Skip to main content
NCBI home page
NIHPA Author Manuscripts logoLink to NIHPA Author Manuscripts
. Author manuscript; available in PMC: 2014 Aug 12.
Published in final edited form as: Cancer Epidemiol Biomarkers Prev. 2013 Apr;22(4):697–707. doi: 10.1158/1055-9965.EPI-12-1196-T

Dietary Fat, Fatty Acids and Risk of Prostate Cancer in the NIH-AARP Diet and Health Study

Colleen Pelser 1, Alison M Mondul 2, Albert R Hollenbeck 3, Yikyung Park 2
PMCID: PMC4129658  NIHMSID: NIHMS440835  PMID: 23549401

Abstract

Background

Observational studies report inconsistent associations of fat and fatty acids with prostate cancer.

Methods

We investigated associations between dietary fats and fatty acids and risk of prostate cancer in the National Institutes of Health (NIH)-AARP Diet and Health Study. Diet was assessed at baseline with self-administered food-frequency questionnaires. Cases were determined by linkage with state cancer registries. Hazard ratios (HR) and 95% confidence intervals (CIs) were estimated with Cox proportional hazards models.

Results

Among 288,268 men with average follow-up of 9 years, 23,281 prostate cancer cases (18,934 non-advanced and 2,930 advanced including 725 fatal cases) were identified. Total fat, and mono- and polyunsaturated fat INTAKES were not associated with incidence of prostate cancer. Saturated fat intake was related to increased risk of advanced prostate cancer (HRQuintile 5 vs. Qunitile 1 (Q1 vs. Q5)1.21; 95% CI 1.00–1.46; p-for-trend=0.03) and fatal prostate cancer (HR Q5 vs. Q1 1.47; 95% CI 1.01–2.15; p-for-trend=0.04). Alpha-linolenic acid (ALA) intake was related to increased risk of advanced prostate cancer (HRQ5 vs. Q1 1.17; 95 % CI:1.04–1.31; p-for-trend 0.01). Eicosapentanoic acid (EPA) intake was related to decreased risk of fatal prostate cancer (HR Q5 vs. Q1 0.82; 95% CI 0.64–1.04; p-for-trend 0.02).

Conclusion

Our study suggests that the associations of fat and fatty acids differ by prostate cancer severity. Saturated fat, ALA and EPA intakes were related to the risk of advanced or fatal prostate cancer, but not to non-advanced prostate cancer.

Impact

identifying factors associated with advanced prostate cancer could reduce morbidity and mortality.

Keywords: Dietary Fat, Fatty Acids, Alpha-linolenic acid (ALA), Eicosapentanoic acid (EPA), Prostate Cancer

Introduction

Prostate cancer incidence varies internationally, with the highest rates in western industrialized countries [1]. For example, incidence in the United States is 83.8 per 100,000 men, compared to 22.7 in Japan, and 22.4 in the Republic of Korea [2]. Furthermore, migration studies demonstrate that prostate cancer incidence is higher among Japanese immigrants to the United States than in their Japan, suggesting that diet or lifestyle factors may contribute to carcinogenesis [3, 4].

One of the characteristics of Western diets is a high intake of fat, and dietary fat and several fatty acids, such n-3 and n-6 polyunsaturated fatty acids (PUFAs), have been postulated to play a role in prostate cancer etiology and progression. Fatty acids and their metabolites are involved in numerous pathways with potential impact on carcinogenesis. For example, n-6 fatty acids serve as precursors to eicosanoids, which in turn are converted to prostaglandins and other inflammatory molecules. Metabolic pathways of n-3 fatty acids are less well known, but among nude mice fed diets high in the n-3 long-chain fatty acids eicosapentanoic acid (EPA) and docosahexanoic acid (DHA), reduced growth of prostate cancer xenografts was observed [5]. EPA and DHA also inhibited in vitro proliferation of prostate cancer cell lines, whereas the n-6 fatty acids linoleic acid (LA) and arachidonic acid (AA) stimulated proliferation [6, 7]. More recently, EPA and DHA were shown to inhibit conversion to androgen-independence in an in vitro model of prostate cancer progression [8], and this effect was correlated with inhibition of pathways involved with expression of fatty acid synthase, a protein upregulated in prostate cancer development [9].

