ≥25 years. CONCLUSIONS: Our study supports that increasing LNYM is an important and independent predictor of EC risk.

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.

Endometrial cancer risk prediction including serum-based biomarkers: results from the EPIC cohort.

Endometrial cancer risk prediction models including lifestyle, anthropometric and reproductive factors have limited discrimination. Adding biomarker data to these models may improve predictive capacity; to our knowledge, this has not been investigated for endometrial cancer. Using a nested case-control study within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, we investigated the improvement in discrimination gained by adding serum biomarker concentrations to risk estimates derived from an existing risk prediction model based on epidemiologic factors. Serum concentrations of sex steroid hormones, metabolic markers, growth factors, adipokines and cytokines were evaluated in a step-wise backward selection process; biomarkers were retained at p < 0.157 indicating improvement in the Akaike information criterion (AIC). Improvement in discrimination was assessed using the C-statistic for all biomarkers alone, and change in C-statistic from addition of biomarkers to preexisting absolute risk estimates. We used internal validation with bootstrapping (1000-fold) to adjust for over-fitting. Adiponectin, estrone, interleukin-1 receptor antagonist, tumor necrosis factor-alpha and triglycerides were selected into the model. After accounting for over-fitting, discrimination was improved by 2.0 percentage points when all evaluated biomarkers were included and 1.7 percentage points in the model including the selected biomarkers. Models including etiologic markers on independent pathways and genetic markers may further improve discrimination.

High coffee consumption and different brewing methods in relation to postmenopausal endometrial cancer risk in the Norwegian women and cancer study: a population-based prospective study.

BACKGROUND: Coffee and its compounds have been proposed to inhibit endometrial carcinogenesis. Studies in the Norwegian population can be especially interesting due to the high coffee consumption and increasing incidence of endometrial cancer in the country. METHODS: A total of 97 926 postmenopausal Norwegian women from the population-based prospective Norwegian Women and Cancer (NOWAC) Study, were included in the present analysis. We evaluated the general association between total coffee consumption and endometrial cancer risk as well as the possible impact of brewing method. Multivariate Cox regression analysis was used to estimate risks, and heterogeneity tests were performed to compare brewing methods. RESULTS: During an average of 10.9 years of follow-up, 462 incident endometrial cancer cases were identified. After multivariate adjustment, significant risk reduction was found among participants who drank ≥8 cups/day of coffee with a hazard ratio of 0.52 (95% confidence interval, CI 0.34-0.79). However, we did not observe a significant dose-response relationship. No significant heterogeneity in risk was found when comparing filtered and boiled coffee brewing methods. A reduction in endometrial cancer risk was observed in subgroup analyses among participants who drank ≥8 cups/day and had a body mass index ≥25 kg/m2, and in current smokers. CONCLUSIONS: These data suggest that in this population with high coffee consumption, endometrial cancer risk decreases in women consuming ≥8 cups/day, independent of brewing method.

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.

Cigarette smoking and risk of histological subtypes of epithelial ovarian cancer in the EPIC cohort study.

New data regarding a positive association between smoking and risk of epithelial ovarian cancer (EOC), especially the mucinous tumor type, has started to emerge. The purpose of this study was to examine the association between different measures of smoking exposures and subtypes of EOC in a large cohort of women from 10 European countries. The European Prospective Investigation into Cancer and Nutrition (EPIC) cohort is a multicenter prospective study initiated in 1992. The questionnaires included data about dietary, lifestyle, and health factors. Information about cigarette smoking was collected from individuals in all participating countries. We used Cox proportional hazard regression models to estimate hazard ratio (HR) of EOC overall and serous, mucinous, and endometroid histological subtypes, with 95% confidence intervals (CIs) associated with different measures of smoking exposures adjusting for confounding variables. Altogether 836 incident EOC cases were identified among 326,831 women. The tumors were classified as 400 serous, 83 mucinous, 80 endometroid, 35 clear cell, and 238 unspecified. Compared with never smokers, current smokers had a significantly increased risk for mucinous tumors [HR = 1.85 (95% CI 1.08-3.16)] and those smoking more than 10 cigarettes per day had a doubling in risk [HR = 2.25(95% CI 1.26-4.03)] as did those who had smoked less than 15 pack-years of cigarettes [HR = 2.18 (95% CI 1.07-4.43)]. The results from the EPIC study add further evidence that smoking increases risk of mucinous ovarian cancer and support the notion that the effect of smoking varies according to histological subtype.

Menopausal hormone therapy and risk of endometrial carcinoma among postmenopausal women in the European Prospective Investigation Into Cancer and Nutrition.

Estrogen-only menopausal hormone therapy (HT) increases the risk of endometrial cancer, but less is known about the association with other types of HT. Using Cox proportional hazards regression, the authors examined the association of various types of HT with the risk of endometrial cancer among 115,474 postmenopausal women recruited into the European Prospective Investigation into Cancer and Nutrition between 1992 and 2000. After a mean follow-up period of 9 years, 601 incident cases of endometrial cancer were identified. In comparison with never users of HT, risk of endometrial cancer was increased among current users of estrogen-only HT (hazard ratio (HR) = 2.52, 95% confidence interval (CI): 1.77, 3.57), tibolone (HR = 2.96, 95% CI: 1.67, 5.26), and, to a lesser extent, estrogen-plus-progestin HT (HR = 1.41, 95% CI: 1.08, 1.83), although risks differed according to regimen and type of progestin constituent. The association of HT use with risk was stronger among women who were older, leaner, or had ever smoked cigarettes. The finding of a strong increased risk of endometrial cancer with estrogen-only HT and a weaker association with combined HT supports the hypothesis that progestins have an attenuating effect on endometrial cancer risk. The increased risk associated with tibolone use requires further investigation.

