A prospective investigation of coffee drinking and endometrial cancer incidence

Coffee drinking may be associated with reduced risk of endometrial cancer; however, prospective data are limited. Further, it is not clear whether any association between coffee and endometrial cancer differs according to coffee caffeine content. The association of coffee drinking with incidence of endometrial cancer was evaluated among 226,732 women, aged 50-71, enrolled in the NIH-AARP Diet and Health Study who completed a baseline epidemiologic questionnaire. Following a mean 9.3 years of follow-up, data were available for 1,486 incident endometrial cancer cases. Cox proportional hazards models were used to estimate associations of coffee with endometrial cancer incidence. Sub-group analyses were performed according to smoking status, hormone therapy use (HT) and body habitus. Coffee drinking was inversely related to incidence of endometrial cancer (hazard ratio [HR] comparing drinking of >3 cups/day versus no cups = 0.64, 95% CI, 0.51-0.80; P(trend) = 0.0004). The association of coffee with endometrial cancer risk was apparent for consumption of both regular (HR per cup = 0.90, 95% CI, 0.86-0.95) and decaffeinated coffee (HR per cup = 0.93, 95% CI, 0.87-0.99). The relation of coffee with endometrial cancer incidence varied significantly by HT use (P(interaction) = 0.03) with an association only apparent among HT-never users (HR comparing drinking >3 cups/day versus no cups = 0.54, 95% CI, 0.41-0.72; P(trend) = 0.0005). Endometrial cancer incidence appears to be reduced among women that habitually drink coffee, an association that does not differ according to caffeine content.     

No effect of meat,meat cooking preferences,meat mutagens or heme iron on lung cancer risk in the prostate,lung, colorectal and ovarian cancer screening trial

Recent epidemiological studies have suggested that red and processed meat may increase the risk of lung cancer. Possible underlying mechanisms include mutagens produced during high‐temperature cooking or preservation, or formed endogenously from heme iron in meat. We used data from 99,579 participants of both screened and nonscreened arms of the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial, aged 55–74 years, to investigate whether meat type, cooking method, doneness level, intake of specific meat mutagens 2‐amino‐3,8‐dimethylimidazo[4,5‐f]quinoxaline (MeIQx), 2‐amino‐3,4,8‐trimethylimidazo[4,5‐f]quinoxaline] (DiMeIQx), 2‐amino‐1‐methyl‐6‐phenylimidazo[4,5‐b]pyridine (PhIP) and benzo(a)pyrene (B(a)P)] and heme iron are associated with lung cancer. Participants' diet was assessed prospectively using a 124‐item food frequency questionnaire and an additional meat‐cooking module. Dietary data were used in conjunction with a database to estimate intake of MeIQx, DiMeIQx, PhIP, B(a)P and heme iron. After up to 8 years of follow‐up, 782 incident lung cancer cases were ascertained. Lung cancer risk was not associated with the consumption of either red (men: HR_{Q5 vs. Q1} = 1.11, 95% CI = 0.79–1.56, P_trend = 0.42; women: HR_{Q5 vs. Q1} = 1.30, 95% CI = 0.87–1.95, P_trend = 0.65) or processed meat (men: HR_{Q5 vs. Q1} = 1.12, 95% CI = 0.83–1.53, P_trend = 0.22; women: HR_{Q5 vs. Q1} = 0.98, 95% CI = 0.68–1.41, P_trend = 0.32) in multivariable models. High‐temperature cooking methods, level of meat doneness, meat mutagens and heme iron had no effect on lung cancer risk. In this population, we found no association between meat type, cooking method, doneness level or intake of specific meat mutagens or heme iron and lung cancer risk.     

