Meat, fish and fat intake in relation to subsite-specific risk of colorectal cancer: The Fukuoka Colorectal Cancer Study

High intake of red meat has been associated with increased risk of colorectal cancer in Western countries. There has been much interest in the role of n-3 polyunsaturated fatty acids (PUFA) in colorectal cancer prevention, but epidemiological findings are limited and inconsistent. The objective of our study was to examine associations of meat, fish and fat intake with risk of colorectal cancer, paying particular attention to the subsite within the colorectum. Data were from the Fukuoka Colorectal Cancer Study, a population-based case-control study, covering 782 cases and 793 controls. Diet was assessed by interview, using newly developed personal-computer software for registering semiquantitative food frequencies. The intake of beef/pork, processed meat, total fat, saturated fat or n-6 PUFA showed no clear association with the overall or subsite-specific risk of colorectal cancer. There was an almost significant inverse association between n-3 PUFA and the risk of colorectal cancer; the covariate-adjusted odds ratio for the highest (median 3.94 g/day) versus lowest (median 1.99 g/day) quintile of energy-adjusted intake was 0.74 (95% confidence interval 0.52-1.06, trend P=0.050). The consumption of fish and fish products was similarly inversely related to the risk although the association was not statistically significant. These associations were more evident for distal colon cancer; adjusted odds ratio for the highest versus lowest quintile of n-3 PUFA intake was 0.56 (95% confidence interval 0.34-0.92, trend P=0.02). Our findings do not support the hypothesis that consumption of red meat increases colorectal cancer risk but do suggest that high intake of fish may decrease the risk, particularly of distal colon cancer.     

Intake of n-3 and n-6 polyunsaturated fatty acids and development of colorectal cancer by subsite: Japan Public Health Center-based prospective study

To date, epidemiologic studies investigating intake of n-3 and n-6 polyunsaturated fatty acids and risk of colorectal cancer are limited, and results remain inconsistent. This is the first prospective study to show the association by subsite (proximal colon, distal colon, rectum). To clarify the role of n-3 and n-6 polyunsaturated fatty acids intake in colon carcinogenesis, we conducted a large, population-based prospective study, characterized by high fish consumption and a wide range of n-3 polyunsaturated fatty acids intakes. Subjects were followed from response to a lifestyle questionnaire in 1995-1999 through 2006. During 827,833 person-years of follow-up (average 9.3 years), we identified 1,268 new colorectal cancer cases (521 colon and 253 rectal for men; 350 colon and 144 rectal for women). Compared to the lowest quintile, the relative risk and 95% confidence interval of developing cancer among the fifth quintile of marine n-3 polyunsaturated fatty acids intake were 0.60 and 0.31-1.14, respectively (p for trend = 0.04) in the colon in women and 0.35 and 0.14-0.88 (p for trend = 0.05) and 1.82 and 0.79-4.20 (p for trend = 0.16) in the proximal and distal colon, respectively, in men. For rectal cancer, the dose response for marine n-3 polyunsaturated fatty acids s was unclear; rather, we observed U-shaped associations in men and women. We found no evidence that n-6 polyunsaturated fatty acids increases or the n-3/n-6 ratio decreases the risk of colorectal cancer. Our results suggest that intake of marine n-3 polyunsaturated fatty acids may be inversely related to the risk of cancer in the proximal site of the large bowel.     

A 22-year Prospective Study of Fish, n-3 Fatty Acid Intake, and Colorectal Cancer Risk in Men.

BACKGROUND: Fish is the main dietary source of long-chain n-3 fatty acids, which have been suggested to play a protective role in colorectal cancer development in laboratory and animal studies. Human studies have not shown consistent results. We examined the association between intakes of fish and n-3 fatty acids from fish and colorectal cancer risk in men enrolled in the Physicians' Health Study. METHODS: The Physicians' Health Study began as a randomized trial to examine the effect of aspirin and beta-carotene supplementation on cancer and cardiovascular disease. Fish intake was assessed at the 12-month follow-up with an abbreviated food-frequency questionnaire. Cox proportional hazards models were used to estimate multivariate relative risks for colorectal cancer for the categories of fish intake and quartiles of n-3 fatty acid intake. RESULTS: During 22 years of follow-up, 500 men had a confirmed diagnosis of colorectal cancer. Fish intake was inversely associated with colorectal cancer risk [multivariate relative risk (95% confidence interval) for highest versus lowest category, 0.60 (0.40-0.91); P trend = 0.01]. The inverse association was observed for both colon and rectal cancers. Our findings for n-3 fatty acids were similar to those for fish; the multivariate relative risk (95% confidence interval) of total colorectal cancer for the highest versus lowest quartile of n-3 fatty acids was 0.74 (0.57-0.95; P trend = 0.01). CONCLUSIONS: Our results from this long-term prospective study suggest that intakes of fish and long-chain n-3 fatty acids from fish may decrease the risk for colorectal cancer.     

