Meat consumption, N-acetyl transferase 1 and 2 polymorphism and risk of breast cancer in Danish postmenopausal women.

The aim of this study was to investigate whether polymorphisms in N-acetyl transferase 1 and 2 modify the association between meat consumption and risk of breast cancer. A nested case-control study was conducted among 24 697 postmenopausal women included in the 'Diet, Cancer and Health' cohort study (1993-2000). Three hundred and seventy-eight breast cancer cases were identified and matched to 378 controls. The incidence rate ratio (95% confidence interval) for breast cancer was 1.09 (1.02-1.17) for total meat, 1.15 (1.01-1.31) for red meat and 1.23 (1.04-1.45) for processed meat per 25 g daily increment in intake. Compared with slow acetylators, the IRR (95% confidence interval) among fast N-acetyl transferase 1 acetylators was 1.43 (1.03-1.99) and 1.13 (0.83-1.54) among intermediate/fast N-acetyl transferase 2 acetylators. Interaction analyses revealed that the positive associations between total meat intake and red meat intake and breast cancer risk were confined to intermediate/fast N-acetyl transferase 2 acetylators (Pinteraction = 0.03 and 0.04). Our findings support an association between meat consumption and breast cancer risk and that N-acetyl transferase 2 polymorphism has a modifying effect on the association, indicating that the association is confined to only genetically susceptible women.

Study design, exposure variables, and socioeconomic determinants of participation in Diet, Cancer and Health: a population-based prospective cohort study of 57,053 men and women in Denmark.

AIMS: Diet is considered an important aspect of lifestyle related to cancer development. To contribute further knowledge within this field a Danish prospective cohort study "Diet, Cancer and Health" has been initiated. The aims of this paper are to give a description of the study design, measurement procedures, and differences between participants and non-participants with special reference to socioeconomic characteristics. METHODS: A total of 160,725 individuals 50-64 years of age living in Copenhagen or Aarhus were invited to participate. Information concerning diet and other lifestyle factors was obtained from 57,053 participants using questionnaires and interviews. Anthropometric measurements were taken and biological material collected. In addition, detailed (selected) socioeconomic information on all invited persons including 103,671 non-participants was obtained from statistical registers in Statistics Denmark. RESULTS: Differences were seen between participants and non-participants on a number of socioeconomic factors. The highest participation in relation to education was found among participants with higher education, with a significant tendency to be highest in the second highest level of higher education (3-4 years). Married people were more likely to participate than persons living alone or cohabiting. CONCLUSION: Results from the prospective cohort study "Diet, Cancer and Health" support the general assumption that lower socioeconomic groups are underrepresented in epidemiological studies.

Alcohol intake and breast cancer risk: the European Prospective Investigation into Cancer and Nutrition (EPIC).

OBJECTIVE: Most epidemiologic studies have suggested an increased risk of breast cancer with increasing alcohol intake. Using data from 274,688 women participating in the European Prospective Investigation into Cancer and Nutrition study (EPIC), we investigated the relation between alcohol intake and the risk of breast cancer. METHODS: Incidence rate ratios (IRRs) based on Cox proportional hazard models were calculated using reported intake of alcohol, recent (at baseline) and lifetime exposure. We adjusted for known risk factors and stratified according to study center as well as potentially modifying host factors. RESULTS: During 6.4 years of follow up, 4,285 invasive cases of breast cancer within the age group 35-75 years were identified. For all countries together the IRR per 10 g/day higher recent alcohol intake (continuous) was 1.03 (95% confidence interval (CI): 1.01-1.05). When adjusted, no association was seen between lifetime alcohol intake and risk of breast cancer. No difference in risk was shown between users and non-users of HRT, and there was no significant interaction between alcohol intake and BMI, HRT or dietary folate. CONCLUSION: This large European study supports previous findings that recent alcohol intake increases the risk of breast cancer.

Dietary intake of different types and characteristics of processed meat which might be associated with cancer risk--results from the 24-hour diet recalls in the European Prospective Investigation into Cancer and Nutrition (EPIC).

