Dietary flavonoid intake and colorectal cancer risk in the European prospective investigation into cancer and nutrition (EPIC) cohort

Flavonoids have been shown to inhibit colon cancer cell proliferation in vitro and protect against colorectal carcinogenesis in animal models. However, epidemiological evidence on the potential role of flavonoid intake in colorectal cancer (CRC) development remains sparse and inconsistent. We evaluated the association between dietary intakes of total flavonoids and their subclasses and risk of development of CRC, within the European Prospective Investigation into Cancer and Nutrition (EPIC) study. A cohort of 477,312 adult men and women were recruited in 10 European countries. At baseline, dietary intakes of total flavonoids and individual subclasses were estimated using centre‐specific validated dietary questionnaires and composition data from the Phenol‐Explorer database. During an average of 11 years of follow‐up, 4,517 new cases of primary CRC were identified, of which 2,869 were colon (proximal = 1,298 and distal = 1,266) and 1,648 rectal tumours. No association was found between total flavonoid intake and the risk of overall CRC (HR for comparison of extreme quintiles 1.05, 95% CI 0.93–1.18; p‐trend = 0.58) or any CRC subtype. No association was also observed with any intake of individual flavonoid subclasses. Similar results were observed for flavonoid intake expressed as glycosides or aglycone equivalents. Intake of total flavonoids and flavonoid subclasses, as estimated from dietary questionnaires, did not show any association with risk of CRC development.     

Mediterranean dietary pattern and cancer risk in the EPIC cohort

Background:

Although several studies have investigated the association of the Mediterranean diet with overall mortality or risk of specific cancers, data on overall cancer risk are sparse.

Methods:

We examined the association between adherence to Mediterranean dietary pattern and overall cancer risk using data from the European Prospective Investigation Into Cancer and nutrition, a multi-centre prospective cohort study including 142 605 men and 335 873. Adherence to Mediterranean diet was examined using a score (range: 0–9) considering the combined intake of fruits and nuts, vegetables, legumes, cereals, lipids, fish, dairy products, meat products, and alcohol. Association with cancer incidence was assessed through Cox regression modelling, controlling for potential confounders.

Results:

In all, 9669 incident cancers in men and 21 062 in women were identified. A lower overall cancer risk was found among individuals with greater adherence to Mediterranean diet (hazard ratio=0.96, 95% CI 0.95–0.98) for a two-point increment of the Mediterranean diet score. The apparent inverse association was stronger for smoking-related cancers than for cancers not known to be related to tobacco (P (heterogeneity)=0.008). In all, 4.7% of cancers among men and 2.4% in women would be avoided in this population if study subjects had a greater adherence to Mediterranean dietary pattern.

Conclusion:

Greater adherence to a Mediterranean dietary pattern could reduce overall cancer risk.     

Yogurt consumption and risk of colorectal cancer in the Italian European prospective investigation into cancer and nutrition cohort

Fermented dairy products like yogurt have been suggested to protect against colorectal cancer (CRC). We conducted a prospective study on 45,241 (14,178 men; 31,063 women) volunteers of the EPIC-Italy cohort who completed a dietary questionnaire including specific questions on yogurt intake. During 12 years of follow-up, 289 volunteers were diagnosed with CRC. Hazard ratios (HRs) for the disease and 95% confidence intervals (CIs) were estimated by Cox proportional hazard models, stratified by dietary questionnaire and adjusted for energy intake and other potential confounders. Yogurt intake was inversely associated with CRC risk. For the energy-adjusted model, HR for CRC in the highest versus lowest tertile of yogurt intake was 0.62 (95% CI, 0.46-0.83). In the full model adjusted for energy, simple sugar, calcium, fiber, animal fat, alcohol and red meat intake, as well as body mass index, smoking, education and physical activity, HR was 0.65 (95% CI, 0.48-0.89) in the highest versus lowest tertile. The protective effect of yogurt was evident in the entire cohort, but was stronger in men, although there was no interaction of sex with the yogurt-CRC association (p(interaction) 0.20, fully adjusted model). In our prospective study, high yogurt intake was significantly associated with decreased CRC risk, suggesting that yogurt should be part of a diet to prevent the disease. Investigation of larger cohorts is necessary to reveal any residual confounding of the association of yogurt intake with CRC risk.     

