Objective: High-glycaemic-load diets may increase endometrial cancer risk by increasing circulating insulin levels and, as a consequence, circulating oestrogen levels. Given the paucity of epidemiological data regarding the relationship between dietary glycaemic index and glycaemic load and endometrial cancer risk, we sought to examine these associations using data from a prospective cohort study.Design, setting and subjects: We examined the association between dietary glycaemic load and endometrial cancer risk in a cohort of 49 613 Canadian women aged between 40 and 59 years at baseline who completed self-administered food-frequency questionnaires between 1982 and 1985. Linkages to national mortality and cancer databases yielded data on deaths and cancer incidence, with follow-up ending between 1998 and 2000.Results: During a mean of 16.4 years of follow-up, we observed 426 incident cases of endometrial cancer. Hazard ratios for the highest versus the lowest quartile level of overall glycaemic index and glycaemic load were 1.47 (95% confidence interval (CI)=0.90-2.41; P for trend=0.14) and 1.36 (95% CI=1.01-1.84; P for trend=0.21), respectively. No association was observed between total carbohydrate or total sugar consumption and endometrial cancer risk. Among obese women (body mass index > 30 kg m(-2)) the hazard ratio for the highest versus the lowest quartile level of glycaemic load was 1.88 (95% CI=1.08-3.29; P for trend=0.54) and there was a 55% increased risk for the highest versus the lowest quartile level of glycaemic load among premenopausal women. There was also evidence to support a positive association between glycaemic load and endometrial cancer risk among postmenopausal women who had used hormone replacement therapy.Conclusions: Our data suggest that diets with high glycaemic index or high glycaemic load may be associated with endometrial cancer risk overall, and particularly among obese women, premenopausal women and postmenopausal women who use hormone replacement therapy.

We thank Dr. Hocking for his useful comments concerning our study on occupational risk factors and high grade and low grade glioma. We agree that there are some methodological limitations in this study, which was carried out in the late 80s. For example, assessment of exposure to different types of electromagnetic fields could not be investigated at that time in the same way that would be possible today. We also agree that misclassification is a potential problem. It might indeed be difficult for people suffering from severe brain tumours to answer detailed questions on specific exposures associated with employment. Although all study centres used well-trained interviewers, the possibility cannot be excluded that recall bias due to lack of memory may have influenced the information on past exposure to occupational agents. This potential problem is an issue for most other brain tumour studies. In our present study, efforts were made to schedule interviews as soon as possible after diagnosis. For cases who were too ill to answer questions, or who had already died, we interviewed proxy subjects in order to minimize bias that would have occurred if very severe cases had been excluded. Although we are aware of the problematic nature of information given by proxies, we decided to include their information in the analyses because sensitivity tests, including and excluding the proxy interviews, did not change the estimation of the risks substantially. Because people may not be aware of all the substances to which they are exposed at work, our main emphasis concerning interpretation of the results is focussed more on occupational activities than on substance exposure. Because of these problems, we are very careful in the interpretation of our results, especially when odds ratios did not reach statistical significance or when results were not consistent between the study centers. Numerous other epidemiological studies have investigated the role of occupational exposures in the development of brain tumours with inconsistent findings. Despite the limitations mentioned above, our results are based on one of the largest case-control-studies on incident brain tumours in adults, and the data do not suggest that occupational exposure is a major risk factor for glioma development. Yours sincerely, Brigitte Schlehofer, Iris Hettinger, Maria Blettner, Susan Preston-Martin, Annie Arslan, Anders Ahlbom, Won N. Choi, Graham G. Giles, Geoffrey R. Howe, Julian Little, Francoise Ménégoz, Ylva Rodvall, Philip Ryan, Jürgen Wahrendorf..