OBJECTIVE: There is increasing evidence for a significant effect of processed meat (PM) intake on cancer risk. However, refined knowledge on how components of this heterogeneous food group are associated with cancer risk is still missing. Here, actual data on the intake of PM subcategories is given; within a food-based approach we considered preservation methods, cooking methods and nutrient content for stratification, in order to address most of the aetiologically relevant hypotheses. DESIGN AND SETTING: Standardised computerised 24-hour diet recall interviews were collected within the framework of the European Prospective Investigation into Cancer and Nutrition (EPIC), a prospective cohort study in 27 centres across 10 European countries. SUBJECTS: Subjects were 22,924 women and 13,031 men aged 35-74 years. RESULTS: Except for the so-called 'health-conscious' cohort in the UK, energy-adjusted total PM intake ranged between 11.1 and 47.9 g day(-1) in women and 18.8 and 88.5 g day(-1) in men. Ham, salami-type sausages and heated sausages contributed most to the overall PM intake. The intake of cured (addition of nitrate/nitrite) PM was highest in the German, Dutch and northern European EPIC centres, with up to 68.8 g day(-1) in men. The same was true for smoked PM (up to 51.8 g day(-1)). However, due to the different manufacturing practice, the highest average intake of NaNO2 through PM consumption was found for the Spanish centres (5.4 mg day(-1) in men) as compared with German and British centres. Spanish centres also showed the highest intake of NaCl-rich types of PM; most cholesterol- and iron-rich PM was consumed in central and northern European centres. Possibly hazardous cooking methods were more often used for PM preparation in central and northern European centres. CONCLUSIONS: We applied a food-based categorisation of PM that addresses aetiologically relevant mechanisms for cancer development and found distinct differences in dietary intake of these categories of PM across European cohorts. This predisposes EPIC to further investigate the role of PM in cancer aetiology.

Fish consumption and breast cancer risk. The European Prospective Investigation into Cancer and Nutrition (EPIC).

There is current interest in fish consumption and marine omega-3 (n-3) fatty acids and breast cancer risk. Some in vitro and animal studies have suggested an inhibitory effect of marine n-3 fatty acids on breast cancer growth, but the results from epidemiological studies that have examined the association between fish consumption and breast cancer risk in humans are inconsistent. We examined fish consumption and breast cancer risk in 310,671 women aged between 25 and 70 yr at recruitment into the European Prospective Investigation Into Cancer and Nutrition (EPIC). The participants completed a dietary questionnaire between 1992-98 and were followed up for incidence of breast cancer for a median of 6.4 yr. Hazard ratio for breast cancer by intake of total and lean and fatty fish were estimated, stratified by study centre and adjusted for established breast cancer risk factors. During follow-up, 4,776 invasive incident breast cancers were reported. No significant associations between intake of total fish and breast cancer risk were observed, hazard ratio (HR) 1.01 (95% confidence interval [CI] 0.99-1.02; p = 0.28 per 10 g fish/day). When examining lean and fatty fish separately, we found a positive significant association only in the highest quintile for fatty fish (HR 1.13, 95% CI 1.01-1.26), but test for trend was not significant (p = 0.10). No associations with breast cancer risk were observed when the study participants were subdivided by menopausal status. Although the period of follow-up is relatively short, the results provide no evidence for an association between fish intake and breast cancer risk.

Does high intake of fruit and vegetables improve lung cancer survival?

The objective of the study was to examine the prognostic effect of dietary intake of fruit and vegetables on lung cancer patients. We used data on 57,053 participants in the Danish prospective cohort study, 'Diet, Cancer and Health'. Patients in whom lung cancer was diagnosed constituted the final study cohort and were followed from the date of diagnosis until the date of death or 11 March 2004. A total of 353 participants had lung cancer. Increasing levels of intake of fruit and vegetables show a tendency toward decreased hazard of dying: the Cox proportional hazard model estimated a hazard ratio (HR) of 0.84 (95% confidence interval [CI], 0.59-1.21) for high intake of vegetables by current smokers and an HR of 0.81 (95% CI, 0.58-1.15) for high intake of fruits with low intake as the reference. In contrast, high intake of potatoes increased the hazard of dying (HR, 1.51; 95% CI, 1.12-2.23). Our study suggests that high intake of fruit and vegetables might have a favourable effect on the prognosis of lung cancer patients, but a high intake of potatoes appears to increase the hazard of dying.