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.     

Coffee consumption and the risk of colorectal cancer: a prospective cohort study in Japan

An inverse association between coffee consumption and the risk of colorectal cancer has been reported in several case-control studies, but results from prospective cohort studies have been inconclusive. We conducted a prospective cohort study among a Japanese population to clarify the association between coffee consumption and the risk of colorectal cancer incidence. We used data from the Miyagi Cohort Study for this analysis. Usable self-administered questionnaires about coffee consumption were returned from 22,836 men and 24,769 women, aged 40-64 years, with no previous history of cancer. We used the Cox proportional-hazard regression model to estimate hazard ratios and 95% confidence intervals. During 11.6 years of follow-up (425,303 person-years), we identified 457 cases of colorectal cancer. Coffee consumption was not associated with the incidence of colorectal, colon or rectal cancer. The multivariate-adjusted hazard ratio (95% confidence interval) of colorectal cancer incidence for 3 or more cups of coffee per day as compared with no consumption was 0.95 (0.65-1.39) for men and women (p for trend = 0.55), 0.91 (0.56-1.46) for men (p for trend = 0.53) and 1.16 (0.60-2.23) for women (p for trend = 0.996). Coffee consumption was also not associated with incidence of either proximal or distal colon cancer. We conclude that coffee consumption is not associated with the incidence risk of colorectal cancer in the general population in Japan.     

Dietary and biomarker estimates of fatty acids and risk of colorectal cancer

The associations between intake of or circulating fatty acids and risk of colorectal cancer (CRC) are unclear. We examined prospectively the associations between dietary or biomarker fatty acids and CRC. For 41,514 men and women, aged 40–69 years, baseline (1990–94) dietary intakes of fatty acids were estimated using a food frequency questionnaire and plasma phospholipid (PPL) fatty acids were measured for 4,205 participants including 395 CRC cases, according to a case‐cohort design. Hazard ratios were computed using Cox regression adjusting for education, alcohol intake, smoking status, physical activity and total energy intake; and stratified for gender, ethnicity and family history of cancer, with age as the time scale. We assessed the heterogeneity of associations with colon and rectal cancers. PPL saturated fatty acids (SFAs) were positively associated with CRC risk, while total n‐3 polyunsaturated fatty acids (PUFA) and long chain marine n‐3 PUFAs showed inverse associations, significant only for 22:5 n‐3. No significant associations were observed for dietary fatty acid intakes but positive associations with CRC of borderline significance were seen for both dietary and PPL linoleic acid. Positive associations with dietary palmitic acid (16:0), MUFAs and n‐6 PUFAs were seen for rectal but not colon cancers. PPL 22:6 n‐3 was inversely associated with rectal cancer. Limiting intakes of SFAs and MUFAs could be assisted by following existing guidelines to limit red and processed meats which are important sources in the Australian diet. Our observations regarding linoleic acid should be examined further.     

Coffee consumption and risk of colorectal cancer in a population-based prospective cohort of Japanese men and women

We prospectively examined the association between coffee consumption and the risk of developing colorectal cancer in a large population-based cohort study (the JPHC Study) of Japanese men and women. Data were analyzed from a population-based cohort of 96,162 subjects (46,023 men and 50,139 women). A total of 1,163 incident colorectal cancers were identified during the follow-up period, including 763 cases of colon cancer and 400 of rectal cancer. We observed a significant inverse association between coffee consumption and the risk of developing invasive colon cancer among women. Compared with those who almost never consumed coffee, women who regularly consumed 3 or more cups of coffee per day had a RR of 0.44 (95% CI = 0.19-1.04; p for trend = 0.04) after adjustment for potential confounding factors. However, no significant association was found for rectal cancer in women. In men, no significant decrease was observed in any colorectal cancer site. Further, additional analyses on the association of green tea consumption with colorectal cancer risk found no significant association in men or women. These findings suggest that coffee consumption may lower the risk of colon cancer among Japanese women.     