The majority of suspected occupational risk factors for adult brain tumours have yet to be confirmed as etiologically relevant. Within an international case‐control study on brain tumours, lifelong occupational histories and information on exposures to specific substances were obtained by direct interviews to further investigate occupational risk factors for glioma. This is one of the largest studies of brain tumours in adults, including 1,178 cases and 1987 population controls from 8 collaborating study centres matched for age, gender and centre. All occupational information, was aggregated into 16 occupational categories. In a pooled analysis, odds ratios (OR), adjusted for education, were estimated separately for men and women and for high‐grade glioma (HGG) and low‐grade glioma (LGG), focusing especially on 6 categories defined a priori: agricultural, chemical, construction, metal, electrical/electronic and transport. For men, an elevated OR of glioma associated with the category “metal” (OR = 1.24, 95% CI 0.96–1.62) was seen, which appeared to be largely accounted for by LGG (OR = 1.59, 95% CI 1.00–2.52). For the other 5 occupational categories, no elevated risks for glioma were observed. For women the only noteworthy observation for the 6 a priori categories was an inverse association with the “agriculture” category (OR = 0.60, 95% CI 0.36–0.99). Apart from the 6 major categories, women working in food production or food processing (category “food”) showed an increased OR of 1.95 (95% CI 1.04–3.68). None of the 20 substance groups was positively associated with glioma risk. Although some other point estimates were elevated, they lacked statistical significance. The results do not provide evidence of a strong association between occupational exposures and glioma development.

BACKGROUND:Many studies of fruit and vegetable consumption showed inverse associations with breast cancer risk, suggesting the potential importance of carotenoids (and other phytochemicals) contained in these foods. To date, however, only one prospective cohort study has examined dietary carotenoids other than beta-carotene in relation to breast cancer risk.OBJECTIVE:Our aim was to examine the relations between dietary intakes of beta-carotene, alpha-carotene, beta-cryptoxanthin, lycopene, and lutein + zeaxanthin and breast cancer risk in a large cohort study of Canadian women.DESIGN:A case-cohort analysis was undertaken in a cohort of 56 837 women who were enrolled in the Canadian National Breast Screening Study and who completed a self-administered dietary questionnaire. During follow-up to the end of 1993 a total of 1589 women were diagnosed with biopsy-confirmed incident breast cancer. For comparison, a subcohort of 5681 women was randomly selected. After exclusions for various reasons, the analyses were based on 1452 cases and 5239 noncases.RESULTS:We found no clear association between intakes of any of the studied carotenoids and breast cancer risk in the study population as a whole or in subgroups defined by smoking status; relative body weight (assessed by body mass index); intakes of total fat, energy, alcohol, or folic acid; family history of breast cancer; or menopausal status.CONCLUSIONS:Our data do not support any association between dietary intakes of the studied carotenoids and breast cancer risk. However, prospective cohort studies of carotenoids in relation to breast cancer are scarce and further studies are warranted.

While numerous studies have addressed the possible role of farming and related exposures as risk factors for brain tumours in adults, few of them have examined the potential effect of exposure to farm animals or pets. In an international multicentre case–control study, we investigated whether residence on a farm, contact with animals, or working in occupations with a high degree of potential contact with animals or humans were associated with brain tumours. Using a common questionnaire, 1177 cases of glioma, 330 with meningioma and 2478 controls from eight centres were interviewed about the exposures and, in particular, about their contacts with nine species of animals: dairy cattle, beef cattle, pigs, horses, sheep, goats, poultry, dogs and cats. Living or working on a farm was not a risk factor, for either glioma or meningioma. Except in some centres, there was no relationship between having contacts with farm animals or pets and the risk of brain tumour, for either type of tumour or either sex. In relation to seven industrial groups involving frequent human and/or animal contacts, no association was apparent for either glioma or meningioma. In relation to 25 occupational groups with potential frequent contact with humans and/or animals, for glioma there was a reduced risk for biological technicians (Odds Ratio (OR)/=0, P=0.01), and general farm workers (OR=0.66, 95% Confidence Interval (CI): 0.5–0.9). For meningioma, there was an increased risk for cooks (OR=2.0; CI: 1.2–3.4). With some exceptions, these results indicate no association between either the type of brain tumour and contacts with animals, or with occupations that include a high level of contact with animals or a high level of contact with humans.