Physical activity and risk of endometrial cancer: the European prospective investigation into cancer and nutrition

The etiologic role of physical activity in endometrial cancer risk remains unclear given the few epidemiologic studies that have been conducted. To investigate this relation more fully, an analysis was undertaken in the European prospective investigation into cancer and nutrition (EPIC). During an average 6.6 years of follow-up, 689 incident endometrial cancer cases were identified from an analytic cohort within EPIC of 253,023 women. Cox proportional hazards models were used to estimate the associations between type of activity (total, occupational, household, recreational) and endometrial cancer risk. For total activity, women in the highest compared with the lowest quartile of activity had a risk of 0.88 (95% confidence interval (95% CI=0.61-1.27). No clear associations between each type of activity and endometrial cancer risk were found for the total study population combined. Associations were more evident in the stratified results, with premenopausal women who were active versus inactive experiencing a risk of 0.66 (95% CI=0.38-1.14) overall. Among premenopausal women, for household and recreational activities the risk estimates in the highest as compared with the lowest quartiles were, respectively, 0.48 (95% CI=0.23-0.99) and 0.78 (95% CI=0.44-1.39). No effect modification by body mass index, hormone replacement therapy, oral contraceptive use or energy intake was found. This study provides no evidence of a protective effect of increased physical activity in endometrial cancer risk in all women but some support for a benefit among premenopausal women. The relative risk reductions are most apparent for household activities.     

Physical activity,sedentary behaviours,and the prevention of endometrial cancer

Physical activity has been hypothesised to reduce endometrial cancer risk, but this relationship has been difficult to confirm because of a limited number of prospective studies. However, recent publications from five cohort studies, which together comprise 2663 out of 3463 cases in the published literature for analyses of recreational physical activity, may help resolve this question. To synthesise these new data, we conducted a meta-analysis of prospective studies published through to December 2009. We found that physical activity was clearly associated with reduced risk of endometrial cancer, with active women having an approximately 30% lower risk than inactive women. Owing to recent interest in sedentary behaviour, we further investigated sitting time in relation to endometrial cancer risk using data from the NIH-AARP Diet and Health Study. We found that, independent of the level of moderate–vigorous physical activity, greater sitting time was associated with increased endometrial cancer risk. Thus, limiting time in sedentary behaviours may complement increasing level of moderate–vigorous physical activity as a means of reducing endometrial cancer risk. Taken together with the established biological plausibility of this relation, the totality of evidence now convincingly indicates that physical activity prevents or reduces risk of endometrial cancer.     

Meat, fish, poultry and egg consumption in relation to risk of pancreatic cancer: a prospective study

High meat consumption has been associated with increased risk of pancreatic cancer in several, although not all, case-control studies. However, prospective data on this relationship are sparse, and the results have been inconsistent. We prospectively evaluated meat, fish, poultry, and egg consumption in relation to pancreatic cancer incidence in a population-based cohort of 61,433 Swedish women. Diet was assessed with a food-frequency questionnaire at baseline (1987-1990) and again in 1997. Pancreatic cancers were ascertained through linkage to the Swedish Cancer Register. Cox proportional hazards models were used to estimate multivariate hazard ratios with 95% confidence intervals (CI). During the 941,218 person-years of follow-up, from 1987 through 2004, 172 incident cases of pancreatic cancer were diagnosed. Long-term red meat consumption (using data from both dietary questionnaires) was positively associated with risk of pancreatic cancer (p-trend = 0.01), whereas long-term poultry consumption was inversely (p-trend = 0.04) associated with risk. The multivariate hazard ratios for the highest versus the lowest category of consumption were 1.73 (95% CI = 0.99-2.98) for red meat and 0.44 (95% CI = 0.20-0.97) for poultry. There were no significant associations with processed meat, fish or egg consumption. Findings from this prospective study suggest that substituting poultry for red meat might reduce the risk of pancreatic cancer.     

Intake of meat, meat mutagens, and iron and the risk of breast cancer in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial

Background:

Epidemiological evidence on meat intake and breast cancer is inconsistent, with little research on potentially carcinogenic meat-related exposures. We investigated meat subtypes, cooking practices, meat mutagens, iron, and subsequent breast cancer risk.