Organochlorines in Danish women: predictors of adipose tissue concentrations.

Organochlorines (OCs) are ubiquitously present in the environment, and food of animal origin is currently reported as the major source of exposure. Carcinogenicity in animals raises concern, and OCs may also be a risk factor for both neurological and immunological effects. Our primary objective was to study predictors of adipose tissue levels of dichlorodiphenyldichloroethylene (DDE) and polychlorinated biphenyls (PCBs) in Danish women. We showed that adipose tissue concentrations of DDE and PCBs were consistently positively associated with age and the consumption of fish with a high fat content, while total lifetime duration of lactation had an inverse relationship. The direction of the association with body mass index (BMI) depended on the OC studied. The consumption of meat, fruit, lean fish, medium-fat-content fish, poultry, and eggs was not associated with OC concentrations in our study. We classified fish according to fat percentage, which seems more relevant than considering only total fish consumption. When PCBs were subdivided according to their chemical structure, similar results were obtained for the mono-, di-, and tri-ortho PCBs, indicating that PCBs can be treated as a homogenous group when studying predictors of concentrations in humans. In conclusion, the present study shows that age, lactation, and BMI are consistent predictors of human adipose tissue concentrations of DDE and PCBs and that dietary factors other than fish with a high fat content are not important predictors of these concentrations.

Diet and risk of rheumatoid arthritis in a prospective cohort.

OBJECTIVE: To assess the association between dietary factors and risk of rheumatoid arthritis (RA) in a large prospective cohort. METHODS: Information about dietary intake was obtained from a detailed self-administered food frequency questionnaire completed by 57,053 individuals who participated in a prospective cohort. Linking the cohort to the Danish National Patient Registry we identified patients who developed RA. A rheumatologist scrutinized original medical records for these individuals in order to confirm the diagnosis of RA. Cox proportional hazards regression analyses were performed for dietary and lifestyle factors. RESULTS: The average time of followup in the cohort was 5.3 years (range < 1 mo to 7.7 yrs). Sixty-nine individuals were identified with confirmed incident RA. In multivariate models each increase in intake of 30 g fat fish (> or = 8 g fat/100 g fish) per day was associated with 49% reduction in the risk of RA (p = 0.06), whereas medium fat fish (3-7 g fat/100 g fish) was associated with significantly increased risk of RA. Intake of fruit and coffee was not associated with risk of RA. Furthermore, no associations were found between risk of RA and intake of a range of other dietary factors including long chain fatty acids, olive oil, vitamins A, E, C, D, zinc, selenium, iron, and meat. CONCLUSION: The limited number of patients who developed RA during followup of our large cohort prevented us from concluding that dietary factors are unimportant as risk factors for RA. It appears, however, that if dietary factors are important modifiers of RA risk, they must play a role more than a few years before clinical diagnosis.

Plasma enterolactone and breast cancer incidence by estrogen receptor status.

The phytoestrogen enterolactone has been hypothesized to prevent breast cancer. Because one of the biological effects of enterolactone is probably estrogenic, it is possible that the preventive effect on breast cancer differs with the estrogen receptor (ER) alpha status of the tumor. The objective of this study was to investigate whether high plasma levels of enterolactone are associated with breast cancer risk and whether the ERalpha status of the tumor influences this relation. The cohort study Diet, Cancer and Health included 29,785 women, ages 50 to 64 years, between 1993 and 1997. Information about diet and life-style factors was obtained by questionnaire, and blood was drawn from each participant. We matched 381 postmenopausal breast cancer cases to 381 controls and analyzed the concentration of enterolactone in plasma with a time-resolved fluoroimmunoassay. Associations between plasma concentrations of enterolactone and breast cancer were analyzed by logistic regression. The incidence rate ratio (IRR) for all breast cancer was 0.93 [95% confidence interval (CI), 0.86-1.01] per 20 nmol/L higher plasma concentration of enterolactone. For ERalpha-positive cancers (n=273) only a weak association was seen (IRR, 0.97; 95% CI, 0.88-1.06), whereas for ERalpha-negative cancers (n = 80; IRR, 0.71; 95% CI, 0.53-0.94) a protective effect was seen per 20 nmol/L higher plasma enterolactone. In accordance with earlier research, we found a tendency toward a lower risk for breast cancer with higher concentrations of enterolactone, which was restricted almost entirely to ERalpha-negative breast cancer.