Folate is crucial for normal DNA methylation, synthesis and repair, and deficiency of this nutrient is hypothesized to lead to cancer through disruption of these processes. There is some evidence to suggest that relatively high dietary folate intake might be associated with reduced colorectal cancer risk, especially among individuals with low methionine intake. A case-cohort analysis was undertaken within the cohort of 56,837 women who were enrolled in the Canadian National Breast Screening Study and who completed a self-administered dietary questionnaire. During follow-up to the end of 1993, a total of 389 women were diagnosed with colorectal cancer, identified by linkage to the Canadian Cancer Database. For comparative purposes, a subcohort of 5,681 women was randomly selected from the full dietary cohort at baseline. After exclusions for various reasons, the analyses were based on 295 cases and 5,334 non-cases. Folate intake was inversely associated with colorectal cancer risk (IRR = 0.6, 95% CI = 0.4-1.1, p for trend = 0.25). The inverse association was essentially similar among individuals with low and high methionine intake, and was similar for colon and rectal cancers when those endpoints were analyzed separately. Among individuals with low methionine intake, folate intake did not appear to lower the risk of rectal cancer, a finding that may be due, in part, to the low number of cases in the subgroup analysis. Overall, our data lend some support to the hypothesis that high folate intake is associated with a reduced risk of colorectal cancer.

The evidence for a protective effect of vegetables, fruits, and legumes against prostate cancer is weak and inconsistent. We examined the relationship of these food groups and their constituent foods to prostate cancer risk in a multicenter case-control study of African-American, white, Japanese, and Chinese men. Cases (n = 1619) with histologically confirmed prostate cancer were identified through the population-based tumor registries of Hawaii, San Francisco, and Los Angeles in the United States and British Columbia and Ontario in Canada. Controls (n = 1618) were frequency-matched to cases on ethnicity, age, and region of residence of the case, in a ratio of approximately 1:1. Dietary and other information was collected by in-person home interview; a blood sample was obtained from control subjects for prostate-specific antigen determination. Odds ratios (OR) were estimated using logistic regression, adjusting for age, geographic location, education, calories, and when indicated, ethnicity. Intake of legumes (whether total legumes, soyfoods specifically, or other legumes) was inversely related to prostate cancer (OR for highest relative to lowest quintile for total legumes = 0.62; P for trend = 0.0002); results were similar when restricted to prostate-specific antigen-normal controls or to advanced cases. Intakes of yellow-orange and cruciferous vegetables were also inversely related to prostate cancer, especially for advanced cases, among whom the highest quintile OR for yellow-orange vegetables = 0.67 (P for trend = 0.01) and the highest quintile OR for cruciferous vegetables = 0.61 (P for trend = 0.006). Intake of tomatoes and of fruits was not related to risk. Findings were generally consistent across ethnic groups. These results suggest that legumes (not limited to soy products) and certain categories of vegetables may protect against prostate cancer.

We investigated the relation between benign ovarian tumours and lactose among 746 case women identified at seven New York metropolitan hospitals and 404 community controls, age and hospital frequency matched to the expected case distribution. No increase in risk was found for lactose (highest quartile versus lowest: adjusted odds ratio = 0.82 (95% CI 0.57–1.20) or for any other lactose foods. © 2000 Cancer Research Campaign http://www.bjcancer.com

Estrogen therapy reduces the risk of osteoporosis and cardiovascular diseases but is associated with an increased risk of endometrial cancer. We have assessed the impact of a regimen of estrogen with progestogen on risk of endometrial cancer for women 48 years and older. We conducted a case-control study in Ontario, Canada, from 1994 to 1998 by interviewing registry-based cases (n = 512) and population controls (n = 513) to obtain information on use of hormones and dietary habits. Compared to non-users, the use of opposed hormone therapy in sequential regimen for more than three years showed a borderline increase in risk (OR = 1.49, 95% CI 0.93–2.40), but this increase was much less than among women on unopposed estrogen (OR = 4.12, 95% CI 2.21–7.71). Stronger associations were observed when duration of sequential hormone use was examined as a continuous variable (OR per three years of use = 1.21, 95% CI 1.03–1.42). The effect of opposed hormone therapy on endometrial cancer risk appears to vary both by usage patterns and by patient characteristics of body weight and history of diabetes.

