Blood levels of long-chain polyunsaturated fatty acids, aspirin, and the risk of colorectal cancer.

BACKGROUND: N-3 fatty acids may decrease risk of colorectal cancer by inhibiting the cyclooxygenase-2 enzyme and production of proinflammatory eicosanoids derived from arachidonic acid (20:4n-6). Aspirin also inhibits the cyclooxygenase-2 enzyme and may share with n-3 fatty acids a potential mechanism to decrease the risk of colorectal cancer. METHODS: We conducted a nested case-control analysis using blood samples collected from the Physicians' Health Study participants in 1982 to 1984. N-3 and n-6 fatty acid levels were measured using gas-liquid chromatography for 178 men who developed colorectal cancer through December 31, 1995 and 282 age- and smoking-matched controls. We used conditional logistic regression to examine associations. All statistical tests were two-sided. RESULTS: Total long-chain n-3 fatty acids were nonsignificantly inversely associated with colorectal cancer risk [relative risk (RR) for highest versus lowest quartile, 0.60; 95% confidence interval (95% CI), 0.32 to 1.11; P(trend) = 0.10], after adjustment for possible confounders. We observed potential interaction between randomized aspirin assignment and long-chain n-3 fatty acid levels (P(interaction) = 0.04). Among men not on aspirin, RRs (95% CI) for increasing quartiles of long-chain n-3 fatty acids were 1.00 (reference), 0.60 (0.28-1.28), 0.51 (0.22-1.17), and 0.34 (0.15-0.82), P(trend) = 0.006. For participants taking aspirin, there was no additional benefit of increasing n-3 fatty acid levels. The RR (95% CI) for the highest versus lowest quartile of n-6 fatty acids was 0.64 (0.35-1.17). CONCLUSIONS: Blood levels of long-chain n-3 fatty acids were associated with decreased risk of colorectal cancer among men not using aspirin. N-6 fatty acids were nonsignificantly inversely associated with colorectal cancer risk.     

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.     

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.     

Dietary intakes of fat and fatty acids and risk of breast cancer: a prospective study in Japan

To examine the possible association of dietary fat and fatty acids with breast cancer risk in a population with a low total fat intake and a high consumption of fish, we analyzed data from the Japan Collaborative Cohort (JACC) Study. From 1988 to 1990, 26 291 women aged 40-79 years completed a questionnaire on dietary and other factors. Intakes of fat or fatty acids were estimated by using a food frequency questionnaire. Rate ratios (RR) were computed by fitting proportional hazards models. During the mean follow-up of 7.6 years, 129 breast cancer cases were documented. We found no clear association of total fat intake with breast cancer risk; the multivariate-adjusted RR across quartiles were 1.00, 1.29, 0.95, and 0.80 (95% confidence interval [CI] 0.46-1.38). A significant decrease in the risk was detected for the highest quartile of intake compared with the lowest for fish fat and long-chain n-3 fatty acids; the RR were 0.56 (95% CI 0.33-0.94) and 0.50 (0.30-0.85), respectively. A decreasing trend in risk was also suggested with an increasing intake of saturated fatty acids (trend P = 0.066). Among postmenopausal women at baseline, the highest quartile of vegetable fat intake was associated with a 2.08-fold increase in risk (95% CI 1.05-4.13). This prospective study did not support any increase in the risk of breast cancer associated with total or saturated fat intake, but it suggested the protective effects of the long-chain n-3 fatty acids that are abundant in fish.     

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.     

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.     

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.     

Possible beneficial effect of fish and fish n-3 polyunsaturated fatty acids in breast and colorectal cancer.

Breast and colorectal cancer are main causes of death in industrialized countries. In these cancers dietary factors appear to play beneficial or adverse roles. One of the possible beneficial factors may be fish intake or the n-3 polyunsaturated fatty acids from fish, as found in epidemiological and clinical studies. In population studies, high intake of fish during many years is associated with reduced risks of breast and colorectal cancer. Prospective and case-control studies either do not show an association between fish intake and cancer risks or show reduced risks at high fish intakes. In these studies, fish consumption may have been too low or may not reflect fish consumption over a longer period. In population, case-control, and prospective studies, fish and fish n-3 polyunsaturated fatty acids were not found to increase cancer risks. Clinical studies on markers of colorectal cancer indicate that fish n-3 polyunsaturated fatty acids may reduce cancer risk. In several studies in which the effect of fish consumption on cancer risk was investigated, meat and meat products were positively related to cancer risk, suggesting that cancer risks might be reduced more effectively when meat and meat products in meals are replaced by fish. In conclusion, the existing knowledge suggests that an increase in the consumption of fish and fish n-3 polyunsaturated fatty acids in industrialized countries may contribute to lower breast and colorectal cancer risks.     