Epidemiologic studies of total dietary fat intake and prostate cancer risk are inconsistent and do not support a strong positive association [10, 11]. A summary estimate of 7 prospective cohort studies showed no association between total fat and types of fat intakes and risk of prostate cancer [12]. Studies of specific fatty acids have been similarly inconsistent; no congruent pattern of increased or decreased risk of prostate cancer with higher intakes of n-6 or n-3 fatty acids, respectively, has emerged from the literature. Most analyses show no association of individual PUFAs with prostate cancer [13–15], while a few have reported an increased risk of prostate cancer with higher intakes of alpha-linolenic acid (ALA), an n-3 fatty acid, [11, 16–18].

However, some studies suggested that the association differed by prostate cancer severity: intake of saturated fat has been associated with advanced prostate cancer in some [19–22], but not all studies [11, 23]. In addition, one study of serum fatty acid concentrations found that higher circulating levels of n-3 fatty acids were related to an increased risk of high-grade, but not low-grade, prostate cancer [24]. Another found that a higher ratio of n-6/n-3 fatty acids intake was related to an increased risk for high grade prostate cancer [25].

Previous observational studies had relatively small number of cases with a narrow range of fat intake and many lacked statistical power to detect modest associations between fat intake and risk of advanced or fatal prostate cancer. Therefore, we examined associations between total dietary fat, types of fat, and individual fatty acids with incidence of overall as well as advanced and fatal prostate cancer in a very large prospective cohort with a wide range of fat intake.

Materials and Methods

Study Population

Details of the NIH-AARP Diet and Health Study have been previously described [26]. Briefly, the study consists of over 500,000 men and women aged 50–71 years who resided in one of six states (California, Florida, Pennsylvania, New Jersey, North Carolina, and Louisiana) or in one of two metropolitan areas (Atlanta, Georgia and Detroit, Michigan). Participants completed a mailed questionnaire at baseline between 1995 and 1996, and an additional risk factor questionnaire was subsequently mailed in 1996–1997 to people who did not have self-reported prevalent cancer at baseline. The study was approved by the Special Studies Institutional Review Board of the National Cancer Institute and informed consent was obtained from all participants at baseline. Among the 339,667 men who completed the baseline questionnaire, we excluded those whose questionnaires were completed by proxy (n=14,495); who reported a history of cancer (except non-melanoma skin cancer) at baseline (n=28,641); who had end-stage renal disease at baseline (n=485); who had self-reported poor health at baseline (n=4,958); or who reported extreme intakes of total energy (n=2,503) or total fat (n=317). Our final analytic cohort consisted of 288,268 men.

Cancer Ascertainment

Incident prostate cancer was ascertained through December 31, 2006 by probabilistic linkage to eight state cancer registries and three additional state cancer registries (Arizona, Nevada, and Texas) where participants tended to move to during follow-up. These cancer registries have been certified by the North American Association of Central Cancer Registries to capture at least 90% of cancer incidences within two years of cancer incidence. Cancer registry data included cancer diagnosed, diagnosis date, morphology code, grade, and stage information. Participants were also followed by annual matching of the cohort database with the National Change of Address database maintained by the U.S. Postal Service and through processing of undeliverable mail, other address update services and direct responses from participants. Vital status was ascertained through December 31, 2008 by linkage with the Social Security Administration death master file and the National Death Index Plus.