Excess Body Weight and Incidence of Type 1 and Type 2 Endometrial Cancer: The Norwegian Women and Cancer Study.

PURPOSE: Excess body weight has been associated with increased risk of 13 cancer types and is a particularly strong risk factor for endometrial cancer (EC). Only a few previous studies have assessed the relationship between excess body weight and EC subtypes. In this study, we aimed to investigate the associations between excess weight and incidence of type 1 and type 2 EC. PATIENTS AND METHODS: We used data from 151,537 participants in the Norwegian Women and Cancer (NOWAC) cohort of which 935 were diagnosed with type 1 and 263 with type 2 EC during follow-up. Height and body weight were self-reported. Multivariable Cox proportional hazard regression was used to assess the associations between body mass index (BMI) and type 1 and type 2 EC. RESULTS: For every 2 kg/m2 increase in BMI, the risk of type 1 EC increased by 21% (HR=1.21, 95% CI: 1.18, 1.24) and the risk of type 2 EC by 10% (HR=1.10, 95% CI: 1.03, 1.16) (pheterogeneity = 0.009). During the period 1991 to 2016, 24.0% (95% CI: 20.0% to 27.8%) of type 1 EC cases was attributable to excess body weight. Avoiding obesity could have prevented 6.6% (95% CI: 3.4% to 9.7%) of type 2 EC cases. CONCLUSION: Excess body weight was associated with both type 1 and type 2 EC in a dose-dependent manner and the association was significantly stronger in type 1 EC. These findings could support the hypothesis that estrogen plays a more important role in the development of type 1 ECs than in type 2 EC.

Coffee and tea consumption and the risk of ovarian cancer: a prospective cohort study and updated meta-analysis.

BACKGROUND: In 2007 the World Cancer Research Fund Report concluded that there was limited and inconsistent evidence for an effect of coffee and tea consumption on the risk of epithelial ovarian cancer (EOC). OBJECTIVE: In the European Prospective Investigation into Cancer and Nutrition (EPIC), we aimed to investigate whether coffee intakes, tea intakes, or both are associated with the risk of EOC. DESIGN: All women participating in the EPIC (n = 330,849) were included in this study. Data on coffee and tea consumption were collected through validated food-frequency questionnaires at baseline. HRs and 95% CIs were estimated by using Cox proportional hazards models. Furthermore, we performed an updated meta-analysis of all previous prospective studies until April 2011 by comparing the highest and lowest coffee- and tea-consumption categories as well as by using dose-response random-effects meta-regression analyses. RESULTS: During a median follow-up of 11.7 y, 1244 women developed EOC. No association was observed between the risk of EOC and coffee consumption [HR: 1.05 (95% CI: 0.75, 1.46) for the top quintile compared with no intake] or tea consumption [HR: 1.07 (95% CI: 0.78, 1.45) for the top quintile compared with no intake]. This lack of association between coffee and tea intake and EOC risk was confirmed by the results of our meta-analysis. CONCLUSION: Epidemiologic studies do not provide sufficient evidence to support an association between coffee and tea consumption and risk of ovarian cancer.

Multiple miscarriages are associated with the risk of ovarian cancer: results from the European Prospective Investigation into Cancer and Nutrition.

While the risk of ovarian cancer clearly reduces with each full-term pregnancy, the effect of incomplete pregnancies is unclear. We investigated whether incomplete pregnancies (miscarriages and induced abortions) are associated with risk of epithelial ovarian cancer. This observational study was carried out in female participants of the European Prospective Investigation into Cancer and Nutrition (EPIC). A total of 274,442 women were followed from 1992 until 2010. The baseline questionnaire elicited information on miscarriages and induced abortions, reproductive history, and lifestyle-related factors. During a median follow-up of 11.5 years, 1,035 women were diagnosed with incident epithelial ovarian cancer. Despite the lack of an overall association (ever vs. never), risk of ovarian cancer was higher among women with multiple incomplete pregnancies (HR(≥4vs.0): 1.74, 95% CI: 1.20-2.70; number of cases in this category: n = 23). This association was particularly evident for multiple miscarriages (HR(≥4vs.0): 1.99, 95% CI: 1.06-3.73; number of cases in this category: n = 10), with no significant association for multiple induced abortions (HR(≥4vs.0): 1.46, 95% CI: 0.68-3.14; number of cases in this category: n = 7). Our findings suggest that multiple miscarriages are associated with an increased risk of epithelial ovarian cancer, possibly through a shared cluster of etiological factors or a common underlying pathology. These findings should be interpreted with caution as this is the first study to show this association and given the small number of cases in the highest exposure categories.