Association of nut and seed intake with colorectal cancer risk in the European Prospective Investigation into Cancer and Nutrition.

A link between unsaturated fatty acids or phytonutrients and reduced risk of colorectal cancer has been suggested. However, the effects of higher intake of dietary sources of these nutrients, such as the nuts and seeds food group, are less clear. The objective of this study was to determine the effects of nut and seed intake on colorectal cancer risk within the European Prospective Investigation into Cancer and Nutrition study, a large prospective cohort study involving 10 European countries. Total nut and seed intake was determined from country-specific dietary questionnaires. The data set included 478,040 subjects (141,988 men, 336,052 women) with a total of 855 (327 men, 528 women) colon and 474 (215 men, 259 women) rectal cancer cases. A multivariate Cox proportional hazards model, stratified by center and controlled for fruit intake, dietary fiber, energy, height, weight, sex, age, physical activity, and smoking, was used. The data show no association between higher intake of nuts and seeds and risk of colorectal, colon, and rectal cancers in men and women combined, but a significant inverse association was observed in subgroup analyses for colon cancer in women at the highest (>6.2 g/d) versus the lowest (nonconsumers; hazard ratio, 0.69; 95% confidence interval, 0.50-0.95) category of intake and for the linear effect of log-transformed intake (hazard ratio, 0.89; 95% confidence interval, 0.80-0.98), with no associations in men. It is not evident from this data why there may be a stronger association in women or why it may be limited to the colon, suggesting that much further research is necessary.

Does insufficient adjustment for smoking explain the preventive effects of fruit and vegetables on lung cancer?

Recent reports have raised the question, whether the previously observed protective effects of high intake of fruit and vegetables on the risk of lung cancer were due to insufficient adjustment for smoking leading to residual confounding. Association of intake of fruit and vegetables on lung cancer risk was examined, using the Danish prospective cohort study, "Diet, Cancer and Health". Participants completed a food-frequency and lifestyle questionnaire, and age-standardized incidence rates and rate ratios were estimated for quartiles of dietary exposure. In 1993-2001, 247 out of the 54158 participants were diagnosed with lung cancer. The incidence rate of lung cancer was highest in the lowest quartile of intake of plant food (fruit, vegetables, legumes and potatoes) and the age-standardized rate ratio of lung cancer decreased significantly with increasing intake of plant food to 0.35 (95% CI, 0.27-0.45) but after control for smoking it was attenuated to 0.65 (95% CI, 0.45-0.93). The incidence rate differences of current smokers with high (> or = 400 g per day) and low (< 400 g per day) daily intake of plant food were independent of smoking intensity; assuming a true biological protective effect, 80-90 lung cancer cases per 100000 current smokers could be prevented in our cohort if all smokers had a high intake of plant food. The observed inverse association between high intakes of plant food seems chiefly to be a real protective effect, and not solely due to residual confounding.

Lifetime alcohol consumption and postmenopausal breast cancer rate in Denmark: a prospective cohort study.