Biomarkers of dietary fatty acid intake and the risk of breast cancer: a meta-analysis

The use of the fatty acid composition of adipose tissue, erythrocyte membranes, serum and plasma as biological markers of fatty acid intake was recently introduced in epidemiological studies. The biomarkers of fatty acid intake have the advantage of providing quantitative measurement independent of energy intake and of the subject's memory. We performed a meta-analysis of published results of epidemiological studies of the composition of fatty acids in biological samples and breast cancer risk. The analysis was based on 3 cohort and 7 case-control studies including 2,031 cases and 2,334 controls. The summary statistic used was the average of the relative risk estimated for each level of the fatty acid on study, weighted by the inverse of its variance. Random effect models were assumed when the test for heterogeneity was significant. Overall relative risks were estimated for studies including pre- and post-menopausal breast cancer and separately for post-menopausal women. In cohort studies, a significant protective effect was found for total n-3 polyunsaturated fatty acids, while total monounsaturated fatty acids, oleic acid (C18:1 n-9c) and palmitic acid (C16:0) were significantly associated with an increase of breast cancer risk. Total saturated fatty acids were significantly associated with breast cancer risk in cohort studies only in postmenopausal women. For case-control studies, the only finding was for alpha linolenic acid (C18:3, n-3), which showed an inverse association bordering on statistical significance. The findings of cohort studies fit well with hypotheses derived from experimental animal studies. More epidemiological cohort studies that integrate biological markers of dietary fatty acid intake are needed in order to determine the contribution of different types of fatty acids in the etiology of breast cancer.     

Prostate cancer risk and consumption of fish oils: a dietary biomarker-based case-control study

Experimental studies suggest that the risk of prostate cancer is reduced with the intake of long-chain n-3 polyunsaturated fatty acids derived from marine foods, such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). However, few human studies have been conducted due to difficulties in assessing the dietary intake of these fatty acids. The authors examined the relationship between prostate cancer risk and EPA and DHA in erythrocyte biomarkers in a population-based case-control study in Auckland, New Zealand during 1996-1997 involving 317 prostate cancer cases and 480 age-matched community controls. Reduced prostate cancer risk was associated with high erythrocyte phosphatidylcholine levels of EPA (multivariate relative risk = 0.59; 95% confidence interval 0.37-0.95, upper vs lowest quartile) and DHA (multivariate relative risk = 0.62; 95% confidence interval 0.39-0.98, upper vs lowest quartile). These analyses support evidence from in vitro experiments for a reduced risk of prostate cancer associated with dietary fish oils, possibly acting via inhibition of arachidonic acid-derived eicosanoid biosynthesis.     

Risk of colorectal cancer is linked to erythrocyte compositions of fatty acids as biomarkers for dietary intakes of fish, fat, and fatty acids.

