Smoking and the risk of endometrial cancer: results from the Nurses' Health Study

An inverse association between smoking and endometrial cancer has generally been observed, primarily among current smokers. To assess this association, we analyzed data from the prospective Nurses' Health Study. From 1976 to 2000, 702 cases of invasive endometrial cancer were identified during 1.8 million person-years of follow-up. Smoking status was assessed in 1976 and updated every 2 years. Cox proportional hazards models were used to calculate multivariate relative risks (RRs), controlling for endometrial cancer risk factors. Compared to never smokers, the multivariate RR of endometrial cancer was significantly lower among both current smokers (RR = 0.63; 95% CI = 0.50-0.79) and past smokers (RR = 0.73; 95% CI = 0.62-0.87). When additionally adjusting for body mass index (BMI), the RR for current smokers was attenuated (RR = 0.72; 95% CI = 0.57-0.90), but the RR for past smokers did not change. Risk was lower among women who smoked 35 or more cigarettes a day (RR = 0.60; 95% CI = 0.39-0.91) and among those who smoked for 40 or more years (RR = 0.63; 95% CI = 0.45-0.87). Tests for trend, which excluded never smokers, were not statistically significant for any of the smoking variables analyzed. These data indicate that both current and past smoking are associated with a lower risk of endometrial cancer. The findings provide insight into disease etiology and suggest that the influence of smoking on endometrial cancer risk occurs even in early adulthood, is long-lasting, and may not be attributed solely to short-term hormonal modulation.     

A prospective cohort study of cigarette smoking and the risk of endometrial cancer

Case-control studies have shown inverse associations between cigarette smoking and endometrial cancer risk. However, two small prospective cohort studies have not clearly supported an association. Moreover, quantitative measures of smoking have been examined infrequently. Our aim was to study the association between smoking and endometrial cancer risk in a large prospective cohort. We used proportional hazards models to estimate hazard ratios relating cigarette smoking to endometrial cancer risk among 70 591 women aged 40-59 years at recruitment into a randomised controlled trial of mammography screening for breast cancer. During an average of 10.6 years of follow-up (751 833 person-years), a total of 403 women were diagnosed with incident endometrial cancer. We found that a reduced endometrial cancer risk was evident only among women who currently smoked 20 cigarettes per day or more (hazard ratio=0.62, 95% CI=0.42-0.92, P for trend=0.03). There was some suggestion of an inverse association with smoking duration, but this was less clear. The association did not vary with menopausal status, relative body weight, or the use of hormone replacement therapy, but it appeared to be stronger among parous than nulliparous women. The underlying biological mechanisms of this association remain unclear.     

The role of body weight in the relationship between physical activity and endometrial cancer: results from a large cohort of US women

Factors influencing circulating estrogen levels, insulin-mediated pathways or energy balance through obesity-related mechanisms, such as physical activity, have been proposed as potential risk factors for endometrial cancer. We examined measures of physical activity in relation to endometrial cancer risk in the American Cancer Society Cancer Prevention Study II Nutrition Cohort, a prospective study of cancer incidence and mortality, using information obtained at baseline in 1992. From 1992 to 2003, 466 incident endometrial cancers were identified among 42,672 postmenopausal women with intact uteri who were cancer-free at enrollment. Cox proportional hazards modeling was used to compute hazard rate ratios (RR) while adjusting for potential confounders. To assess the role of body mass index (BMI) in this relationship, we computed multivariate RR with and without adjustment for BMI and stratifying by BMI. All measures of physical activity and the avoidance of sedentary behavior were associated with lower endometrial cancer risk. Baseline recreational physical activity was associated with 33% lower risk (RR = 0.67, 95% CI 0.44-1.03 for 31.5+ vs. <7 MET-hr/week, trend p = 0.007) in the multivariate model without BMI. However, the trend was attenuated after further adjustment for BMI (trend p = 0.18). BMI significantly modified the association between physical activity and endometrial cancer risk (heterogeneity of trends p = 0.01). The inverse relationship was seen only among overweight or obese women (trend p = 0.003) and not in normal weight women (trend p = 0.51). In summary, light and moderate physical activity including daily life activities were associated with lower endometrial cancer risk in our study, especially among women who are overweight or obese.     