Total prostate cancer cases included all men diagnosed with first primary prostate cancer of any grade. Non-advanced prostate cancer cases were defined as men whose tumors that had not penetrated the prostate capsule, and did not have lymph node involvement or metastases (stage T0-T2, and N0 and M0 of the American Joint Commission on Cancer 1997 TNM classification system). Advanced prostate cancer were those with tumors that penetrated the prostate capsule (stage T3-T4), or had lymph node involvement (N1) or metastasis (M1), or who died of prostate cancer during follow-up. Fatal cases were participants with a first primary diagnosis of prostate cancer and who died of prostate cancer during follow-up.

Assessment of diet and other risk factors

At baseline diet was assessed using a self-administered food frequency questionnaire (FFQ) which asked participants to report their usual intake of 124 food items during the previous year. We assessed frequency of food and beverage consumption for the previous 12 months using 10 pre-defined categories of intake ranging from “never” to “6+ times per day” for beverages, and “never” to “2+ times per day” for solid foods. Portion sizes and nutrient intakes were estimated from the 1994–1996 US Department of Agriculture’s Continuing Survey of Food Intakes by Individuals. In order to more accurately quantify fat intake, the FFQ also included 21 questions about consumption of foods that were low fat and those that contained added fats or creamers used in food preparation. This FFQ was validated by comparing intake estimates to that of two non-consecutive 24-hour food recalls among a subset of 2,053 participants. Correlation coefficients between instruments for total fat intake (adjusted for energy intake) were 0.72 for men and 0.62 for women [27]. The validity of FFQs to measure polyunsaturated and fatty acid intake has been reported for the all-male participants of the Health Professionals Follow-up Study (HPFS)[28]. The Spearman correlation coefficients between an FFQ and a subcutaneous fat aspirate for total polyunsaturated fatty acids and eicosapentanoic acid (EPA) were 0.50 and 0.47, respectively.

The baseline questionnaire also collected information about non-diet risk factors, including demographic characteristics, height, body weight, medical history, family history of cancer, smoking status, and vigorous physical activity. A subsequent risk factor questionnaire administered in 1996–1997 asked for more detailed medical history including Prostate-Specific Antigen (PSA) screening. In this risk-factor questionnaire, men were asked whether they had had a PSA screening test within the past 3 years.

Statistical Analyses

Hazard ratios (HR) and 95% confidence intervals (CI) for associations with prostate cancer were estimated using Cox proportional hazards models, with person-years as the time variable. Person-years of follow-up were calculated from the date the baseline questionnaire was returned until the date of cancer diagnosis, death from any cause, move out of the cancer registry area, or end of follow-up, whichever was first. For analysis of fatal prostate cancer, cases were followed from study entry until death, therefore person-years were calculated from baseline to prostate cancer death, death from other causes, or end of follow-up, whichever was first. Variables were considered as potential confounding variables and included in models if they were known or hypothesized to be associated with either fatty acid intake or risk of prostate cancer, based on results from previous studies or exploration of these data. Age, race/ethnicity (Non-Hispanic White, Non-Hispanic Black, Hispanic, Asian, Pacific Islander, or American Indian/Alaskan Native), and family history of prostate cancer (having a first degree relative with prostate cancer) were included due to well-known associations with prostate cancer incidence. Marital status (married or not), education (high school or less, some college, or college graduate), self-reported diabetes (yes or no), and PSA screening within 3 years prior to the baseline assessment (yes, no, or unknown) were included. Models were also adjusted for total energy, alcohol intake, intake of tomatoes, body mass index (BMI) in three levels (<25,25 to <30, and 30 kg/m2 and above), the frequency of engaging in 20 minutes or more vigorous physical activity (never or rarely, 1–3 times per month, 1–2 times per week, 3–4 times per week, or 5+ times per week) and a smoking variable which combined information of current smoking status and average dose during periods of smoking (never smoker, former smoker of ≤20 cigarettes per day, former smoker of >20 cigarettes per day, current smoker of ≤20 cigarettes per day, and current smoker of >20 cigarettes per day). For participants with missing data on covariates, an indicator variable was included in the models. In addition to full models, parsimonious models were created for advanced and fatal prostate cancers. Covariates were included in these models if they changed the estimate of effect for saturated fat by ≥10%. Because results from these parsimonious models and results from the fully adjusted models did not differ, and to allow for comparison to previous studies that adjusted for similar covariates, only the fully-adjusted results are presented. The proportional hazards assumption was evaluated by modeling interaction terms of time and each exposure of interest.