Consumption of fish rich in n-3 polyunsaturated fatty acids (PUFAs), such as docosahexaenoic acid, is suggested to reduce colorectal cancer risk through inhibition of the arachidonic acid (AA) cascade related to tumorigenesis and cell proliferation. High intake of saturated fatty acids (SFAs) may increase the risk. To examine associations between colorectal cancer risk and fatty acid compositions in erythrocyte membranes, as biomarkers for dietary intakes of fish, fat, and fatty acids, we conducted a case-control study with 74 incident cases and 221 noncancer controls (matched by age, sex, and season of sample collection). Erythrocyte fatty acids were measured using an accelerated solvent extraction and a gas-liquid chromatography. Colorectal cancer had no association with dietary intakes of meat, fish, fat, and fatty acids. However, the risk was inversely associated with erythrocyte compositions of docosahexaenoic acid, AA, and PUFAs [the highest to the lowest tertile, odds ratios, 0.36, 0.42, and 0.15; 95% confidence intervals, 0.14-0.93, 0.18-0.95, and 0.05-0.46; P(trend) < 0.05, respectively] and positively with those of palmitic acid, SFAs, and the ratio of SFAs/PUFAs (odds ratios, 6.46, 8.20, and 9.45; 95% confidence intervals, 2.41-17.26, 2.86-23.52, and 2.84-31.43; P(trend) < 0.005, respectively). In conclusion, we could clearly show decreased and increased risks for colorectal cancer related to PUFAs and SFAs compositions in erythrocyte membranes, respectively, but further research is needed to investigate the discrepancy between our findings and the generally accepted role of the AA cascade.     

Genetic variability in prostaglandin synthesis, fish intake and risk of colorectal polyps

Dietary polyunsaturated fatty acids (PUFAs) can be converted to prostaglandins and leukotrienes. Metabolism of omega-6 (n-6) PUFAs results in the production of pro-inflammatory mediators whereas downstream products of omega-3 (n-3) PUFAs have lower inflammatory activity. Elevated n-3 PUFA intake from dietary fish may be associated with lower risk of colorectal neoplasia among those with genetic variants resulting in higher levels of pro-inflammatory mediators. We investigated interactions between dietary fish intake and polymorphisms in cyclooxygenase (COX)-1, COX-2, ALOX5 and PGIS in a case-control study of adenomas (N = 522), hyperplastic polyps (N = 194) and polyp-free controls (N = 626). Polyp risk did not differ by fish intake. A suggested interaction with fish intake was observed for COX-1 P17L. Among those who were homozygous wild type, increasing fish intake was associated with a modestly reduced risk of adenoma, whereas among those with at least one variant allele, the reverse trend was observed (p-interaction = 0.08). The interaction was statistically significant when non-steroidal anti-inflammatory drug (NSAID) use was also taken into account: among those with COX-1 17PP genotypes, high fish intake and regular NSAID use was associated with a decreased risk compared with low fish intake and low NSAID use (odds ratio = 0.60, 95% confidence interval 0.33-1.09). The opposite association was observed among those with COX-1 17PL or LL genotypes (p-interaction = 0.04). Our results suggest that the effects of dietary n-3 PUFA intake and NSAID use may differ by genetic variation in COX-1.     

Opposing effects of dietary n-3 and n-6 fatty acids on mammary carcinogenesis: The Singapore Chinese Health Study

We investigated the effects of individual fatty acids on breast cancer in a prospective study of 35,298 Singapore Chinese women aged 45-74 years, who were enrolled during April 1993 to December 1998 (The Singapore Chinese Health Study). At recruitment, each study subject was administered, in-person, a validated, semiquantitative food frequency questionnaire consisting of 165 food and beverage items. As of December 31, 2000, 314 incident cases of breast cancer had occurred. We used the Cox regression methods to examine individual fatty acids in relation to breast cancer risk, with adjustment for age at baseline interview, year of interview, dialect group, level of education, daily alcohol drinking, number of live births, age when menstrual periods became regular, and family history of breast cancer. Consumption of saturated, monounsaturated or polyunsaturated fat overall was unrelated to risk. On the other hand, high levels of dietary n-3 fatty acids from fish/shellfish (marine n-3 fatty acids) were significantly associated with reduced risk. Relative to the lowest quartile of intake, individuals in the higher three quartiles exhibited a 26% reduction in risk (relative risk (RR)=0.74, 95% confidence interval (CI)=0.58, 0.94)); RRs were similar across the top three quartiles of intake (0.75, 0.75, 0.72, respectively). Overall, there was no association between n-6 fatty acids and breast cancer risk. However, among subjects who consumed low levels of marine n-3 fatty acids (lowest quartile of intake), a statistically significant increase in risk was observed in individuals belonging to the highest vs the lowest quartile of n-6 fatty acid consumption (RR=1.87, 95% CI=1.06-3.27); the corresponding RR for advanced breast cancer was 2.45 (95% CI=1.20-4.97, P for trend=0.01). To our knowledge, these are the first prospective findings linking the intake of marine n-3 fatty acids to breast cancer protection.     