Active cigarette smoking and risk of breast cancer

Although epidemiological evidence on the role of active cigarette smoking in breast cancer risk has been inconsistent, recent literature supports a modest association between smoking and breast cancer. This association is particularly observed in women who smoke for a long duration, or who smoke for a long time prior to their first pregnancy. Here, we provide updated results on cigarette smoking and breast cancer risk in the Canadian National Breast Screening Study (NBSS). The NBSS is a large cohort of 89,835 women, aged 40–59, who were followed for a mean of 22.1 years, resulting in the ascertainment of 6,549 incident cases of breast cancer. Cox proportional hazard models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the association of cigarette smoking variables with breast cancer risk. We found breast cancer to be associated with duration (40 years vs. 0: HR = 1.57; 95%CI = 1.29–1.92), intensity (40 cigarettes per day vs. 0: HR = 1.21; 95%CI = 1.04–1.40), cumulative exposure (40 pack‐years vs. 0: HR = 1.19; 95%CI = 1.06–1.13) and latency (40 years since initiation vs. 0: HR = 1.19; 95%CI = 1.10–1.53) of cigarette smoking. Number of years smoked prior to first full‐term pregnancy was associated with higher risk of breast cancer than comparative years smoked post‐pregnancy (among parous women, 5 years pre pregnancy vs. 0: HR = 1.18; 95%CI = 1.10–1.26). These results strongly support a role for cigarette smoking in breast cancer etiology and emphasize the importance of timing of this exposure.     

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.     

A prospective cohort study of cigarette smoking and pancreatic cancer in Japan

Objective: To examine the association of cigarette smoking with the risk of death from pancreatic cancer in a prospective cohort study. Methods: A total of 110,792 inhabitants, aged 40–79 years (46,465 men and 64,327 women), were enrolled from 1988 to 1990 and followed up for mortality to the end of 1997. At baseline a self-administered questionnaire was used to obtain information on cigarette smoking and other lifestyle factors. Results: During the follow-up period (mean ± SD: 8.1 ± 1.8 years), 225 deaths due to pancreatic cancer were identified. After adjustment for age, body mass index, history of diabetes mellitus, and gallbladder diseases, the relative risks (RRs) for current smokers were 1.6 (95% CI 0.95–2.6) in males, and 1.7 (95% CI: 0.84–3.3) in females. Men who smoked more than 40 cigarettes per day had a substantially higher risk of pancreatic cancer, with a RR of 3.3 (95% CI: 1.4–8.1). A significantly decreasing trend in risk with increasing years after smoking cessation was observed (trend p = 0.04) among male ex-smokers. The RRs were 0.85 (95% CI 0.36–2.0) and 0.85 (0.36–2.0) for those who had quit smoking for 10–19 and 20 years, respectively. Conclusions: Our cohort study confirmed that cigarette smoking was associated with an increased risk of death from pancreatic cancer.     

Adherence to the Mediterranean diet and risk of bladder cancer in the EPIC cohort study