Dairy product consumption and risk of colorectal cancer in an older mediterranean population at high cardiovascular risk

Prospective studies have reported an inverse association between the consumption of total dairy products and milk and the risk of colorectal cancer (CRC). Nonetheless, there is little and inconsistent evidence regarding subtypes of dairy product and CRC risk. We assessed the associations between the consumption of total dairy products, their different subtypes and CRC risk in older Mediterranean individuals at high cardiovascular risk. We analyzed data from 7,216 men and women (55–80 years) without CRC at baseline from the PREvención con DIeta MEDiterránea study. Individuals were recruited between 2003 and 2009 and followed up until December 2012. At baseline and yearly thereafter, consumption of total and specific dairy products was assessed using a validated 137‐item food‐frequency questionnaire. Cox proportional hazards ratios (HRs) of CRC incidence were estimated for tertiles of mean consumption of dairy products during the follow‐up. During a median [interquartile range] follow‐up of 6.0 [4.4–7.3] years, we documented 101 incident CRC cases. In the multivariable‐adjusted models, HRs and 95% confidence intervals (CIs) of CRC for the comparison of extreme tertiles of total dairy product and low‐fat milk consumption were 0.55 (95% CI: 0.31–0.99; p‐trend = 0.037) and 0.54 (95% CI: 0.32–0.92; p‐trend = 0.022), respectively. No significant associations with other dairy products (whole‐fat and low‐fat dairy products; total, low‐fat and whole‐fat yogurt; cheese; total, low‐fat and whole‐fat milk; concentrated full‐fat dairy products, sugar‐enriched dairy products and fermented dairy products) were found. A high consumption of total dairy products and low‐fat milk was significantly associated with a reduced CRC risk.     

The risk of colorectal cancer is associated with the frequency of meat consumption in a population-based cohort in Korea

Objective: To date, there have been few prospective cohort studies that have investigated the association between meat consumption and the risk of colorectal cancer (CRC) in Asian countries. A large, population-based cohort study was conducted to assess the effect of the frequency of meat consumption on the risk of CRC in Korean adults. Methods: The participants were Korean government employees, school faculty members, and their unemployed dependents, aged 30–80 years, who underwent health examinations between 1996 and 1997. In 2003, information on CRC incidence was obtained during the 6–7 year follow-up period. The final data analysis included 2,248,129 study subjects. The hazard ratio (HR) and 95% confidence interval (CI) of the HR were estimated using the Cox proportional hazards regression model. Results: During the follow-up period, CRC occurred in 4,501 men and 1,943 women (64.19 and 36.34 for age-standardized incidence rates per 100,000 person-years, respectively). In the total population, the estimated HRs and 95% CI for meat consumption of 2–3 times per week and more than 4 times per week compared with consumption of less than once per week were 1.06 (1.01–1.12) and 1.23 (1.13–1.35), respectively. In men only and women only groups, the HRs (95% CI) for consumption of more than 4 times per week compared with consumption of less than once per week were 1.13 (1.02–1.26) and 1.42 (1.21–1.66), respectively. Conclusion: The present findings suggest that frequency of meat consumption is positively associated with the risk of CRC.     