Mediterranean diet and cancer risk.

Various aspects of the Mediterranean diet are considered favourable with regard to cancer risk. These aspects were analysed using data from a series of case-control studies conducted in northern Italy between 1983 and 2001 on over 12,000 cases of 20 cancer sites and 10,000 controls. For most epithelial cancers, the risk decreased with increasing vegetable and fruit consumption, with odds ratios (OR) between 0.3 and 0.7 for the highest versus the lowest tertile. Subjects reporting frequent red meat intake showed ORs above unity for several common neoplasms. Conversely, fish (and consequently, n-3 fatty acids) tended to be another favourable dietary indicator. Wholegrain food intake was related to reduced risk of several types of cancer, particularly of the upper digestive tract, probably on account of its high fibre content. Fibres were in fact found to be protective with regard to colorectal and other selected cancers. In contrast to wholegrain, refined grain intake, and consequently glycaemic load, was associated with an increased risk of different types of cancer, including those of the upper digestive tract, colorectum, breast and endometrium. These results thus suggest that a low-risk diet for cancer entails increasing vegetables and fruit, reducing meat, but also refined carbohydrate consumption. Furthermore, olive oil and other unsaturated fats, which may be a unique common characteristic of the Mediterranean diet, should be preferred to animal and saturated fats. A score summarizing the major characteristics of the Mediterranean diet was inversely and consistently related to the risk of selected cancer sites. Regular consumption of pizza, one of the most typical Italian foods, showed a reduced risk of digestive tract cancers. Pizza could however simply be an indicator of a typical Italian diet.     

Unsaturated fatty acids intake and breast cancer risk: epidemiological data review

The relationship between fatty acids and breast cancer has been debated for long, because of the high frequency of breast cancer and the contradictory results from the numerous studies devoted to this issue. The present review includes case-control and prospective studies, according to specified methodological criteria, which estimated the exposure to monounsaturated fatty acids (MUFA) and n-6 and n-3 polyunsaturated fatty acids (PUFA) using dietary questionnaires or markers (plasma, erythrocytes, adipose tissue). The relationship between MUFA intake and breast cancer risk seems to depend on the contributing food : neutral or beneficial for vegetable oil, rather deleterious for animal products. Contrary to data from animal experiments, human studies do not show an increase of breast cancer risk with n-6 PUFA intake. Estimating the risk associated with alpha-linolenic acid appears difficult due to the incompleteness of food composition tables and studies on biomarkers remain few. The same applies to long-chain n-3 PUFA despite the suggestion of a decrease in risk, in agreement with animal studies. However, it is difficult in human to disentangle the effect of nutrient intake from that of contributing foods or even nutritional profile.     

Breast cancer risk and erythrocyte compositions of n-3 highly unsaturated fatty acids in Japanese

Dietary intake of fish rich in n-3 highly unsaturated fatty acids (HUFAs), such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), has been proposed to decrease cancer risk. In contrast to results from laboratory studies, however, protective effects for breast cancer have proved equivocal in epidemiological studies. In the present case-control study, we examined associations between breast cancer risk and fatty acid compositions in erythrocyte membranes as biomarkers for those intakes. Dietary information and blood samples were collected from 103 incident breast cancer cases and 309 non-cancer controls (matched by age and season) and erythrocyte fatty acids were measured using accelerated solvent extraction and gas-liquid chromatography. Dietary intake of n-3 HUFAs demonstrated a negative association with risk (the highest to the lowest tertile, odds ratio (OR), 0.51; 95% confidence interval (CI), 0.27-0.98; p(trend)<0.05), but there was no association with those of saturated fatty acids (SFAs) and meat. Moreover, risk was inversely associated with erythrocyte compositions of EPA (OR, 0.27; 95% CI, 0.14-0.53; p(trend)<0.0001), DHA (OR, 0.06; 95% CI, 0.02-0.16; p(trend)<0.0001) and n-3 HUFAs (OR, 0.11; 95% CI, 0.05-0.24; p(trend)<0.0001), and positively with that of SFAs (OR, 12.29; 95% CI, 4.94-30.57; p(trend)<0.0001) and the ratio of SFAs/n-3 HUFAs (OR, 14.65; 95% CI, 5.67-37.82; p(trend)<0.0001). In conclusion, we showed that erythrocyte compositions of specific fatty acids derived from fish intake, as biomarkers, are associated with lower risk of breast cancer, but further studies are needed to investigate mechanisms linked to the etiology.     