There is growing evidence of the protective role of the Mediterranean diet (MD) on cancer. However, to date no epidemiological study has investigated the influence of the MD on bladder cancer. We evaluated the association between adherence to the MD and risk of urothelial cell bladder cancer (UCC), according to tumor aggressiveness, in the European Prospective Investigation into Cancer and Nutrition (EPIC). The analysis included 477,312 participants, recruited from ten European countries between 1991 and 2000. Information from validated dietary questionnaires was used to develop a relative Mediterranean diet score (rMED), including nine dietary components. Cox regression models were used to assess the effect of the rMED on UCC risk, while adjusting for dietary energy and tobacco smoking of any kind. Stratified analyses were performed by sex, BMI, smoking status, European region and age at diagnosis. During an average follow‐up of 11 years, 1,425 participants (70.9% male) were diagnosed with a first primary UCC. There was a negative but non‐significant association between a high versus low rMED score and risk of UCC overall (HR: 0.84 [95% CI 0.69, 1.03]) and risk of aggressive (HR: 0.88 [95% CI 0.61, 1.28]) and non‐aggressive tumors (HR: 0.78 [95% CI 0.54, 1.14]). Although there was no effect modification in the stratified analyses, there was a significant 34% (p = 0.043) decreased risk of UCC in current smokers with a high rMED score. In EPIC, the MD was not significantly associated with risk of UCC, although we cannot exclude that a MD may reduce risk in current smokers.     

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.     

Risk factors for cancers of unknown primary site: Results from the prospective EPIC cohort

Cancer of unknown primary site (CUP) may be called an “orphan” disease, as it is diagnosed when metastases are detected while the primary tumor typically remains undetected, and because little research has been done on its primary causes. So far, few epidemiological studies, if any, have addressed possible risk factors for CUP. We analyzed data from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort (N = 476,940). During prospective follow‐up, a total of 651 cases of incident cases of CUP were detected (ICD‐O‐2 code C809). Proportional hazards models were conducted to examine the associations of lifetime history of smoking habits, alcohol consumption, levels of education and anthropometric indices of adiposity with risk of being diagnosed with CUP. Risk of being diagnosed with CUP was strongly related to smoking, with a relative risk of 3.66 [95% C.I., 2.24–5.97] for current, heavy smokers (26+ cigarettes/day) compared to never smokers (adjusted for alcohol consumption, body mass index, waist circumference and level of education) and a relative risk of 5.12 [3.09–8.47] for cases with CUP who died within 12 months. For alcohol consumption and level of education, weaker associations were observed but attenuated and no longer statistically significant after adjusting for smoking and indices of obesity. Finally, risk of CUP was increased by approximately 30 per cent for subjects in the highest versus lowest quartiles of waist circumference. Our analyses provide further documentation, in addition to autopsy studies, that a substantial proportion of cancers of unknown primary site may have their origin in smoking‐related tumors, in particular.     

Prospective cohort study of cigarette smoking and colorectal cancer risk in women

Epidemiological studies have consistently found a positive association between cigarette smoking and risk of colorectal adenomas, so the absence of a clear association between smoking and colorectal cancer risk may seem paradoxical. However, if colorectal cancer develops only after an induction period of about 35 years, as has been proposed recently, then studies in which all subjects have fewer than about 35 years between smoking commencement and assessment of outcome would be unlikely to detect this association. Few studies have examined smoking of several decades' duration among women. Therefore, in the cohort study reported here, we used proportional hazards models to estimate hazard ratios relating cigarette smoking to colorectal cancer risk among 89,835 women aged 40-59 years at recruitment into the Canadian National Breast Screening Study, a randomized controlled trial of mammography screening for breast cancer. During an average 10.6 years of follow-up (936,433 person-years), a total of 527 women were diagnosed with incident colorectal cancer (363 colon and 164 rectal). We found that smoking was associated with increased risk of rectal cancer 30 years or more after commencement, and especially with smoking of 40 years' duration or longer (hazard ratio=3.14, 95% CI=1.33-7.42). There was little evidence for altered risk of colon cancer. These results, along with those of other recent studies, support the hypothesis that tobacco smoking is an initiator, rather than a promoter, of rectal cancer. However, the results do not support an association with colon cancer risk, even with smoking of very long duration and high intensity.     

