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.     

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.     

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.     

Association of Dietary Intake Ratio of n-3/n-6 Polyunsaturated Fatty Acids with Breast Cancer Risk in Western and Asian Countries: A Meta-Analysis

Objective: This systematic review and meta-analysis were performed to determine association of dietary intake ratioof n-3/n-6 polyunsaturated fatty acids with breast cancer risk in Western and Asian countries. Methods: The authorsconducted a meta-analysis of published research articles on association of dietary intake ratio of n-3/n-6 polyunsaturatedfatty acids (PUFAs) with breast cancer risk in Western and Asian countries published between January 2000 and February2019 in online article databases of PubMed, ProQuest and EBSCO. Pooled risk ratios (RR) were calculated usingfixed and random-effect models. Publication bias was visually evaluated by performing funnel plots and statisticallyassessed by Egger’s and Begg’s tests. Data were processed by using Stata version 14.2 (Stata Corporation). Results:This study reviewed 913 articles. There were 13 studies included in systematic review continued by meta-analysisof relevant data with total number of samples: 275,264 patients. The results showed dietary intake ratio of n-3/n-6PUFAs with breast cancer risk in Western and Asian countries (RR = 0.99; 95% CI: 0.92-1.07). Dietary intake ratioof n-3/n-6 PUFAs with breast cancer risk in Western countries reached (RR = 0.98; 95% CI: 0.91-1.06) and there wasany significant publication bias for studies included. Dietary intake ratio of n-3/n-6 PUFAs with breast cancer risk inAsian countries reached (RR = 1.18; 95% CI: 0.94-1.47) and there was not any significant publication bias for studiesincluded. Conclusion: This analysis confirmed association of dietary intake ratio of n-3/n-6 PUFAs with breast cancerrisk in Western and Asian countries. Higher dietary intake ratio is associated with lower risk of breast cancer in Asiancountries rather than Western countries. This study suggests increasing dietary intake ratio n-3/n-6 PUFAs will providebenefit for breast cancer prevention.     

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.     

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.     

Serum fatty acids and risk of breast cancer in a nested case-control study of the New York University Women's Health Study.

Migrant and experimental animal studies suggest that differences in breast cancer incidence rates may be related, in part, to intake of dietary fat. The experimental evidence indicates that total fat, saturated, and n-6 polyunsaturated fatty acids (PUFAs) may stimulate both mammary tumor growth and metastasis, whereas n-3 PUFAs may have a tumor-inhibiting effect. Overall, epidemiological studies do not appear to confirm such observations. Within a cohort of women in the New York University Women's Health Study, the fatty acid composition of serum phospholipids was analyzed by gas chromatography among 197 pre- and postmenopausal clinically identified breast cancer subjects and their matched controls. Individual fatty acids in serum phospholipids were expressed as a percentage of total fatty acids. No significant difference was observed in the proportion of saturated fatty acids (SFAs), monounsaturated fatty acids, or n-6 and n-3 PUFAs between cases and controls. After menopause, total SFAs were positively associated with the risk of breast cancer [odds ratio (OR) = 1.96, 95% confidence interval (CI): 0.73-5.25; P = 0.05] after adjustment for potential confounding factors. Myristc acid (C14:0) was suggestive of a small increase in breast cancer risk in premenopausal women (OR = 2.22, 95% CI: 0.78-6.31), whereas palmitic acid (C16:0) showed similar trends in postmenopausal women (OR = 2.57, 95% CI: 0.99-6.61). Overall, total PUFAs (n-6 and n-3) were suggestive of a small protective effect (OR = 0.59, 95% CI: 0.31-1.09). No significant associations were found between other fatty acids and the risk of breast cancer. The study suggested evidence of an association between serum levels of SFAs and the risk of breast cancer in postmenopausal women. Neither individual n-3 fatty acids of marine origin, eicosapentaenoic acid (C20:5 n-3), and docosahexaenoic acid (C22:6 n-3), nor n-6 PUFAs were related to cancer risk in this study.     