Fat and fatty acid intakes were expressed as percentages of total energy, tomatoes were expressed servings per 1,000 calories, and all models included adjustment for total calories. Percentage of calories from trans fat was calculated by summing percentage of calories from trans-hexadecenoic acid (16:1), trans-octadecenoic acid (18:1), and trans-octadecadienoic acid (18:2). Percentage of calories from total n-3 PUFAs was calculated similarly to a prior study in this cohort [29] by summing percent calories of ALA (18:3), parinaric acid (PNA; 18:4), EPA (20:5), docosapentanoic acid (DPA; 22:5) and DHA (22:6). In addition, because ALA is metabolically different from other long chain n-3 fatty acids and tends to come from different food sources, we created an additional variable summing percentage of calories from EPA and DHA, which have been shown to be metabolically active [5–8], and, at least for EPA, have been demonstrated to be measured with some validity by FFQ [28]. Percentage of calories from total n-6 PUFAs was calculated by summing LA (18:2) and AA (20:4). The ratio of n-6 to n-3 PUFAs was calculating by dividing the total percentage of calories from n-6 by the total percentage of calories from total n-3 fatty acids.

Intakes of fat and fatty acids were categorized into quintiles and entered into models as nominal variables with the lowest category as the reference group. Tests for trend of categorical variables were conducted by assigning each participant the median value of their quintile of intake and modeling these values as a continuous variable. For analyses of saturated, mono- and polyunsaturated fat, all models were mutually adjusted for each type of fat.

Results

During an average of 9 years of follow-up, a total of 23,281 incident prostate cancer cases were ascertained. Of these, 18,934 were non-advanced cases, 1,417 had lack of information on stage and grade, and 2,930 were advanced cases (including 725 fatal prostate cancer cases).

Median dietary fat intake was 20% of calories from fat for the lowest quintile of intake, and 40% calories from fat for the highest quintile. Compared to men in the lowest quintile of total fat intake, men in the highest quintile tended to be white, have less education, have higher BMI at baseline, and be less likely to engage in physical activity or to have had a PSA test in the last 3 years. They also were more likely to have self-reported history of any type of diabetes and to be a current smoker, but were less likely to drink 15 or more grams of alcohol per day (Table 1).

Table 1.

Baseline characteristics by quintile of % of energy from total fat among 288,268 men in the NIH-AARP Diet and Health Study

Quintile I Quintile II Quintile III Quintile IV Quintile V
Median total fat intake, % of energy 20.3 26.5 30.6 34.6 39.9
Race/ethnicity %†
 Non-Hispanic White 90.8 92.3 92.9 93.3 93.7
 Non-Hispanic Black 2.8 2.7 2.6 2.6 2.6
 Hispanic 2.5 2.1 1.9 1.7 1.3
 Other 2.7 1.9 1.5 1.3 1.1
Education, %†
 ≤11 years 4.8 5.0 5.5 6.1 6.9
 12 years or completed high school 13.2 14.0 15.4 16.9 18.1
 post-high school or some college 28.5 30.2 31.4 32.4 34.2
 college and post graduate 50.9 48.2 45.3 42.0 37.9
Married, % 82.7 85.7 86.3 86.5 84.5
Family history of prostate cancer, % 8.0 8.2 8.5 8.5 8.4
PSA test in last 3 years*, % 75.1 74.2 71.9 69.1 65.2
Self-reported diabetes, % 6.5 8.2 9.2 10.5 14.0
Tomato (pyramid servings/1000 kcal)
 0 to 0.25 73.3 73.2 74.5 76.7 80.1
 More than 0.25 26.7 26.8 25.5 23.3 19.9
Alcohol
 <15 grams/day 58.6 67.2 72.4 77.9 84.7
 15 or more grams/day 41.4 32.8 27.6 22.1 15.3
Smoking history, %†
 Never smoked 30.6 30.6 30.6 29.0 26.2
 Former smoker 58.5 58.1 56.7 55.4 53.3
 Current smoker 6.8 7.5 9.0 11.7 16.4
Median BMI at baseline 25.9 26.5 26.6 27.1 27.4
Physical activity 5 or more times/week, % 29.1 23.0 20.3 18.2 16.8
Open in a new tab
*