Alcohol consumption and prostate cancer risk: results from the Melbourne collaborative cohort study

Although there is little evidence to support an association between alcohol consumption and prostate cancer risk, questions remain concerning the effect on aggressive and nonaggressive tumours and the pattern and type of alcohol consumed. In a prospective cohort of 16,872 men aged 27-70 years at recruitment and followed-up from 1994 to the end of 2003, 732 incident prostate cancers were identified through the local population cancer registry, including 132 aggressive cases and 53 prostate cancer deaths. Detailed information on alcohol consumption was taken at baseline by trained interviewers using a structured questionnaire. Overall, alcohol intake was not associated with prostate cancer incidence. Compared to abstainers, men consuming 1-19 g/d of alcohol had a slightly reduced incidence of aggressive prostate cancers (hazard ratio 0.67; 95% confidence interval (CI) 0.43, 1.06) and prostate cancer mortality (hazard ratio 0.56; 95% CI 0.28, 1.14), but their risk of nonaggressive prostate cancers was close to unity (hazard ratio 1.09; 95% CI 0.85, 1.40). No significant association with pattern of drinking or type of alcoholic beverage was found. Our results show that alcohol consumption does not influence overall prostate cancer incidence but we found suggestive evidence that alcohol consumption might decrease the incidence of aggressive prostate cancer and mortality.     

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.     

Hormonal risk factors for endometrial cancer: modification by cigarette smoking (United States)

Objectives: To evaluate whether smoking modifies the risk of endometrial cancer associated with body mass index (BMI), postmenopausal hormone use, and other hormonal factors. Methods: Using multivariate adjusted models we examined interview data from a population-based case–control study of Wisconsin women (n = 740 cases, n = 2372 controls). Results: The relative risk for endometrial cancer associated with current smoking was 0.8 (95% CI: 0.6–1.0) compared to never smokers. No clear dose–response relationship was evident for pack-years smoked. When examined according to smoking status the risk associated with the highest quartile of BMI seemed to be greater among non-smokers (OR = 3.6, 95% CI: 2.4–5.3) than among current smokers (OR = 2.8, 95% CI: 1.4–5.6). Among postmenopausal women the risk associated with current use of postmenopausal hormones appeared to be greater among non-smokers (OR = 3.3, 95% CI: 2.3–4.9) than among current smokers (OR = 2.7, 95% CI: 1.3–5.5). Risk for long-term use (10 or more years) compared with never users was 8.3 (95% CI: 4.6–15.1) among never smokers and 2.5 (95% CI: 0.8–7.9) among current smokers. The risk associated with non-insulin-dependent diabetes was greater among non-smokers (OR = 2.5, 95% CI: 1.7–3.6) than current smokers (OR = 1.1, 95% CI: 0.4–3.1). There was no modifying effect of smoking on the risk associated with parity. Conclusion: These results suggest that smoking moderates the risk associated with endometrial cancer among women at greatest risk, specifically women who are obese or who use postmenopausal hormones.     

Associations of cigarette smoking and alcohol drinking with stomach cancer survival: A prospective patient cohort study in Japan

Cigarette smoking and alcohol drinking may affect the prognosis of stomach cancer, but evidence has been inconsistent. We investigated the associations between pretreatment smoking and alcohol drinking and the risk of all‐cause and stomach cancer death among 1,576 patients with histologically confirmed stomach cancer diagnosed during 1997–2010 at a single hospital in Japan. Histories of smoking and alcohol drinking were assessed using a self‐administered questionnaire. The patients were followed until December 31, 2013. The Cox proportional hazards model was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). During 9,625.1 person‐years, 670 all‐cause and 419 stomach cancer deaths were documented. Among the patients overall, ever‐drinking was significantly associated with an increased risk of all‐cause death (HR: 1.25; 95% CI: 1.03–1.51), but not stomach cancer death. Positive linear associations with the frequency of drinking (p_trend = 0.02) and the amount of alcohol consumed per day (p_trend = 0.03) were observed for the risk of all‐cause death. Ever‐smoking was not related to either the risk of all‐cause or stomach cancer death. Conversely, among the patients who underwent curative resection, a significant positive association was found between ever‐smoking and the risk of stomach cancer death (HR: 2.44; 95% CI: 1.17–5.08). A positive association was also found for earlier age at start of smoking (p_trend = 0.0046). Pretreatment smoking and alcohol drinking have significant effects on stomach cancer survival. Lifestyle adjustments throughout life may improve survival.     