Methods:

Among 52 158 women (aged 55–74 years) in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, who completed a food frequency questionnaire, 1205 invasive breast cancer cases were identified. We estimated meat mutagen and haem iron intake with databases accounting for cooking practices. Using Cox proportional hazards regression, we calculated hazard ratios (HRs) and 95% confidence intervals (CIs) within quintiles of intake.

Results:

Comparing the fifth to the first quintile, red meat (HR=1.23; 95% CI=1.00–1.51, P trend=0.22), the heterocyclic amine (HCA), 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), (HR=1.26; 95% CI=1.03–1.55; P trend=0.12), and dietary iron (HR=1.25; 95% CI=1.02–1.52; P trend=0.03) were positively associated with breast cancer. We observed elevated, though not statistically significant, risks with processed meat, the HCA 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (DiMeIQx), mutagenic activity, iron from meat, and haem iron from meat.

Conclusion:

In this prospective study, red meat, MeIQx, and dietary iron elevated the risk of invasive breast cancer, but there was no linear trend in the association except for dietary iron.     

Nutrition and endometrial cancer

Epidemiologic evidence on the relation between nutrition and endometrial cancer (EC) is reviewed. Obesity is an important determinant of EC, probably because of its effect on the hormonal milieu of both pre-and postmenopausal women. However, epidemiologic studies of body fat distribution and EC are inconsistent, as are the data pertaining to the relation between body fat distribution and sex hormones. Randomized and observational studies of diet and sex hormones indicate that low fat diets may be associated weakly with decreased estrogen levels, and thus a lowering of EC risk. Only ecologic and case-control studies of diet and EC have been reported. These finding as well as the methodologic limitations of these study designs are discussed. Both types of studies implicate fat as a potential risk factor, while the case-control studies suggest that carotene may lower risk of EC. Epidemiologic studies of alcohol and EC also are inconsistent, but generally indicate no association, or a weak protective effect. The role of diet in the etiology of EC is unresolved. The conduct of cohort and intervention studies, which can avoid many of the methodologic shortcomings of ecologic and case-control studies, would improve our understanding of diet and EC.Address correspondence to Dr Hill.     

Breastfeeding and the incidence of endometrial cancer: A meta-analysis

Several epidemiological studies have investigated the association between breastfeeding and endometrial cancer (EC). However, the results of the studies are controversial. Thus, we conduct this meta-analysis to explore the association between breastfeeding and EC and to evaluate the possible does-response relationship between duration of breastfeeding and EC. PubMed, Web of Science, Chinese National Knowledge Infrastructure, China biology medical literature database, Wan fang databases and Database of Chinese Scientific and Technical Periodicals were searched for eligible observational studies up to 11 July 2015. Random effects model was used to calculate the pooled relative risks (RRs) and restricted cubic spline model was adopted for the does-response analysis.Fifteen articles with 623570 participants were identified. The RRs of these studies suggested that breastfeeding was associated with the reduced risk of EC (high versus low/no: RR = 0.74; 95% confidence interval (CI), 0.58–0.95). In subgroup analyses, a significant association of breastfeeding with EC risk was found in Asia (RR = 0.57, 95% CI 0.37–0.87), and an inverse association of breastfeeding with EC risk was found in cohort studies (RR = 0.62, 95% CI 0.41–0.94). The results were also significant after adjusted for hormone use (RR = 0.63, 95% CI 0.41–0.97) and body mass index (RR=0.65, 95% CI 0.44–0.96). A linear relationship was found of breastfeeding with EC (p for nonlinearity = 0.93), and it indicated that EC risk decreased by 1.2% for one month increment of breastfeeding. This meta-analysis indicates that long term breastfeeding might be associated with decreased risk of EC.     