Among 178,331 men who answered the risk factor questionnaire

†

Proportions may not total to 100% due to missing or incomplete information.

Main food sources for saturated fatty acids included margarine & butter, beef, and milk and other dairy. Main food sources for monounsaturated fatty acids included margarine & butter, oils, mayonnaise & salad dressings, and beef. Among the n-3 PUFAs, ALA came mainly from oils, mayonnaise & salad dressings, margarine & butter, and desserts & baked goods (e.g. cakes, pies, brownies, etc.), whereas the other n-3 PUFAs (EPA, DHA, DPA, and PNA) came from intake of fish, poultry, and eggs. The n-6 PUFA AA was largely supplied by poultry, beef, and eggs in the diet, while LA came from oils, mayonnaise & salad dressings, margarine & butter, and nuts & seeds.

Intakes of total fat, poly-unsaturated fat, and total trans fatty acids were not associated with incidence of total, non-advanced, advanced or fatal prostate cancer (Table 2). Saturated fat intake was related to an increased risk of advanced prostate cancer (highest vs. lowest quintile HR 1.21; 95% CI 1.00–1.46; p-for trend=0.03), and to fatal prostate cancer (HR 1.47; 95% CI 1.01–2.15; p-for-trend=0.04). There was a suggestive trend for decreased risk of advanced prostate cancer with increasing intake of monounsaturated fat (HR 0.80; 95% CI 0.64–1.01), although it was not statistically significant (p-for-trend=0.08). These associations were not attenuated when adjusting for total meat or red meat intake.

Table 2.

Risk of prostate cancer with increasing quintiles of total dietary fat, and saturated, monounsaturated, polyunsaturated, and trans fat.