Sugar intake and colorectal cancer risk: A prospective Japanese cohort study

The influence of sugar consumption on the risk of colorectal cancer (CRC) remains controversial. Prospective cohort studies focusing on total and specific types of sugar intake among the Asian population who have different patterns of sugar intake sources than American and European populations are scarce. We intended to examine the association of sugar intake with CRC risk among middle-aged adults in a Japanese large-scale population-based cohort study. The participants (42,405 men and 48,600 women) who were 45–74 years old and answered the questionnaire in 1995–1999 in the Japan Public Health Center-based Prospective Study were followed up until December 2013. Total sugars, total fructose, and specific types of sugar intake were estimated using a validated 147-item food frequency questionnaire and divided into quintiles (Q1–Q5). We used Cox proportional hazard regression models adjusted for potential confounders to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). During the follow-up, 2118 CRC cases (1226 men and 892 women) were identified. We did not observe any clear association between all types of sugar intake and an increased risk of CRC. Analyses by tumor sites yielded a positive association of total sugar consumption with rectal cancer in women (1.75 [1.07–2.87] for Q1 vs. Q5; p _{linear trend} = 0.03), but no statistically significant trend was detected among men. Sugar intake was not associated with CRC risk in middle-aged Japanese adults. However, for rectal cancer, the probability of an increased risk among women with a higher total sugar intake cannot be excluded.     

Conformity to traditional Mediterranean diet and cancer incidence: the Greek EPIC cohort

Adherence to traditional Mediterranean diet (MD) has been reported to be inversely associated with total, as well as cardiovascular, mortality. We have examined the relation between degree of such adherence and incidence of cancer overall in a general population sample of 25 623 participants (10 582 men, 15 041 women) of the Greek segment of the European Prospective Investigation into Cancer and nutrition (EPIC). All subjects completed a validated, interviewer-administered, semi-quantitative food-frequency questionnaire at enrolment. Degree of adherence to the traditional MD was assessed through a 10-point scale (0 minimal; 9 maximal) that incorporated key dietary characteristics. During a median follow-up of 7.9 years and 188 042 total person-years, 851 medically confirmed incident cancer cases (421 men, 430 women) were recorded. Using proportional hazards regression with adjustment for potential confounders, we found that a higher degree of MD adherence was associated with lower overall cancer incidence. A two-point increase in the score corresponded to a 12% reduction in cancer incidence (adjusted hazard ratio, 0.88 (95% confidence interval 0.80, 0.95)). The association was exposure-dependent and stronger among women. This inverse association with MD adherence was considerably stronger than that predicted on the basis of the associations of the individual components of this diet and points to the value of analysing dietary patterns in cancer studies.     

Dietary fiber intake and subsequent risk of colorectal cancer: the Japan Public Health Center-based prospective study

Results on the association of dietary fiber intake with colorectal cancer risk were inconsistent among previous large prospective studies, but studies in non-Western populations are lacking. Consequently, the authors investigated the association between dietary fiber intake and the subsequent risk of colorectal cancer in a prospective cohort study of a Japanese population. Dietary fiber intake was estimated from food-frequency questionnaires comprising 44 or 52 items at the baseline survey and 138 food items at a 5-year follow-up survey. The authors identified 907 cases of colorectal adenocarcinoma diagnosed pathologically in 86,412 subjects during a 10-year follow-up from the baseline survey. After the 5-year follow-up survey, 522 cases were identified in 78,326 subjects during a 5.8-year follow-up. The authors estimated the multivariate-adjusted hazard ratios of colorectal cancer for dietary fiber intake using Cox's proportional hazards model. The authors found no statistically significant association between dietary fiber intake and colorectal cancer in analyses using data either from the baseline survey or from the 5-year follow-up survey. However, the risk of only the lowest quintile was high, compared with the second to the fifth quintiles. Furthermore, the lowest subtertile in the lowest quintile was associated with an increased risk in women (hazard ratio(Sub1 vs. Q5), 2.3; 95% confidence interval, 1.0-5.2). In conclusion, although a minor effect cannot be ruled out, the results did not support a hypothesis of a dose-dependent protective effect of dietary fiber intake against colorectal cancer.     