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.     

N-3 and N-6 fatty acids in breast adipose tissue and relative risk of breast cancer in a case-control study in Tours, France

Experimental studies have indicated that n-3 fatty acids, including alpha-linolenic acid (18:3 n-3) and long-chain n-3 polyunsaturated fatty acids inhibit mammary tumor growth and metastasis. Earlier epidemiological studies have given inconclusive results about a potential protective effect of dietary n-3 polyunsaturated fatty acids on breast cancer risk, possibly because of methodological issues inherent to nutritional epidemiology. To evaluate the hypothesis that n-3 fatty acids protect against breast cancer, we examined the fatty acid composition in adipose tissue from 241 patients with invasive, nonmetastatic breast carcinoma and from 88 patients with benign breast disease, in a case-control study in Tours, central France. Fatty acid composition in breast adipose tissue was used as a qualitative biomarker of past dietary intake of fatty acids. Biopsies of adipose tissue were obtained at the time of surgery. Individual fatty acids were measured as a percentage of total fatty acids, using capillary gas chromatography. Unconditional logistic regression modeling was used to obtain odds ratio estimates while adjusting for age, height, menopausal status and body mass index. We found inverse associations between breast cancer-risk and n-3 fatty acid levels in breast adipose tissue. Women in the highest tertile of alpha-linolenic acid (18:3 n-3) had an odds ratio of 0.39 (95% confidence intervals [CI] = 0.19-0.78) compared to women in the lowest tertile (trend p = 0.01). In a similar way, women in the highest tertile of docosahexaenoic acid (22:6 n-3) had an odds ratio of 0.31 (95% CI = 0.13-0.75) compared to women in the lowest tertile (trend p = 0.016). Women in the highest tertile of the long-chain n-3/total n-6 ratio had an odds ratio of 0.33 (95% confidence interval = 0.17-0.66) compared to women in the lowest tertile (trend p = 0.0002). In conclusion, our data based on fatty acids levels in breast adipose tissue suggest a protective effect of n-3 fatty acids on breast cancer risk and support the hypothesis that the balance between n-3 and n-6 fatty acids plays a role in breast cancer.     

Serum n-3 fatty acids, fish consumption and cancer mortality in six Japanese populations in Japan and Brazil.

Japanese people consume significant amounts of long chain n-3 polyunsaturated fatty acids (PUFAs) derived from fish, but the association of PUFAs with cancer mortality has not been fully investigated. To study geographic differences in n-3 PUFAs intake, we compared serum fatty acid and dietary fish intake among various Japanese populations having different rates of cancer mortality. The subjects were 50 men from each of five regions in Japan and 47 Japanese men from Sao Paulo, Brazil. All were randomly selected and aged 40 to 49 years. Serum fatty acids were measured by gas chromatography and the frequency of fish intake was obtained by a food frequency questionnaire. Significant geographic differences in serum fatty acid levels (% of total fatty acids) and fish intake (days/4 weeks) were observed. The percentages of serum total PUFA were similar in the six regions, though there was an almost three-fold difference in n-3 PUFAs content between Brazil (3.9%) and Akita (10.9%). The frequency of total fish intake corresponded to serum n-3 PUFAs composition. The relationship between cancer mortality and serum n-3 PUFAs levels was not clear, though an inverse association between prostate cancer and serum n-3 PUFAs levels appeared to exist. The results suggest that although serum n-3 PUFAs varied significantly, the observed geographic difference did not account for the different cancer risks at the population level.     