There have been relatively few epidemiological studies to verify the information obtained from study participants on the use of menopausal hormone replacement therapy. We conducted this study as part of a case-control study of diet, hormone use, and endometrial cancer in Toronto, Ontario, Canada, 1994-1998. We compared records from 653 subjects, 30-79 years of age, with reports from their physicians on ever/never use of hormone replacement therapy and duration, type, and dose of hormone replacement therapy. A total of 88% of the interview records were in agreement with physician reports for ever/never use of hormone replacement therapy. The overall kappa value for ever/never use agreement was 0.76 (range = 0.71-0.81), and the intraclass correlation coefficient was 0.64 (range = 0.57-0.70) for duration of hormone replacement therapy use, indicating good agreement; similar correlations were seen among cases and controls for overall use, as well as estrogen- or progestogen-alone use. Concordance for brand codes was observed for about 43% of the subjects. This study suggests that information obtained by interview in case-control studies provides a reasonable measure of ever use of hormone replacement therapy and duration of use. Interviews, however, do not represent a reliable source of information on brands and dosage of hormone replacement therapy preparations.

In an international population-based case-control study carried out in 8 centres in 6 countries, we investigated the role of specific medical conditions in the aetiology of brain tumours in adults. Recruited were 1,178 glioma and 331 meningioma cases and 2,493 age- and gender-matched population controls. Only medical conditions occurring at least 2 years before brain tumour diagnosis were considered. Relative risks (RRs) and 95% confidence intervals (CIs) were estimated using a conditional logistic regression model. Heterogeneity between centres was tested. No association between meningioma and previous medical conditions was observed. For glioma, there was an increased risk associated with epilepsy (RR = 6.55, 95% CI 3.40-12.63), but this was considerably weaker for epilepsy of more than 20 years duration. The risk remained elevated after adjustment for use of anti-epileptic drugs. There was a statistically significant inverse association between glioma and all allergic diseases combined (RR = 0.59, 95% CI 0.49-0.71); this was also observed for specific allergic conditions, namely, asthma and eczema. Subjects who reported a history of infectious diseases (e.g., colds, flu) showed a 30% reduction in risk (RR = 0.72, 95% CI 0.61-0.85). The decreased risks for glioma in subjects reporting a history of allergic conditions or infectious diseases may indicate an influence of immunological factors on the development of glioma. The association between glioma and epilepsy has to be interpreted cautiously and needs further investigation.

Epidemiological data on most cancer sites suggest that consumption of plant foods, which contain high levels of antioxidants, might slow or prevent the appearance of cancer. We used data from three case-control studies to test this hypothesis. The total study population consisted of 617 incident cases of prostate cancer and 636 population controls from Ontario, Quebec, and British Columbia. Dietary information was collected by an in-person interview with a detailed quantitative dietary history. Unconditional logistic regression analyses were performed to estimate odds ratios (ORs) and 95% confidence intervals (CIs). A decreasing, statistically significant association was found with increasing intakes of green vegetables (OR = 0.54, 95% CI = 0.40-0.71 for 4th quartile), tomatoes (OR = 0.64, 95% CI = 0.45-0.91), beans/lentils/nuts (OR = 0.69, 95% CI = 0.53-0.91), and cruciferous vegetables (OR = 0.69, 95% CI = 0.52-0.91 for 3rd quartile). Higher intakes of fruit were associated with higher ORs (OR = 1.51, 95% CI = 1.14-2.01 for 4th quartile), an effect that was seen for total fruit and citrus fruit, as well as for all other noncitrus fruits. Among the grains, refined-grain bread intake was associated with a decrease in risk (OR = 0.65 for 4th quartile), whereas whole-grain breakfast cereals were associated with a higher risk for prostate cancer. Of all the antioxidant nutrients studied, the ORs were higher with higher intakes of cryptoxanthin (OR = 1.44, 95% CI = 1.09-1.89 for 4th quartile). Exposure to certain dietary components of plant origin, which are potentially modifiable, indicates the theoretical scope for reducing the risk from prostate cancer. Future experimental studies or trials are warranted for further understanding.