Long‐term dietary acrylamide intake and risk of endometrial cancer in a prospective cohort of Swedish women

Acrylamide has been found in foods heated at high temperatures and there is evidence of carcinogenicity of acrylamide in experimental animals. However, the potential health risks of dietary acrylamide intake in humans remain uncertain. We examined the association between dietary acrylamide intake and the incidence of endometrial cancer among 61,226 participants of the Swedish Mammography Cohort who were cancer‐free at enrollment in 1987–1990 and completed a food frequency questionnaire at baseline and again in 1997. Cox proportional hazards models were used to estimate rate ratios with 95% confidence intervals, adjusted for endometrial cancer risk factors. During a mean follow‐up of 17.7 years, a total of 687 incident cases of endometrial adenocarcinoma were diagnosed in the cohort. We found no association between long‐term acrylamide intake and risk of endometrial cancer. The multivariate rate ratio of endometrial cancer for women in the highest quartile of acrylamide intake (mean, 33.8 μg/day) compared to those in the lowest quartile (mean, 15.9 μg/day) was 0.96 (95% CI, 0.76–1.21). The association did not vary materially by smoking status. In conclusion, these findings do not support the hypothesis that dietary acrylamide intake is positively associated with risk of endometrial cancer, at least not within the ranges of acrylamide consumed in this population. © 2008 Wiley‐Liss, Inc.     

Body mass, diabetes and smoking, and endometrial cancer risk: a follow-up study

We examined the relationship of body mass index (BMI), diabetes and smoking to endometrial cancer risk in a cohort of 36 761 Norwegian women during 15.7 years of follow-up. In multivariable analyses of 222 incident cases of endometrial cancer, identified by linkage to the Norwegian Cancer Registry, there was a strong increase in risk with increasing BMI (P-trend <0.001). Compared to the reference (BMI 20-24 kg m(-2)), the adjusted relative risk (RR) was 0.53 (95% confidence interval (CI): 0.19-1.47) for BMI<20 kg m(-2), 4.28 (95% CI: 2.58-7.09) for BMI of 35-39 kg m(-2) and 6.36 (95% CI: 3.08-13.16) for BMI>or=40 kg m(-2). Women with known diabetes at baseline were at three-fold higher risk (RR 3.13, 95% CI: 1.92-5.11) than those without diabetes; women who reported current smoking at baseline were at reduced risk compared to never smokers (RR 0.55, 95% CI: 0.35-0.86). The strong linear positive association of BMI with endometrial cancer risk and a strongly increased risk among women with diabetes suggest that any increase in body mass in the female population will increase endometrial cancer incidence.     

Risk of endometrial cancer for women diagnosed with HNPCC‐related colorectal carcinoma

The risk of endometrial cancer (EC) subsequent to a diagnosis of colorectal cancer in women with a germline mutation in a mismatch repair gene [Lynch syndrome or hereditary non‐polyposis colon cancer (HNPCC)] is unknown. We estimated the risk of EC following a diagnosis of colorectal carcinoma (CRC) for women with Lynch syndrome. A retrospective cohort study was performed on women diagnosed with CRC with a germline mutation in a mismatch repair (MMR) gene (Lynch syndrome cases), and women with microsatellite stable (MSS) CRC who were not known to carry a germline mutation (non‐Lynch cases), identified from the Colon Cancer Family Registry. The incidence of EC following CRC was estimated and compared for women with and without Lynch syndrome, using adjusted hazards ratios calculated for time at risk among each group. A total of 112 women with Lynch syndrome and a previous diagnosis of CRC were compared with 908 women without Lynch and with a MSS CRC diagnosis. The estimated 10‐year cumulative risk of EC subsequent to CRC was 23.4% [95% confidence interval (CI): 15–36%] for Lynch syndrome women compared with 1.6% (95% CI: 0.7–3.8%) for non‐Lynch women. After adjusting for ascertainment, age at diagnosis and diagnosis of other cancers, risk of subsequent diagnosis with EC was elevated sixfold in women with Lynch syndrome compared with non‐Lynch women (HR 6.2; 95% CI 2.2–17.3; p = 0.001). Approximately one quarter of women diagnosed with Lynch syndrome‐associated CRC developed EC within 10 years. This supports the sentinel cancer concept and suggests that active and early management is important for these women.     

Longitudinal study on birthweight and the incidence of endometrial cancer

From 1976 to 2004, we followed 71,751 participants of the Nurses' Health Study and identified 676 invasive endometrial cancer cases. Birthweight, assessed in 1992, was not associated with the incidence of endometrial cancer. No effect modification by menopausal status was observed, but statistical power to detect an interaction was limited.     