Serum C-peptide levels and breast cancer risk: results from the European Prospective Investigation into Cancer and Nutrition (EPIC)

It has been hypothesized that chronic hyperinsulinemia, a major metabolic consequence of physical inactivity and excess weight, might increase breast cancer risk by direct effects on breast tissue or indirectly by increasing bioavailable levels of testosterone and estradiol. Within the European Prospective Investigation into Cancer and Nutrition (EPIC), we measured serum levels of C-peptide--a marker for pancreatic insulin secretion--in a total of 1,141 incident cases of breast cancer and 2,204 matched control subjects. Additional measurements were made of serum sex hormone binding globulin (SHBG) and sex steroids. Conditional logistic regression models were used to estimate breast cancer risk for different levels of C-peptide. C-peptide was inversely correlated with SHBG and hence directly correlated with free testosterone among both pre and postmenopausal women. C-peptide and free estradiol also correlated positively, but only among postmenopausal women. Elevated serum C-peptide levels were associated with a nonsignificant reduced risk of breast cancer diagnosed up to the age of 50 years [odds ratio (OR)=0.70, (95% confidence interval (CI), 0.39-1.24); ptrend=0.05]. By contrast, higher levels of C-peptide were associated with an increase of breast cancer risk among women above 60 years of age, however only among those women who had provided a blood sample under nonfasting conditions [OR=2.03, (95% CI, 1.20-3.43); ptrend=0.01]. Our results do not support the hypothesis that chronic hyperinsulinemia generally increases breast cancer risk, independently of age. Nevertheless, among older, postmenopausal women, hyperinsulinemia might contribute to increasing breast cancer risk.     

Alcohol consumption and postmenopausal endometrial cancer: results from the Iowa Women's Health Study

At least three case-control studies have examined the association between alcohol consumption and endometrial cancer; two studies showed inverse associations, and a third a positive association. To our knowledge, no prospective studies of this association have been reported. The association between alcohol and endometrial cancer was examined in the Iowa Women's Health Study (United States), a prospective study of postmenopausal women. Information on alcohol consumption and other variables was obtained through a mailed questionnaire in January 1986. Through December 1990, 167 incident endometrial cancer cases occurred in the at-risk cohort of 25,170 women. Multivariate-adjusted relative risks (RR) and 95 percent confidence intervals (CI) were computed using Cox proportional hazards regression controlling for age, body mass index (BMI), parity, age at menopause, and noncontraceptive estrogen use, and to determine multiplicative interactions. The RRs of endometrial cancer associated with <4.0 and 4.0 g of alcohol per day compared with abstainers were 0.7 (CI=0.5–1.1) and 1.0 (CI=0.7–1.6), respectively. No statistically significant association between endometrial cancer and consumption of either beer, wine, or liquor was observed. There was no interaction between alcohol and any other endometrial cancer risk factors, including BMI or noncontraceptive estrogen use. These data do not support an association between alcohol and endometrial cancer among postmenopausal women.This project was supported by grant RO1-CA39742 to Dr Folsom from the US National Cancer Institute; the contents are solely the responsibility of the authors and do not necessarily represent the official views of the National Cancer Institute. Dr Gapstur was supported by NIH training grant T32-CA09607 to Dr Potter.     