To assess the risk of invasive breast cancer associated with total and beverage-specific alcohol consumption and to evaluate whether dietary and nondietary factors modify the association.We included in these analyses 6 prospective studies that had at least 200 incident breast cancer cases, assessed long-term intake of food and nutrients, and used a validated diet assessment instrument. The studies were conducted in Canada, the Netherlands, Sweden, and the United States. Alcohol intake was estimated by food frequency questionnaires in each study. The studies included a total of 322647 women evaluated for up to 11 years, including 4335 participants with a diagnosis of incident invasive breast cancer.Pooled analysis of primary data using analyses consistent with each study's original design and the random-effects model for the overall pooled analyses.For alcohol intakes less than 60 g/d (reported by >99% of participants), risk increased linearly with increasing intake; the pooled multivariate relative risk for an increment of 10 g/d of alcohol (about 0.75-1 drink) was 1.09 (95% confidence interval [CI], 1.04-1.13; P for heterogeneity among studies, .71). The multivariate-adjusted relative risk for total alcohol intakes of 30 to less than 60 g/d (about 2-5 drinks) vs nondrinkers was 1.41 (95% CI, 1.18-1.69). Limited data suggested that alcohol intakes of at least 60 g/d were not associated with further increased risk. The specific type of alcoholic beverage did not strongly influence risk estimates. The association between alcohol intake and breast cancer was not modified by other factors.Alcohol consumption is associated with a linear increase in breast cancer incidence in women over the range of consumption reported by most women. Among women who consume alcohol regularly, reducing alcohol consumption is a potential means to reduce breast cancer risk.

Background Increased brain tumour risk after head trauma suggested by case reports and clinical series has been previously studied epidemiologically with mixed results. An international multicentre case-control study investigated the role of head trauma from injury or sports participation in adult brain tumour risk.Methods In all, 1178 glioma and 330 meningioma cases were individually or frequency matched to 2236 controls. Only exposures that occurred at least 5 years before diagnosis and head injuries that received medical attention were considered.Results Risk for ever having experienced a head injury was highest for male meningiomas (odds ratio [OR] = 1.5, 95% confidence interval [CI] : 0.9-2.6) but was lower for 'serious' injuries, i.e. those causing loss of consciousness, loss of memory or hospitalization (OR = 1.2, 95% CI: 0.6-2.3). Among male meningiomas, latency of 15 to 24 years significantly increased risk (OR = 5.4, 95% CI: 1.7-16.6), and risk was elevated among those who participated in sports most correlated with head injury (OR = 1.9, 95% CI : 0.7-5.3). Odds ratios were lower for male gliomas (OR = 1.2, 95% CI : 0.9-1.5 for any injury; OR = 1.1, 95% CI : 0.7-1.6 for serious injuries) and in females in general.Conclusions Evidence for elevated brain tumour risk after head trauma was strongest for meningiomas in men. Findings related to sports should be interpreted cautiously due to cultural variability in our data and our lack of complete data on physical exercise in general which appeared to be protective.

OBJECTIVETo assess the risk of invasive breast cancer associated with total and beverage-specific alcohol consumption and to evaluate whether dietary and nondietary factors modify the association.DATA SOURCESWe included in these analyses 6 prospective studies that had at least 200 incident breast cancer cases, assessed long-term intake of food and nutrients, and used a validated diet assessment instrument. The studies were conducted in Canada, the Netherlands, Sweden, and the United States. Alcohol intake was estimated by food frequency questionnaires in each study. The studies included a total of 322647 women evaluated for up to 11 years, including 4335 participants with a diagnosis of incident invasive breast cancer.DATA EXTRACTIONPooled analysis of primary data using analyses consistent with each study's original design and the random-effects model for the overall pooled analyses.DATA SYNTHESISFor alcohol intakes less than 60 g/d (reported by >99% of participants), risk increased linearly with increasing intake; the pooled multivariate relative risk for an increment of 10 g/d of alcohol (about 0.75-1 drink) was 1.09 (95% confidence interval [CI], 1.04-1.13; P for heterogeneity among studies, .71). The multivariate-adjusted relative risk for total alcohol intakes of 30 to less than 60 g/d (about 2-5 drinks) vs nondrinkers was 1.41 (95% CI, 1.18-1.69). Limited data suggested that alcohol intakes of at least 60 g/d were not associated with further increased risk. The specific type of alcoholic beverage did not strongly influence risk estimates. The association between alcohol intake and breast cancer was not modified by other factors.CONCLUSIONSAlcohol consumption is associated with a linear increase in breast cancer incidence in women over the range of consumption reported by most women. Among women who consume alcohol regularly, reducing alcohol consumption is a potential means to reduce breast cancer risk.