Alcohol intake may be one of the few modifiable risk factors for breast cancer. In a prospective cohort of 29,875 women with 423 cases of breast cancer during 1993-2000, we examined the relationship between postmenopausal breast cancer incidence rate and alcohol consumption in different life periods. When alcohol intake during four age ranges, twenties, thirties, forties and fifties was evaluated, only the intake in the fifties increased the risk of breast cancer [rate ratio (RR)=1.12 (95% CI: 1.05-1.19)] per 10 g/d increase in alcohol intake. After adjustment for intake at study entry, this association was no longer present [RR=1.01 (95% CI: 0.91-1.13)]. The cumulative lifetime alcohol intake, adjusted for recent intake, showed no association with postmenopausal breast cancer risk. Recent alcohol intake, adjusted for the alcohol intake in the other life time periods, showed a significant association of RR=1.09 (95% CI: 1.00-1.18) per 10 g/d. There was no indication of a higher risk among women with early drinking start, nor did women who started to drink before their first birth have a higher risk than women who started to drink later in life. Our results suggest that baseline intake of alcohol is a more important determinant of postmenopausal breast cancer risk than earlier lifetime exposure.

Intake of vitamins A, C, and E from diet and supplements and breast cancer in postmenopausal women.

OBJECTIVE: The influence of the vitamins A, C, and E on breast cancer development has not been clarified. An effect of a vitamin per se implicates similar patterns for the effects of the vitamin from dietary and supplemental sources. We examined how the breast cancer incidence rate among postmenopausal women was related to intake of vitamins A, C, and E from diet and supplements. METHODS: Data was sampled as case-control nested within the Danish 'Diet, Cancer and Health' cohort. Data on vitamin intakes were collected at entry into the cohort by means of self-administered questionnaires. Women eligible for the nested case-control study were postmenopausal at entry into the cohort. The analyses were based on 418 cases of incident breast cancer and 394 controls (including two cases). RESULTS: Breast cancer was not significantly related to the intakes of vitamin A or E, whereas a monotonic dose-response relation was seen for the intake of vitamin C. The estimated rate ratio per 100 mg vitamin C was: 2.06 (95% CI: 1.45-2.91) for dietary intake and 1.06 (95% CI: 1.01-1.13) for supplemental intake. CONCLUSIONS: We found no evidence of an association between breast cancer and intake of vitamin A or E for postmenopausal women. For vitamin C we found an increase in breast cancer rate with increasing intake.

Fish intake is positively associated with breast cancer incidence rate.

Animal studies have, in general, been supportive of a protective effect of fish and fish (n-3) PUFA against breast cancer risk; but the epidemiologic evidence of such a relationship is limited. Case-control and cohort studies have rarely shown significant associations. The association between total fish intake and the effect of fat content and preparation method of the fish, in relation to the incidence rate ratios of breast cancer, were investigated among postmenopausal women. We also investigated the effect of fish intake with respect to estrogen receptor expression of breast cancer tumors. A total of 23,693 postmenopausal women from the prospective study "Diet, Cancer and Health" were included in the study. During follow-up, 424 women were diagnosed with breast cancer. The incidence rate ratio (IRR) and 95% CI per each additional 25 g of mean daily intake of fish were 1.13 (CI, 1.03-1.23). Analysis of fatty fish gave IRR of 1.11 (CI, 0.91-1.34), and the result for lean fish was 1.13 (CI, 0.99-1.29). When fish intake was stratified into three types of preparation methods, the IRR for fried fish was 1.09 (CI, 0.95-1.25), for boiled fish 1.09 (CI, 0.85-1.42), and for processed fish 1.12 (CI, 0.93-1.34). The IRR per additional 25 g of mean daily intake of fish was 1.14 (CI, 1.03-1.26) for estrogen receptor-positive (ER+) and 1.00 (CI, 0.81-1.24) for estrogen receptor-negative (ER-) breast cancer. In conclusion, this study showed that higher intakes of fish were significantly associated with higher incidence rates of breast cancer. The association was present only for development of ER+ breast cancer.

Fruits and vegetables intake differentially affects estrogen receptor negative and positive breast cancer incidence rates.