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.     

Dietary fat, fat subtypes, and breast cancer risk: lack of an association among postmenopausal women with no history of benign breast disease.

A recent study among 13,707 postmenopausal women without benign breast disease (BBD) from the Breast Cancer Detection Demonstration Project (BCDDP) cohort found breast cancer risk associated with greater total fat, unsaturated fat, and oleic acid intake. We assessed the associations between cumulative averaged dietary intake from 1980, 1984, 1986, and 1990 with breast cancer risk through 1994 among 44,697 postmenopausal participants without BBD in the Nurses' Health Study (NHS). Multivariate Cox proportional hazard models, with age as the time variable, provided the estimated rate ratios (RRs) with 95% confidence intervals (CIs) from the 14 years of follow-up and the 1,071 breast cancer cases. In the Nurses' Health Study, breast cancer rates over the time period from 1980 to 1994 did not increase significantly with greater total fat [quintile (Q) 5 versus Q1 RR, 0.94; 95% CI, 0.77-1.15], saturated fat (RR(Q5 to Q1), 0.88; 95% CI, 0.70-1.12), unsaturated fat (RR(Q5 to Q1), 1.16; 95% CI, 0.92-1.46), oleic acid (RR(Q5 to Q1), 1.13; 95% CI, 0.81-1.57), linoleic acid (RR(Q5 to Q1), 0.93; 95% CI, 0.74-1.16), trans fatty acid (RR(Q5 to Q1), 0.9184; 95% CI, 0.73-1.13), or energy intake (RR(Q5 to Q1), 0.81; 95% CI, 0.67-0.99). A parallel analysis restricted to the same time period as the BCDDP study did not differ substantially. We found no increase in the rate of breast cancer with greater intake of dietary fat and fat subtypes among postmenopausal women without a history of BBD.     

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.     

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.     

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.

     

Low alpha-linolenic acid content of adipose breast tissue is associated with an increased risk of breast cancer

Data derived from experimental studies suggest that alpha-linolenic acid may have a protective effect in breast cancer. Observations obtained from epidemiological studies have not allowed conclusions to be drawn about a potential protective effect of dietary alpha-linolenic acid on breast cancer, possibly because of methodological issues. This case-control study conducted in an homogeneous population from a central area in France was designed to explore the hypothesis that alpha-linolenic acid inhibits breast cancer, using fatty acid levels in adipose breast tissue as a biomarker of past qualitative dietary intake of fatty acids. Biopsies of adipose breast tissue at the time of diagnosis were obtained from 123 women with invasive non-metastatic breast carcinoma. 59 women with benign breast disease served as controls. Individual fatty acids were analysed by capillary gas chromatography. An unconditional logistic regression model was used to obtain odds ratio estimates whilst adjusting for age, menopausal status and body mass index (BMI). No association was found between fatty acids (saturates, monounsaturates, long-chain polyunsaturates n-6 or n-3) and the disease, except for alpha-linolenic acid which showed an inverse association with the risk of breast cancer. The relative risk of breast cancer for women in the highest quartile of adipose breast tissue alpha-linolenic acid level was 0.36 (95% confidence interval=0.12-1.02) compared with those in the lowest quartile (P trend=0.026), suggesting a protective effect of alpha-linolenic acid in the risk of breast cancer. The effects of dietary alpha-linolenic on the risk of breast cancer warrant further study.     