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.     

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.     

A prospective study of fish, marine fatty acids, and bladder cancer risk among men and women (United States)

Objective To evaluate prospectively the association between intakes of fish, marine fatty acids, and bladder cancer risk in two ongoing cohorts, the Health Professionals Follow-up Study and the Nurses’ Health Study. Methods During 16 and 18 years of follow-up, 501 and 235 incident cases of bladder cancer were diagnosed among men and women, respectively. Cox proportional hazard models were used to estimate incidence rate ratios (RR) and 95% confidence intervals (CI) between fish intake and bladder cancer risk adjusting for age, total caloric intake, pack-years of cigarette smoking, and current smoking. Results We observed no significant overall association between total fish intake and bladder cancer risk, even when we compared ≥1 servings of fish per day to fish intake ≤1–3 servings per month. Among men, a statistically significant lower risk of bladder cancer was observed among men consuming fish or high marine fatty acid, after excluding the first 4 years of follow-up (MV RR = 0.60; 95% CI, 0.38–0.94, for ≥1 total fish servings per day compared to ≤1–3 servings per month). Conclusions Overall, these findings suggest that fish intake is not likely to be appreciably associated with the risk of bladder cancer.     

Dietary glycemic load, carbohydrate, sugar, and colorectal cancer risk in men and women.

Hyperinsulinemia may explain excess colorectal cancer among individuals who are overweight or inactive. Recent studies have observed elevated colorectal cancer risk among individuals with elevated insulin levels 2 hours after oral glucose challenge or with elevated plasma C-peptide levels. The effect of consuming a high glycemic diet on colorectal risk, however, remains uncertain. Two prospective cohort studies, the Nurses' Health Study and the Health Professionals Follow-up Study, contributed up to 20 years of follow-up. After exclusions, 1,809 incident colorectal cancers were available for analyses. Dietary glycemic load (GL) was calculated as a function of glycemic index (postprandial blood glucose response as compared with a reference food), carbohydrate content, and frequency of intake of individual foods reported on food frequency questionnaires. Multivariable Cox proportional hazards models were used to adjust for potential confounders. Intakes of dietary carbohydrate, GL, overall glycemic index, sucrose, and fructose were not associated with colorectal cancer risk in women. A small increase in risk was observed in men with high dietary GL (multivariate relative risk, 1.32; 95% confidence interval, 0.98-1.79; highest versus lowest quintile), sucrose or fructose (multivariate relative risk, 1.37; 95% confidence interval, 1.05-1.78; highest versus lowest quintile of fructose, P = 0.008). Associations were slightly stronger among men with elevated body mass index (> or =25 kg/m(2)). Results among women were similar after stratifying by body mass index or physical activity. High intakes of GL, fructose, and sucrose were related to an elevated colorectal cancer risk among men. For women, however, these factors did not seem to increase the risk of colorectal cancer.     

Dietary marine n-3 fatty acids in relation to risk of distal colorectal adenoma in women.

Epidemiologic studies of dietary marine n-3 fatty acids and risk of colorectal cancer have been inconsistent, and their relation to risk of colorectal adenoma has not been evaluated in detail. We examined dietary marine n-3 fatty acids and the ratio of marine n-3 to total n-6 fatty acids (n-3/n-6 ratio) in relation to risk of adenoma of the distal colon or rectum among 34,451 U.S. women who were initially free of colorectal cancer or polyps, who completed a semiquantitative food frequency questionnaire in 1980, and who underwent endoscopy from 1980 to 1998. We documented 1,719 distal colorectal adenoma cases (705 large adenomas, 897 small adenomas, 1,280 distal colon adenomas, and 505 rectal adenomas) during 18 years of follow-up. Neither dietary marine n-3 fatty acids nor n-3/n-6 ratio were associated with risk of total distal colorectal adenoma after adjustment for age and established risk factors [multivariable relative risk (RR) for extreme quintiles of dietary marine n-3 fatty acids = 1.04; 95% confidence interval (95% CI), 0.84-1.27, P(trend) = 0.66; RR for extreme quintiles of n-3/n-6 ratio = 1.02; 95% CI, 0.83-1.25; P(trend) = 0.86]. Similarly, no significant associations were observed separately for distal colon or rectal adenoma. However, higher intake of dietary marine n-3 fatty acids was nonsignificantly but suggestively inversely associated with large adenoma (RR, 0.74; 95% CI, 0.54-1.01; P(trend) = 0.16) but directly associated with small adenoma (RR, 1.36; 95% CI, 1.02-1.81; P(trend) = 0.09). Our findings do not support the hypothesis that a higher intake of marine n-3 fatty acids or a higher n-3/n-6 ratio reduces the risk of distal colorectal adenoma but are suggestive that higher intake may reduce the progression of small adenomas to large adenomas.     