Dietary polyunsaturated fatty acids and breast cancer risk in Chinese women: a prospective cohort study

Breast cancer is the most common cancer in women. Controversy exists regarding the role of dietary fat in breast cancer etiology. We investigated the association of dietary polyunsaturated fatty acids (PUFAs) and the ratio of n-6 PUFAs to marine-derived n-3 PUFAs with breast cancer risk in the Shanghai Women's Health Study, a prospective cohort study including 72,571 cancer-free participants at baseline. Dietary fatty acid intake was determined using food frequency questionnaires. We used Cox proportional hazards analysis to estimate the relative risks (RRs) and 95% confidence intervals (CIs) for the association of breast cancer risk with dietary fatty acids consumption. In 583,998 person-years of follow-up, we identified 712 breast cancer cases. We found no association of breast cancer risk to dietary intake of linoleic acid, arachidonic acid, α-linolenic acid or marine-derived n-3 PUFA. We found a statistically significant interaction between n-6 PUFA intake, marine-derived n-3 PUFA intake and breast cancer risk (p = 0.008). Women with lower intake (the lowest tertile) of marine-derived n-3 PUFA and higher intake (the highest tertile) of n-6 PUFA had an increase risk for breast cancer (RR = 2.06; 95% CI = 1.27-3.34) compared to women with higher intake (the highest tertile) of marine-derived n-3 PUFAs and lower intake (the lowest tertile) of n-6 PUFAs after adjusting for potential confounders. The relative amounts of n-6 PUFA to marine-derived n-3 PUFAs may be more important for breast cancer risk than individual dietary amounts of these fatty acids.     

Dietary fat, cholesterol and colorectal cancer in a prospective study

The relationships between consumption of total fat, major dietary fatty acids, cholesterol, consumption of meat and eggs, and the incidence of colorectal cancers were studied in a cohort based on the Finnish Mobile Clinic Health Examination Survey. Baseline (1967-1972) information on habitual food consumption over the preceding year was collected from 9959 men and women free of diagnosed cancer. A total of 109 new colorectal cancer cases were ascertained late 1999. High cholesterol intake was associated with increased risk for colorectal cancers. The relative risk between the highest and lowest quartiles of dietary cholesterol was 3.26 (95% confidence interval 1.54-6.88) after adjusting for age, sex, body mass index, occupation, smoking, geographic region, energy intake and consumption of vegetables, fruits and cereals. Consumption of total fat and intake of saturated, monounsaturated, or polyunsaturated fatty acids were not significantly associated with colorectal cancer risk. Nonsignificant associations were found between consumption of meat and eggs and colorectal cancer risk. The results of the present study indicate that high cholesterol intake may increase colorectal cancer risk, but do not suggest the presence of significant effects of dietary fat intake on colorectal cancer incidence.     

Intake of Freshwater Fish and Associated Fatty Acids and Risk of Breast Cancer

To investigate the association between intake of freshwater fish and their fatty acids and the risk of breastcancer in Chinese women, we conducted a case-control study with 669 cases and 682 population-based controlsin Jiangsu Province of China. A structured questionnaire was used to elicit detailed information. Unconditionallogistic regression analysis was performed to calculate odds ratios (ORs) and 95% confidence intervals (CIs). Totalfreshwater fish intake was linked to decrease in the adjusted OR for breast cancer, but without dose-dependence.Analyses by freshwater fish species showed that consumption of black carp and silver carp was inversely relatedto breast cancer risk, with adjusted-ORs for the highest intake category of black carp (≥500g/month) of 0.54(95%CI=0.33-0.92; P trend<0.002) and for silver carp (≥1000g/month) of 0.19 (95%CI=0.11-0.33; P trend<0.001).In contrast, consumption of crucian carp was positively related to breast cancer risk, with an adjusted OR forthe highest intake category (≥1000g/month) of 6.09 (95%CI=3.04-12.2; P trend<0.001). Moderate intakes of SFA,PUFA, n3-PUFA and n6-PUFA from freshwater fish may decrease the risk of breast cancer among premenopausalwomen. The findings of this study suggest that intake of freshwater fish and their fatty acids may modify risk ofbreast cancer, and that different species of freshwater fish could have a different actions on breast cancer risk.Future epidemiologic studies are needed to know the effects of freshwater fish intake on breast cancer risk andthe cause of these effects.     