Dietary total fat and fatty acids intake,serum fatty acids and risk of breast cancer: A meta‐analysis of prospective cohort studies

Results from prospective cohort studies on the association between dietary total fat and fatty acids intake and risk of breast cancer remain controversial. Pertinent prospective cohort studies were identified by a search of Embase and PubMed from inception to September 2015. Study‐specific relative risks (RRs) with 95% confidence intervals were pooled using a random‐effect model. Between‐study heterogeneity and publication bias were assessed, and sensitivity analysis was conducted. Twenty‐four independent studies on dietary total fat and fatty acids intake and seven studies on serum fatty acids were included. The pooled RR of breast cancer for the highest vs. lowest category of dietary total fat intake was 1.10 (1.02–1.19); however, no association was observed in studies adjusting for traditional risk factors of breast cancer. No association was observed between animal fat, vegetable fat, saturated fatty acids (SFA), monounsaturated fatty acids (MUFA), polyunsaturated fatty acids (PUFA), n‐3 PUFA, n‐6 PUFA, eicosapentaenoic acid, docosahexaenoic acid, alpha‐linolenic acid, oleic acid, linoleic acid and arachidonic acid and risk of breast cancer. The pooled RRs of breast cancer for the highest vs. lowest category of serum SFA, MUFA, PUFA, n‐3 PUFA and n‐6 PUFA were 1.00 (0.78–1.28), 1.41 (0.99–2.03), 0.59 (0.27–1.30), 0.81 (0.60–1.10) and 0.84 (0.60–1.18), respectively. Results from this meta‐analysis suggested that dietary total fat and fatty acids might be not associated with risk of breast cancer.     

A prospective study of polyunsaturated fatty acid levels in blood and prostate cancer risk.

BACKGROUND: Animal models suggest that n-3 fatty acids inhibit prostate cancer proliferation, whereas n-6 fatty acids promote it, but epidemiologic studies do not uniformly support these findings. METHODS: A nested case-control study was conducted among 14,916 apparently healthy men who provided blood samples in 1982. Blood fatty acid levels were determined for 476 men diagnosed with prostate cancer during a 13-year follow-up and their matched controls. Conditional logistic regression was used to estimate the relative risks (RR) and 95% confidence intervals (95% CI) of total, non-aggressive (stage A/B and Gleason < 7) and aggressive (stage C/D, Gleason >or= 7, subsequent distant metastasis or death) prostate cancer associated with blood levels of specific fatty acids expressed as percentages of total fatty acids. RESULTS: Whole blood levels of all long-chain n-3 fatty acids examined and of linoleic acid were inversely related to overall prostate cancer risk (RR(Q5vs.Q1), 0.59; 95% CI, 0.38-0.93; P(trend) = 0.01 for total long-chain n-3 fatty acids and RR(Q5vs.Q1), 0.62; 95% CI, 0.41-0.95; P(trend) = 0.03 for linoleic). Blood levels of gamma-linolenic and dihomo-gamma-linolenic acids, fatty acids resulting from the metabolism of linoleic acid, were directly associated with prostate cancer (RR, 1.41; 95% CI, 0.94-2.12; P(trend) = 0.05 for gamma-linolenic and RR, 1.54; 95% CI, 1.03-2.30; P(trend) = 0.02 for dihomo-gamma-linolenic acid). Levels of arachidonic and alpha-linolenic acids were unrelated to prostate cancer. CONCLUSIONS: Higher blood levels of long-chain n-3 fatty acids, mainly found in marine foods, and of linoleic acid, mainly found in non-hydrogenated vegetable oils, are associated with a reduced risk of prostate cancer. The direct associations of linoleic acid metabolites with prostate cancer risk deserve further investigation.     

Fat consumption and breast cancer: preliminary results from the E3N-Epic cohort]

Recent reviews have concluded that a high consumption of total, saturated or animal, fat could possibly increase the risk of breast cancer. However these results are highly dependent on the type of study; indeed, most of the prospective studies do not support this association. In this paper, we investigated the relationship between fat consumption and breast cancer risk in the E3N-Epic cohort, the French component of the European Prospective Investigation into Cancer and Nutrition. Assessment of fat consumption was based on daily intakes of food items and nutrients using a food-frequency questionnaire. Relative risk (RR) estimates were calculated using Cox's proportional hazards model. After an average of 3.4 years of follow-up, 838 cases of incident breast cancer were recorded in a study population of 65,879 women. The mean caloric intake was 2,073 kcal (SD 540), with 37% of calories coming from fat intake. Milk products and vegetable oils were the main sources of fat in the diet. We found a small positive association between fat intake and breast cancer risk. Compared with the lowest, women in the highest quartile of fat intake had a 37% higher risk of breast cancer (RR 1.37, CI95% = 0.99-1.89). There was no detectable association between fatty acids or food items contributing to fat intake and breast cancer risk. These analyses suggest there is a need for longer follow-up time to increase statistical power and confirm these tendencies.     