Lifetime and baseline alcohol intake and risk of colon and rectal cancers in the European prospective investigation into cancer and nutrition (EPIC)

Alcohol consumption may be associated with risk of colorectal cancer (CRC), but the epidemiological evidence for an association with specific anatomical subsites, types of alcoholic beverages and current vs. lifetime alcohol intake is inconsistent. Within the European Prospective Investigation into Cancer and Nutrition (EPIC), 478,732 study subjects free of cancer at enrolment between 1992 and 2000 were followed up for an average of 6.2 years, during which 1,833 CRC cases were observed. Detailed information on consumption of alcoholic beverages at baseline (all cases) and during lifetime (1,447 CRC cases, 69% of the cohort) was collected from questionnaires. Cox proportional hazard models were used to examine the alcohol-CRC association. After adjustment for potential confounding factors, lifetime alcohol intake was significantly positively associated to CRC risk (hazard ratio, HR=1.08, 95%CI=1.04-1.12 for 15 g/day increase), with higher cancer risks observed in the rectum (HR=1.12, 95%CI=1.06-1.18) than distal colon (HR=1.08, 95%CI=1.01-1.16), and proximal colon (HR=1.02, 95%CI=0.92-1.12). Similar results were observed for baseline alcohol intake. When assessed by alcoholic beverages at baseline, the CRC risk for beer (HR=1.38, 95%CI=1.08-1.77 for 20-39.9 vs. 0.1-2.9 g/day) was higher than wine (HR=1.21, 95%CI=1.02-1.44), although the two risk estimates were not significantly different from each other. Higher HRs for baseline alcohol were observed for low levels of folate intake (1.13, 95%CI=1.06-1.20 for 15 g/day increase) compared to high folate intake (1.03, 95%CI=0.98-1.09). In this large European cohort, both lifetime and baseline alcohol consumption increase colon and rectum cancer risk, with more apparent risk increases for alcohol intakes greater than 30 g/day.     

No association between fruit or vegetable consumption and the risk of colorectal cancer in Japan

In a pooled analysis of two prospective studies with 88,658 Japanese men and women, fruit and vegetable consumptions, were not associated with a lower risk of colorectal cancer (705 cases); multivariate relative risk (95% confidence interval) for the highest vs the lowest quartile of intake being 0.92 (0.70-1.19) and 1.00 (0.79-1.27), respectively.     

Diet and risk of colorectal cancer in a cohort of Finnish men

Objectives: Based on previous epidemiological studies, high fat and meat consumption may increase and fiber, calcium, and vegetable consumption may decrease the risk of colorectal cancer. We sought to address these hypotheses in a male Finnish cohort.Methods: We analyzed data from the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study (ATBC Study) where 27, 111 male smokers completed a validated dietary questionnaire at baseline. After an average of 8 years of follow-up, we documented 185 cases of colorectal cancer. The analyses were carried out using the Cox proportional hazards model.Results: The relative risk (RR) for men in the highest quartile of calcium intake compared with men in the lowest quartile was 0.6 (95% CI 0.4–0.9, p for trend 0.04). Likewise, the intake of milk protein and the consumption of milk products was inversely associated with risk of colorectal cancer. However, intake of dietary fiber was not associated with risk, nor was fat intake. Consumption of meat or different types of meat, and fried meat, fruits or vegetables were not associated with risk.Conclusions: In this cohort of men consuming a diet high in fat, meat, and fiber and low in vegetables, high calcium intake was associated with lowered risk of colorectal cancer.     