Alcohol intake and endometrial cancer risk: a meta-analysis of prospective studies

Background:

Studies on alcohol intake in relation to endometrial cancer risk have produced inconsistent results.

Methods:

For a meta-analysis, we identified cohort studies of alcohol and endometrial cancer by a literature search of Pub-Med and Embase up to 1 March 2010 and by searching the reference lists of relevant articles.

Results:

Seven cohort studies, including 1 511 661 participants and 6086 endometrial cancer cases, were included in the dose–response random-effect meta-regression model. Compared with non-drinkers, women drinking less than 1 drink of alcohol (13 g of ethanol) per day had a lower risk for endometrial cancer; this risk was lower by 4% (95% confidence interval (95% CI): 0.93–1.00) for consumption up to 0.5 drink per day and by 7% (95% CI: 0.85–1.02) for consumption up to 1 drink. However, we found evidence of an increased risk for endometrial cancer for intakes higher than two alcoholic drinks per day: compared with non-drinkers, the risk was higher by 14% (95% CI: 0.95–1.36) for 2–2.5 drinks per day and by 25% (95% CI: 0.98–1.58) for >2.5 drinks per day.

Conclusion:

Our meta-analysis indicates a possible J-shaped relationship between alcohol intake and endometrial cancer risk.     

Risk for endometrial cancer following breast cancer: a prospective study in Sweden

The risk for endometrial cancer among women with breast cancer might increase following use of tamoxifen, recently classified as a carcinogen of the human endometrium. However, the strength of the association remains uncertain and it is unknown whether use of this drug - widely prescribed in Sweden since the mid-1980s - has had any measurable effect at the population level. We analyzed all cases of breast cancer (n = 131,614) detected in the nationwide Swedish Cancer Registry in 1958-93. Incident cases of endometrial cancer during follow-up were identified also through the Cancer Registry. Standardized incidence ratios (SIR) and their 95 percent confidence intervals(CI) were computed by use of nationwide rates of endometrial cancer, adjusted for age and calendar year. During follow-up of up to 35 years of the breast cancer cohort, 803 incident endometrial cancers were identified, yielding an overall SIR of 1.58 (CI = 1.47-1.70). In univariate analyses, there was no increase in SIR in recent years. However, the excess risk increased linearly with increasing age at breast cancer diagnosis (P trend < 0.0001) and decreased markedly with longer follow-up (P trend < 0.0001). A multivariate regression analysis, with adjustment for age and year of follow-up, revealed no increased risk for subsequent endometrial cancer among breast cancer cases diagnosed more recently (P trend = 0.19); compared with the period 1958-63,the risk estimate in the last time period (1989-93) was 0.72 (CI =0.51-1.01). We conclude that the risk for endometrial cancer following breast cancer has not increased over time in Sweden. This revised version was published online in July 2006 with corrections to the Cover Date.     

Assessment of endometrial sampling as a predictor of final surgical pathology in endometrial cancer

Background:

The histology and grade of endometrial cancer are important predictors of disease outcome and of the likelihood of nodal involvement. In most centres, however, surgical staging decisions are based on a preoperative biopsy. The objective of this study was to assess the concordance between the preoperative histology and that of the hysterectomy specimen in endometrial cancer.

Methods:

Patients treated for endometrial cancer during a 10-year period at a tertiary cancer centre were identified from a prospectively collected pathological database. All pathology reports were reviewed to confirm centralised reporting of the original sampling or biopsy specimens; patients whose biopsies were not reviewed by a dedicated gynaecological pathologist at the treating centre were excluded. Surgical pathology data including histology, grade, depth of myometrial invasion, cervical stromal involvement and lymphovascular space invasion (LVSI) as well as preoperative histology and grade were collected. Preoperative and final tumour cell type and grade were compared and the distribution of other high-risk features was analysed.