A case-control study of diet and the risk of ovarian cancer.

Epidemiologic studies have suggested that some dietary factors may play a role in the etiology of ovarian cancer, but the findings have been inconsistent. We assessed the association of ovarian cancer with dietary factors in a population-based case-control study in Canada. Diet information was collected on 442 incident cases of ovarian cancer diagnosed in 1994 to 1997 and 2,135 population controls via a self-administered questionnaire. Compared with women in the lowest quartile of cholesterol intake, those in the second, third, and fourth quartiles had a multivariate adjusted odds ratio [OR; 95% confidence interval (95% CI)] of 1.12 (0.81-1.56), 1.20 (0.85-1.68), and 1.42 (1.03-1.97), respectively (P for trend = 0.031). Higher egg consumption was also associated with a nonsignificant increase in ovarian cancer risk. The ORs (95% CIs) for ovarian cancer were 0.77 (0.60-1.04) and 0.76 (0.56-0.99) among women in the highest quartile of total vegetable and cruciferous vegetable intake as compared with women in the lowest quartile. Women who took supplements of vitamin E, beta-carotene, and B-complex vitamins for > or =10 years had ORs (95% CIs) of 0.49 (0.30-0.81), 0.31 (0.11-0.91), and 0.61 (0.36-1.05), respectively. However, we did not observe an association of ovarian cancer risk with dietary fat intake, including saturated, monounsaturated, and polyunsaturated fatty acids, protein, carbohydrate, dietary fiber, fruit, dairy products, meat products, fish, chicken, grain products, nut products, baked desserts, margarine, butter, mayonnaise, and supplement of multiple vitamins, vitamin A, vitamin C, calcium, iron, zinc, and selenium. Our findings suggested that ovarian cancer risk was positively associated with higher consumption of dietary cholesterol and eggs and inversely associated with higher intake of total vegetables and cruciferous vegetables and supplementation of vitamin E, beta-carotene, and B-complex vitamins.     

Dietary fat and breast cancer in postmenopausal women according to ethnicity and hormone receptor status: the Multiethnic Cohort Study

Dietary fat has been widely studied as a risk factor for breast cancer, with little consistency in results. The Multiethnic Cohort Study (MEC) provides an opportunity to assess this relationship for possible heterogeneity across different racial/ethnic groups, as well as by stratification on several other variables associated with risk. Therefore, we investigated the associations between dietary fat, overall and by type, and breast cancer risk among 85,089 postmenopausal women who entered the MEC by completing a comprehensive dietary questionnaire in 1993 to 1996. During a mean follow-up of 12 years, 3,885 incident invasive breast cancer cases were identified. The multivariate HR [95% confidence interval (CI)] for the highest versus lowest quintile of intake was 0.94 (95% CI, 0.85-1.05) for total fat and 0.93 (95% CI, 0.83-1.04) for saturated fat. Other specific types of dietary fat, including individual fatty acids, were not related to risk of postmenopausal breast cancer. We found no heterogeneity in these null findings across the five ethnic groups. Furthermore, we found no evidence that the association between dietary fat and postmenopausal breast cancer risk differed by estrogen/progesterone receptor status, tumor stage, body mass index, hormone replacement therapy use, follow-up period, family history of breast cancer, and smoking status at baseline. In conclusion, this comprehensive prospective analysis in the MEC does not support a role of adult intake of dietary fat in the etiology of postmenopausal breast cancer.