Plasma phospholipids fatty acids,dietary fatty acids,and breast cancer risk

Purpose

This study prospectively investigates associations between fatty acids assessed in plasma phospholipids (PPL) and diet, and breast cancer risk, including subgroups defined by hormone receptor status.

Methods

We performed a case-cohort analysis within the Melbourne Collaborative Cohort Study using a random sample of 2,021 women and 470 breast cancer cases. At baseline, fatty acids were assessed in PPL and estimated from diet using a 121-item food frequency questionnaire. Hazard ratios (HR) and 95 % confidence intervals (CI) were estimated using Cox regression.

Results

Breast cancer risk was positively associated with %PPL saturated fatty acids (SFA); HR_Q5vsQ1 = 1.64 (95 % CI 1.17–2.30); p trend = 0.004. Positive associations were found for ER+ or PR+ tumors for %PPL SFA and palmitic acid and for ER?/PR? tumors for %PPL n-6 polyunsaturated fatty acid (PUFA), TFA, TFA 16:1, and TFA 18:1n-7 (all p homogeneity <0.05). Breast cancer risk was inversely associated with dietary docosapentaenoic acid (DPA); HR_Q5vsQ1 = 0.57 (95 % CI 0.40–0.82); p trend = 0.001 [with similar inverse associations observed for dietary docosahexaenoic (DHA) and eicosapentaenoic acid (EPA)] and positively associated with dietary n-6:n-3 PUFA. Inverse associations for ER?/PR? tumors were found for dietary dihomo-γ-linolenic acid (DGLA) for older women (p homogeneity = 0.04).

Conclusions

Breast cancer risk was positively associated with %PPL SFA and the ratio of dietary n-6 to n-3 PUFA and inversely associated with dietary long-chain n-3 PUFA intake. Some associations between fatty acids and breast cancer varied by age and tumor phenotype defined by hormone receptor status. Increased intake of fish and other foods rich in long-chain n-3 PUFAs and reduced n-6 PUFA intake might reduce breast cancer risk.

     

A prospective study of intake of fish and marine fatty acids and prostate cancer.

Experimental studies suggest that marine fatty acids have an antitumor effect on prostate tumor cells. The aim of this study was to investigate whether high consumption of fish and marine fatty acids reduces the risk of prostate cancer in humans. We followed 47882 men participating in the Health Professionals Follow-up Study. Dietary intake was assessed in 1986, 1990, and 1994, using a validated food frequency questionnaire. During 12 years of follow-up, 2482 cases of prostate cancer were diagnosed, of which 617 were diagnosed as advanced prostate cancer including 278 metastatic prostate cancers. Eating fish more than three times per week was associated with a reduced risk of prostate cancer, and the strongest association was for metastatic cancer (multivariate relative risk, 0.56; 95% confidence interval, 0.37-0.86, compared with infrequent consumption, i.e., less than twice per month). Intake of marine fatty acids from food showed a similar but weaker association. Each additional daily intake of 0.5 g of marine fatty acid from food was associated with a 24% decreased risk of metastatic cancer. We found that men with high consumption of fish had a lower risk of prostate cancer, especially for metastatic cancer. Marine fatty acids may account for part of the effect, but other factors in fish may also play a role.     

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.     

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 omega-3 and omega-6 fatty acids and risk of ovarian cancer

Objectives

Limited experimental evidence suggests that omega-3 polyunsaturated (n-3) fatty acids inhibit the proliferation of ovarian cancer cells in vitro, whereas omega-6 polyunsaturated (n-6) fatty acids have been shown to promote carcinogenesis, but epidemiological studies to date have been inconclusive. Our aim was to evaluate the role of polyunsaturated fatty acids in ovarian carcinogenesis.