Opposing associations of serum n-3 and n-6 polyunsaturated fatty acids with colorectal adenoma risk: an endoscopy-based case-control study

Several human and animal studies have shown that n-3 polyunsaturated fatty acids (PUFA) might be associated with a decreased risk, whereas other studies showed that n-6 PUFA may be associated with an increased risk of colorectal cancer. However, results from these studies are not consistent. We evaluated the associations between serum n-3 and n-6 PUFA levels and colorectal adenoma risk in an endoscopy-based case-control study, conducted in The Netherlands between 1997 and 2002. We included 363 cases of colorectal adenomas and 498 adenoma-free controls. Serum fatty acids were measured in cholesteryl esters. Logistic regression models were used to calculate odds ratios (OR), which were adjusted for age, gender and alcohol intake. Total serum n-3 PUFA levels were inversely associated with colorectal adenoma risk, the OR comparing the third tertile with the first tertile was 0.67 [95% confidence interval (CI) 0.46-0.96, p for trend = 0.03]. Serum eicosapentaenoic acid (EPA; C20:5n-3) and docosahexaenoic acid (DHA; C22:6n-3) and the n-3/n-6 ratio were inversely associated with colorectal adenoma risk, but these were not statistically significant. In contrast, the risk of colorectal adenomas was increased by total n-6 PUFA with an OR of 1.68 (95% CI, 1.17-2.42, p for trend = 0.006) and by linoleic acid (LA; C18:2n-6) with an OR of 1.65 (95% CI, 1.15-2.38, p for trend = 0.007). This is the first observational study that simultaneously finds an inverse association of serum n-3 PUFA and a positive association of n-6 PUFA with colorectal adenoma risk.     

Breast cancer and the western diet: role of fatty acids and antioxidant vitamins

Epidemiological reports are inconsistent on the association between breast cancer risk and the dietary intake of either individual fatty acids or of antioxidant vitamins. It is postulated here that the inconsistencies are in part due to interactions between the two classes of nutrients at the level of the cell membrane, affecting their potential role in mammary carcinogenesis. In this review, the effects of specific dietary fatty acids and antioxidant vitamins on experimental mammary cancer systems are compared with reported epidemiological associations of the same agents with breast cancer risk in humans. An increased ratio of n-3 to n-6 polyunsaturated fatty acids (PUFAs) in the diet inhibits the growth of the rat mammary cancer model. There is also evidence that members of the n-3 PUFA series can inhibit the growth of human breast cancer cells both in vitro and in explants. Clinical trials of supplementary n-3 PUFAs in conjunction with a reduced fat intake have been proposed for breast cancer prevention. It is postulated that further dietary supplementation with vitamin E and a retinoid is likely to increase the effectiveness of such a diet. A study of this type allows better control of specific dietary components than prospective trials of dietary fat reduction which are presently under evaluation. In particular, it is suggested that studies focusing on a single nutrient often fail to recognise interactions with other nutrients.     

Prospective investigation of poultry and fish intake in relation to cancer risk

Dietary guidelines advise consumers to limit intake of red meat and choose lean protein sources, such as poultry and fish. Poultry consumption has been steadily increasing in the United States, but the effect on cancer risk remains unclear. In a large U.S. cohort, we prospectively investigated poultry and fish intake and cancer risk across a range of malignancies in men and women. Diet was assessed at baseline (1995-1996) with a food frequency questionnaire in 492,186 participants of the NIH-AARP Diet and Health Study. Over a mean follow-up of 9 years, we identified 74,418 incident cancer cases. In multivariable Cox proportional hazards regression models, we estimated the substitution and addition effects of white meat (poultry and fish) intake in relation to cancer risk. In substitution models with total meat intake held constant, a 10-g (per 1,000 kcal) increase in white meat intake offset by an equal decrease in red meat intake was associated with a statistically significant reduced (3%-20%) risk of cancers of the esophagus, liver, colon, rectum, anus, lung, and pleura. In addition models with red meat intake held constant, poultry intake remained inversely associated with esophageal squamous cell carcinoma, liver cancer, and lung cancer, but we observed mixed findings for fish intake. As the dietary recommendations intend, the inverse association observed between white meat intake and cancer risk may be largely due to the substitution of red meat. Simply increasing fish or poultry intake, without reducing red meat intake, may be less beneficial for cancer prevention.