Despite intensive research, the evidence for a protective effect of fruits and vegetables on breast cancer risk remains inconclusive. Other risk factors for breast cancer seem to vary with the estrogen receptor status of the breast tumor, and it is thus possible that the inconsistent results regarding a preventive effect of fruits and vegetables are due to lack of controlling for estrogen receptor status. The objective of this study was to investigate the effect of fruit and vegetable intake on postmenopausal breast cancer and explore whether the estrogen receptor status of the tumor modifies this relation. Postmenopausal women (n = 23,798; aged 50-64 y) provided information about diet and established risk factors for breast cancer in the cohort "Diet, Cancer and Health." During follow-up, 425 cases were diagnosed with breast cancer. Associations between intake of fruits and vegetables and the breast cancer rate were analyzed using Cox's regression model. The association for all breast cancers was an incidence rate ratio (IRR) of 1.02 (95% CI, 0.98-1.06) per 100 g/d increment of total intake of fruits, vegetables and juice. For estrogen receptor-positive (ER(+)) breast cancer, a borderline significant increase in the rate was seen, IRR: 1.05 (95% CI, 1.00-1.10), whereas a preventive effect was seen for estrogen receptor-negative (ER(-)) breast cancers, IRR: 0.90 (95% CI, 0.81-0.99). In conclusion, we did not find the overall breast cancer rate to be associated with the intake of fruits and vegetables, but there seemed to be different effects for ER(+) and ER(-) breast cancer.

Intake of fruit and vegetables and the risk of ischemic stroke in a cohort of Danish men and women.

BACKGROUND: Previous studies have suggested that a high dietary intake of fruit and vegetables is associated with a reduced risk of ischemic stroke. The magnitude of the effect is uncertain, and only one study reported data on the intake of specific fruit and vegetables and the risk of stroke. OBJECTIVE: We examined whether the intake of fruit and vegetables is associated with a reduced risk of ischemic stroke, with particular attention paid to specific fruit and vegetables and subtypes of ischemic stroke. DESIGN: In a prospective cohort study of 54,506 men and women who were included in the Danish Diet, Cancer, and Health study from 1993 to 1997, estimated total intakes of fruit and vegetables (in g/d) were extracted from a semiquantitative food-frequency questionnaire completed at baseline. Data about subjects hospitalized with ischemic stroke were obtained from the Danish National Registry of Patients and were verified later by record reviews. The follow-up for ischemic stroke ended on the date of a first hospital admission for stroke or transient ischemic attack, the date of death or emigration, or the end of the study, whichever came first. RESULTS: We identified 266 cases of ischemic stroke involving hospitalization during 168,388 person-years of follow-up (median follow-up: 3.09 y; range: 0.02-5.10 y). After adjustment for potential confounders, persons in the top quintile of fruit and vegetable intake (median: 673 g/d) had a risk ratio of ischemic stroke of 0.72 (95% CI: 0.47, 1.12) relative to persons in the bottom quintile of intake (median: 147 g/d) (P for trend = 0.04). When comparing the top quintile with the bottom quintile, an inverse association was most evident for fruit intake (risk ratio: 0.60; 95% CI: 0.38, 0.95; P for trend = 0.02). Similar risk estimates were seen for most types of fruit and vegetables, although the risks were significant only for citrus fruit. CONCLUSION: An increased intake of fruit may reduce the risk of ischemic stroke.

Alcohol intake, drinking patterns and risk of postmenopausal breast cancer in Denmark: a prospective cohort study.

OBJECTIVE: The available epidemiological evidence indicates that drinking alcohol per se is associated with breast cancer. However, it has not been investigated how the breast cancer risk for a given total alcohol consumption depends on the drinking frequency. METHODS: Within the prospective study on 'Diet, Cancer and Health', we examined the relationship between breast cancer, intake of total alcohol and frequency of drinking among 23,778 postmenopausal women, among whom 425 cases of breast cancer accrued during a median follow-up of 4.8 years. RESULTS: The dose-response relationship between total alcohol intake and breast cancer showed an increase in the rate ratio of 1.10 per 10 g/day (95% CI: 1.04-1.16) with no evidence for differences by type of alcohol beverage. No interaction was found between drinking frequency and total alcohol intake in the risk of breast cancer (p = 0.40). CONCLUSIONS: The present study supports previous ones in showing a monotonic increase in the risk of breast cancer among postmenopausal women with increasing average daily intake of alcohol, and this relationship with alcohol intake did not depend on drinking frequency.