Alcohol and endometrial cancer risk in the NIH‐AARP diet and health study

Previous investigations have provided conflicting results regarding whether alcohol consumption affects endometrial cancer risk, although in many of these studies the highest category of alcohol intake examined was limited. Further, most were unable to resolve how alcohol associations are affected by beverage type, the presence of other endometrial cancer risk factors, or tumor characteristics. To address these issues, we prospectively evaluated the association between alcohol intake and incident endometrial cancer (n = 1,491) in a cohort of 114,414 US women enrolled in the NIH‐AARP Diet and Health Study. We calculated relative risks (RR) and 95% confidence intervals (CI) using Cox proportional hazards regression. After adjustment for age, body mass index (BMI), smoking and other potential confounders, the multivariable RRs (and 95% CIs) compared with nondrinkers were 0.97 (0.87–1.09) for >0–<12 g of alcohol/day, 1.06 (0.87–1.31) for 12–<24 g/day and 0.93 (0.71–1.20) for ≥24 g/day (p trend = 0.90). There was, however, some suggestion of higher risks associated with alcohol consumption among lean women (BMI, <25) and users of menopausal hormone therapy, with significant interactions with both parameters (respective interaction p‐values of 0.002 and 0.005). The relationship was also enhanced, albeit nonsignificantly so, for low grade cancers. Our results do not support that alcohol is a strong contributor to endometrial cancer risk, but slight risk increases may prevail among some users or for selected tumor characteristics.     

Carbohydrate intake, glycemic index and glycemic load in relation to risk of endometrial cancer: A prospective study of Swedish women

The associations of carbohydrate intake, glycemic index and glycemic load with endometrial cancer risk were examined among 61,226 participants of the Swedish Mammography Cohort who were cancer-free at enrollment between 1987 and 1990 and completed a food frequency questionnaire. During a mean follow-up of 15.6 years, through June 2005, 608 incident cases of endometrial adenocarcinoma were diagnosed. We observed no overall association between carbohydrate intake, glycemic index or glycemic load and incidence of endometrial cancer; the rate ratios (RRs) for the highest versus the lowest quintile were 1.12 (95% CI, 0.85-1.47) for carbohydrate intake, 1.00 (95% CI, 0.77-1.30) for glycemic index and 1.15 (95% CI, 0.88-1.51) for glycemic load. However, among obese women (body mass index, BMI > or =30 kg/m2), endometrial cancer incidence was nonsignificantly elevated in the top versus bottom quintiles of carbohydrate intake (RR, 1.68; 95% CI, 0.86-3.29) and glycemic load (RR, 1.57; 95% CI, 0.82-2.99). In a subanalysis of women who completed a follow-up questionnaire in 1997, which collected information on physical activity, carbohydrate intake and glycemic load were positively related to endometrial cancer risk among overweight women (BMI > or =25 kg/m2) with low physical activity. In this subgroup, the multivariate RRs comparing extreme quartiles were 1.90 (95% CI, 0.84-4.31) for carbohydrate intake and 2.99 (95% CI, 1.17-7.67) for glycemic load. Results from this cohort study suggest that a high carbohydrate intake and a high glycemic load may increase the risk of endometrial cancer among overweight women with low physical activity.     

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.     

Breast cancer risk in relation to abortion: Results from the EPIC study

The role of spontaneous and induced abortion on breast cancer risk is examined among 267,361 women recruited into the European Prospective Investigation into Cancer and nutrition between 1992 and 2000. The data were collected from 20 centers, across 9 countries, and included information on a total of 4,805 women with breast cancer, of whom 1,657 reported having ever had any type of abortion. Overall, the relative risk of breast cancer in women who reported ever having had a spontaneous abortion was not significantly elevated when compared with women who reported never having had such an abortion (RR = 1.07, 95% CI = 0.99-1.14). However, there was some evidence of a slight increase in the risk of breast cancer among women who reported having had 2 or more spontaneous abortions (1.20, 1.07-1.35). The relative risk of breast cancer among women who reported ever having had an induced abortion when compared to women who reported never having had an induced abortion was 0.95 (0.87-1.03). Overall, the findings provide further unbiased evidence of the lack of an adverse effect of induced abortion on breast cancer risk.