Methods

Participants in the Australian Ovarian Cancer Study (1,366 cases and 1,414 population controls) self-completed risk factor and food frequency questionnaires. Logistic regression models were used to calculate adjusted odds ratio (OR) and 95?% confidence intervals (CI).

Results

We found no association between intake of total n-3 fatty acids from foods, or the individual n-3 fatty acids—alpha-linolenic, eicosapentaenoic, docosapentaenoic, docosahexaenoic acids—and ovarian cancer risk. High intake of total n-6 fatty acids was inversely associated with risk (OR for highest vs. lowest category 0.78, 95?% CI 0.60–1.00, p-trend 0.04); however, the association was restricted to n-6 fatty acids from avocado, vegetables, and nuts. Neither higher intake of the individual n-6 fatty acids nor the ratio of n-3 to n-6 fatty acids was associated with ovarian cancer risk. We found no evidence that risk varied by supplement use.

Conclusions

Our data provide no evidence of a protective role for n-3 fatty acids in ovarian carcinogenesis. The benefit, if any, of higher intake of n-6 fatty acids is due to general properties of the food sources, rather than due to the n-6 fatty acids per se.     

Total fluid intake and use of individual beverages and risk of renal cell cancer in two large cohorts.

Moderate alcohol consumption has been inversely associated with risk of renal cell cancer in recent prospective studies, and increased total fluid intake has been hypothesized to be a possible mechanism. We prospectively examined the associations between total fluid and beverage intakes and risk of renal cell cancer. Among 88,759 women followed for 20 years in the Nurses' Health Study, and 47,828 men followed for 14 years in the Health Professionals Follow-up Study, we documented 248 incident cases of renal cell cancer. We assessed consumption of beverages every 2 to 4 years using a validated semiquantitative food frequency questionnaire, and total fluid intake was derived from the frequency of consumption of 18 to 22 beverage items. Cox proportional hazards regression was used to estimate study-specific multivariate relative risks (RR), which were pooled using a random-effects model. We found no association between total fluid intake and risk of renal cell cancer; the pooled multivariate RR for the highest quartile versus the lowest was 0.99 (95% confidence interval, 0.63-1.55; P, test for trend = 0.78). Alcohol intake was marginally inversely associated with renal cell cancer risk; compared with nondrinkers, the pooled multivariate RR for > or = 15 g/d was 0.66 (95% confidence interval, 0.43-1.00; P, test for trend = 0.07). We did not find clear associations between intakes of coffee, tea, milk, juice, soda, punch, and water and risk of renal cell cancer. Our data suggest an inverse association between alcohol intake and risk of renal cell cancer, but do not support the hypothesis that greater total fluid intake reduces the risk of renal cell cancer.     

Fatty-acid composition in serum phospholipids and risk of breast cancer: an incident case-control study in Sweden.

The study of the relationship between dietary intake of fatty acids and the risk of breast cancer has not yielded definite conclusions with respect to causality, possibly because of methodological issues inherent to nutritional epidemiology. To evaluate the hypothesis of possible protection of n-3 polyunsaturated fatty acids (PUFA) against breast cancer in women, we examined the fatty-acid composition of phospholipids in pre-diagnostic sera of 196 women who developed breast cancer, and of 388 controls matched for age at recruitment and duration of follow-up, in a prospective cohort study in Umea, northern Sweden. Individual fatty acids were measured as a percentage of total fatty acids, using capillary gas chromatography. Conditional logistic-regression models showed no significant association between n-3 PUFA and breast-cancer risk. In contrast, women in the highest quartile of stearic acid had a relative risk of 0.49 (95% confidence interval, 0.22-1.08) compared with women in the lowest quartile (trend p = 0.047), suggesting a protective role of stearic acid in breast-cancer risk. Besides stearic acid, women in the highest quartile of the 18:0/18:1 n-9c ratio had a relative risk of 0.50 (95% confidence interval, 0.23-1.10) compared with women in the lowest quartile (trend p = 0.064), suggesting a decrease in breast-cancer risk in women with low activity of the enzyme delta 9-desaturase (stearoyl CoA desaturase), which may reflect an underlying metabolic profile characterized by insulin resistance and chronic hyper-insulinemia.