Bowel movement frequency and risk of colorectal cancer in a large cohort study of Japanese men and women

The relationship between bowel movement (BM) frequency and the risk of colorectal cancer was examined in a large cohort of 25 731 men and 37 198 women living in 24 communities in Japan. At enrolment, each participant completed a self-administrated questionnaire on BM frequency and laxative use. Incidence rate ratios (IRR) with 95% confidence intervals (CI) were estimated using Cox's proportional-hazard model. During the follow-up period (average length 7.6 years), 649 cases of colorectal cancer, including 429 cases of colon cancer, were identified. Among women, subjects who reported a BM every 2-3 days had the lowest risk of developing colorectal (IRR=0.71, 95% CI=0.52-0.97) and colon cancer (IRR=0.70, 95% CI=0.49-1.00), whereas those reporting a BM every 6 days or less had an increased risk of developing colorectal (IRR=2.47, 95% CI=1.01-6.01) and colon cancer (IRR=2.52, 95% CI=0.93-6.82) compared with those reporting >or=1 BM per day. A similar, but nonsignificant, association between the frequency of BM and cancer risk was observed in men. There was no association between colorectal or colon cancer risk and laxative use. Regulating BM frequency might therefore have a role in the prevention of colorectal cancer.     

Fish consumption and the risk of colorectal cancer: the Ohsaki Cohort Study

Background:

Evidence from laboratory and animal studies suggests that high fish consumption may reduce the risk of colorectal cancer, but the results of studies in humans have been inconsistent. The objective of this study was to prospectively examine the association between fish consumption and the risk of colorectal cancer incidence in Japan, where fish is widely consumed.

Methods:

We analysed data from 39 498 men and women registered in the Ohsaki National Health Insurance Cohort Study who were 40–79 years old and free of cancer at the baseline. Fish consumption was assessed at the baseline using a self-administered food frequency questionnaire.

Results:

During 9 years of follow-up, we identified 566 incident cases of colorectal cancer (379 men and 187 women). The hazard ratios and 95% confidence intervals (CIs) for colorectal cancer incidence in the highest quartile of fish consumption compared with the lowest quartile were 1.07 (95% CIs; 0.78–1.46, P-trend=0.43) for men, and 0.96 (95% CIs; 0.61–1.53, P-trend=0.69) for women.

Conclusion:

The results of this prospective cohort study revealed no association between fish consumption and the risk of colorectal cancer.     

Long-term aspirin use and colorectal cancer risk: a cohort study in Sweden

In a prospective cohort study of 74 250 Swedish women and men, with 7.2 years of follow-up and 705 incident colorectal cancer cases, long duration of aspirin use (>20 years) was associated with a reduced risk of colorectal cancer (multivariate rate ratio: 0.65; 95% confidence interval: 0.45-0.94). Aspirin use for a shorter period was not associated with risk.     

Mediterranean diet adherence and risk of postmenopausal breast cancer: results of a cohort study and meta‐analysis

The Mediterranean Diet (MD) has been associated with reduced mortality and risk of cardiovascular diseases, but there is only limited evidence on cancer. We investigated the relationship between adherence to MD and risk of postmenopausal breast cancer (and estrogen/progesterone receptor subtypes, ER/PR). In the Netherlands Cohort Study, 62,573 women aged 55–69 years provided information on dietary and lifestyle habits in 1986. Follow‐up for cancer incidence until 2007 (20.3 years) consisted of record linkages with the Netherlands Cancer Registry and the Dutch Pathology Registry PALGA. Adherence to MD was estimated through the alternate Mediterranean Diet Score excluding alcohol. Multivariate case–cohort analyses were based on 2,321 incident breast cancer cases and 1,665 subcohort members with complete data on diet and potential confounders. We also conducted meta‐analyses of our results with those of other published cohort studies. We found a statistically significant inverse association between MD adherence and risk of ER negative (ER?) breast cancer, with a hazard ratio of 0.60 (95% Confidence Interval, 0.39–0.93) for high versus low MD adherence (p _trend = 0.032). MD adherence showed only nonsignificant weak inverse associations with ER positive (ER+) or total breast cancer risk. In meta‐analyses, summary HRs for high versus low MD adherence were 0.94 for total postmenopausal breast cancer, 0.98 for ER+, 0.73 for ER? and 0.77 for ER ? PR? breast cancer. Our findings support an inverse association between MD adherence and, particularly, receptor negative breast cancer. This may have important implications for prevention because of the poorer prognosis of these breast cancer subtypes.