Results:

A total of 1329 consecutive patients were identified; 653 patients had a centrally reviewed epithelial endometrial cancer on their original biopsy, and are included in this study. Of 255 patients whose biopsies were read as grade 1 (G1) adenocarcinoma, 45 (18%) were upgraded to grade 2 (G2) on final pathology, 6 (2%) were upgraded to grade 3 (G3) and 5 (2%) were read as a non-endometrioid high-grade histology. Overall, of 255 tumours classified as G1 endometrioid cancers on biopsy, 74 (29%) were either found to be low-grade (G1–2) tumours with deep myometrial invasion, or were reclassified as high-grade cancers (G3 or non-endometrioid histologies) on final surgical pathology. Despite these shifts, we calculate that omitting surgical staging in preoperatively diagnosed G1 endometrioid cancers without deep myometrial invasion would result in missing nodal involvement in only 1% of cases.

Conclusions:

Preoperative endometrial sampling is only a modest predictor of surgical pathology features in endometrial cancer and may underestimate the risk of disease spread and recurrence. In spite of frequent shifts in postoperative vs preoperative histological assessment, the predicted rate of missed nodal metastases with a selective staging policy remains low.     

Dietary fatty acids intake and endometrial cancer risk: a dose-response meta-analysis of epidemiological studies

Epidemiological studies have provided controversial evidence of the association between dietary fatty acids intake and endometrial cancer risk. The continuous update project of World Cancer Research Fund failed to focus on this issue. To address this inconsistency, we conducted this dose-response meta-analysis based on epidemiological studies published up to the end of June 2015 identified from PubMed, EMBASE and Web of Science. Two authors independently performed the eligibility evaluation and data extraction. Random-effects models were used to estimate summary relative risks (RRs) and 95% confidence intervals (CIs). Fourteen epidemiological studies (4 cohort and 10 case-control studies) were included in this dose-response meta-analysis. The summary RR for an intake increment of 10g/day was 1.02 (95% CI = 0.97–1.08; I² = 66.0%) for saturated fatty acids, 0.98 (95% CI = 0.96–1.001; I² = 0%) for monounsaturated fatty acids, and 1.00 (95% CI = 0.95–1.06; I² = 0%) for polyunsaturated fatty acids intake. Non-significant results were observed in the majority of subgroup analyses stratified by study characteristics and adjustment for potential confounders in analyses of aforementioned associations. In conclusion, results from this dose-response meta-analysis provided limited evidence that dietary saturated, monounsaturated, and polyunsaturated fatty acids consumption was associated with endometrial cancer risk. Further studies, especial prospective designed or pooled studies are warranted to confirm our findings.     

Serum lipids and endometrial cancer risk: Results from the HUNT‐II study

Obesity is a major risk factor for endometrial cancer. Still, the association of obesity‐related metabolic factors, such as serum lipids and lipoprotein levels, is unclear. We prospectively examined the association of serum levels of triglycerides, total cholesterol, low‐density lipoprotein cholesterol, non–high‐density lipoprotein (non‐HDL), and HDL cholesterol with endometrial cancer risk among 31,473 women. During 9 years of follow‐up, 100 cases of endometrial cancer were identified by linkage to the Cancer Registry of Norway. There was a positive association of serum triglyceride levels with endometrial cancer risk. Comparing the highest to the lowest quartile of triglycerides, the age‐adjusted hazard ratio was 2.34 (95% CI: 1.04–5.28), and further adjustment for body mass index attenuated the association (hazard ratio 1.79, 95% CI: 0.79–4.05). For total serum cholesterol, low‐density lipoprotein cholesterol and HDL cholesterol there were no associations with endometrial cancer risk, either without or after adjustment for body mass index. Serum triglyceride levels were positively associated with the risk of endometrial cancer, and some of the association seems to be attributable to obesity. Apart from higher estrogen levels produced in adipose tissue, mechanisms more specifically related to triglycerides may also be involved in endometrial cancer. Further prospective studies on this subject are needed to better understand the association of blood lipids with endometrial cancer risk. © 2009 UICC