There are very few large scale studies that have examined the association of prostate cancer with alcohol and other beverages. This relationship was examined in a case-control study conducted in 3 geographical areas of Canada [Metropolitan Toronto (Ontario), Montreal (Quebec), and Vancouver (British Columbia)] with 617 incident cases and 637 population controls. Complete history of beverage intake was assessed by a personal interview with reference to a I-year period prior to diagnosis or interview. In age- and energy-adjusted models for all centers combined, the odds ratio (OR) for the highest quintile of total alcohol intake was 0.89. For alcoholic beverages separately, it was 0.68 for the highest tertile of beer, 1.12 for wine and 0.86 for liquor. The decreasing trend war significant for beer intake. The results were only significant for British Columbia out of all the 3 centers studied. Whereas coffee and cola intake was not associated with prostate cancer, a decrease in risk was observed with tea intake of more than 500 g per day (OR 0.70). Our results do not support a positive association between total alcohol, coffee and prostate cancer. (C) 1998 Wiley-Liss, Inc.

BACKGROUNDThere are few previous epidemiologic studies of gallbladder cancer, a rare but nearly always lethal gastrointestinal cancer with a demonstrated greater frequency in adult women and older subjects of both sexes, and also in the members of populations throughout central and eastern Europe and certain racial groups such as native American Indians. Unfortunately, the prospects for the prevention of this form of cancer are poor.PURPOSEOur purpose in conducting this study was to investigate possible new risk factors for gallbladder cancer and to strengthen our understanding of established causal agents that may be involved in this disease.METHODSA large, collaborative, multicenter, case-control study of cancer of the gallbladder was conducted in five centers located in Australia (Adelaide), Canada (Montreal and Toronto), The Netherlands (Utrecht), and Poland (Opole) from January 1983 through July 1988. Case subjects with gallbladder cancer were accrued by the centers from hospital pathology records and from reports to regional cancer registries. Cancer diagnosis was confirmed by either biopsy, cholecystectomy, or at the time of autopsy. Control subjects were randomly assigned at each center from the population. The pooled analysis included 196 case subjects and 1515 control subjects (who did not report previous cholecystectomy). Ninety-eight percent of the subjects were white. Personal interviews of case subjects, control subjects, and surrogates (spouse or next of kin) were conducted by trained personnel.RESULTSAfter adjusting for potential confounding factors (age, sex, center, type of interview, years of schooling, alcohol intake, and lifetime cigarette smoking), a history of gallbladder symptoms requiring medical attention (e.g., reduced bile secretion from the gallbladder into the small intestine due to obstructions of the common bile or cystic ducts) was the major risk factor associated with this form of cancer (odds ratio [OR] = 4.4; 95% confidence interval [CI] = 2.6-7.5). This association was present even in subjects who had their first gallbladder examination because of symptoms present more than 20 years earlier (OR = 6.2; 95% CI = 2.8-13.4). Other variables associated with gallbladder cancer risk included an elevated body mass index, high total energy intake, high carbohydrate intake (after adjustment for total energy intake), and chronic diarrhea. All of these risk factors have been previously associated with gallstone disease.CONCLUSIONSThese findings are consistent with a major role of gallstones, or risk factors for gallstones, in the cause of gallbladder cancer. Additional information on whether or not screening high-risk subjects for gallstones or gallbladder cancer is needed.

In a population-based case-control study of prostate cancer conducted in Montreal, Toronto and Vancouver between 1989 and 1993, a total of 640 newly incident cases and 639 aged-matched population controls were interviewed as to their family history of prostate cancer as well as nutritional and other lifestyle and environmental factors. In total, 94 cases (15%) reported at least one blood relative with a family history, as compared with 32 (5%) of controls, giving a relative risk of 3.32 (95% confidence interval 2.18-5.05). The association was very consistent across all 3 centers, and was similar for each specific type of relative considered (fathers or brothers). Thus, this study provides further evidence of familial aggregation of prostate cancer, and suggests the possibility that part or all of such clustering could be related to inherited genetic patterns; if so, the availability of screening procedures for the disease offers the possibility of useful early intervention in individuals with such inherited susceptibility.