Quintiles of Intake
I II III IV V p-for-trend
Total dietary fat
 Quintile median(% energy) 20.3 26.5 30.6 34.6 40.0
 Nonadvanced cases (n) 4013 3912 3792 3754 3463
  Multivariable HR 1.00 1.00 1.00 1.03 1.01 0.43
  95% CI (0.96–1.05) (0.95–1.04) (0.98–1.07) (0.96–1.06)
 Advanced cases (n) 571 593 583 613 570
  Multivariable HR 1.00 1.04 1.03 1.11 1.07 0.16
  95% CI (0.93–1.17) (0.92–1.16) (0.98–1.24) (0.95–1.21)
 Fatal cases (n) 128 128 154 164 151
  Multivariable HR 1.00 0.98 1.15 1.19 1.09 0.24
  95% CI (0.77–1.25) (0.91–1.46) (0.94–1.52) (0.85–1.40)
Saturated fat
 Quintile median(% energy) 5.8 7.8 9.4 10.9 13.3
 Nonadvanced cases (n) 4031 3968 3757 3730 3448
  Multivariable HR 1.00 1.01 0.99 1.02 1.01 0.76
  95% CI (0.96–1.07) (0.93–1.05) (0.95–1.09) (0.94–1.08)
 Advanced cases (n) 582 567 595 616 570
  Multivariable HR 1.00 1.05 1.14 1.22 1.21 0.03
  95% CI (0.91–1.20) (0.97–1.33) (1.03–1.45) (1.00–1.46)
 Fatal cases (n) 125 118 162 160 160
  Multivariable HR 1.00 1.07 1.50 1.47 1.47 0.04
  95% CI (0.79–1.44) (1.08–2.08) (1.04–2.10) (1.01–2.15)
Monounsaturated fat
 Quintile median(% energy) 7.4 9.9 11.6 13.3 15.5
 Nonadvanced cases (n) 3963 3931 3819 3748 3473
  Multivariable HR 1.00 1.02 1.01 1.04 1.04 0.46
  95% CI (0.96–1.08) (0.95–1.09) (0.96–1.13) (0.94–1.13)
 Advanced cases (n) 601 554 614 593 568
  Multivariable HR 1.00 0.88 0.91 0.85 0.80 0.08
  95% CI (0.76–1.02) (0.76–1.09) (0.69–1.04) (0.64–1.01)
 Fatal cases (n) 137 132 139 161 156
  Multivariable HR 1.00 0.90 0.83 0.88 0.78 0.31
  95% CI (0.66–1.22) (0.57–1.20) (0.58–1.33) (0.49–1.24)
Polyunsaturated fat
 Quintile median(% energy) 4.4 5.7 6.7 7.7 9.5
 Nonadvanced cases (n) 3822 3854 3848 3734 3676
  Multivariable HR 1.00 1.01 1.01 0.99 0.99 0.54
  95% CI (0.96–1.06) (0.96–1.06) (0.93–1.04) (0.93–1.05)
 Advanced cases (n) 595 554 565 601 615
  Multivariable HR 1.00 0.94 0.96 1.03 1.09 0.09
  95% CI (0.82–1.06) (0.84–1.10) (0.89–1.19) (0.93–1.28)
 Fatal cases (n) 160 132 123 143 167
  Multivariable HR 1.00 0.80 0.72 0.82 0.96 0.65
  95% CI (0.62–1.03) (0.55–0.96) (0.61–1.10) (0.70–1.31)
Total trans fatty acids
 Quintile median(% energy) 1.1 1.6 2.0 2.4 3.2
 Nonadvanced cases (n) 3918 3798 3750 3770 3698
  Multivariable HR 1.00 0.99 1.00 1.03 1.00 0.53
  95% CI (0.95–1.04) (0.96–1.05) (0.98–1.08) (0.96–1.05)
 Advanced cases (n) 582 606 552 632 558
  Multivariable HR 1.00 1.04 0.95 1.10 0.97 0.79
  95% CI (0.92–1.16) (0.85–1.07) (0.98–1.23) (0.85–1.09)
 Fatal cases (n) 143 139 137 147 159
  Multivariable HR 1.00 0.92 0.90 0.92 0.95 0.80
  95% CI (0.73–1.17) (0.71–1.14) (0.73–1.17) (0.75–1.21)
Open in a new tab
*

All HR include adjustment for age at entry, race, family history of prostate cancer, education, marital status, PSA testing in the past 3 years, physical activity, smoking, self-reported diabetes, BMI at baseline, calories, alcohol and intake of tomatoes.

There were no associations between total n-3 or n-6 PUFAs and risk of overall or any subset of prostate cancer, nor was there any association with the ratio of n-6/n-3 fatty acids (Table 3). EPA+DHA, there were decreased HRs for fatal prostate cancer in the top three quintiles of intake, but neither the estimates nor the trend were statistically significant. ALA intake was related to an increased risk of advanced prostate cancer (highest vs. lowest quintile HR 1.17; 95 % CI 1.04–1.31; p-for-trend 0.01), but not fatal prostate cancer. There was a suggestive trend of decreased risk of fatal prostate cancer with increasing intake of EPA (highest vs. lowest quintile HR 0.82; 95% CI 0.64–1.04; p-for-trend 0.02).

Table 3.

Risk of prostate cancer with increasing quintiles of n-6 and n-3 PUFAs, ratio of n-6 to n-3 PUFAs, essential fatty acids, and marine PUFAs

Quintiles of Intake
I II III IV V p-for-trend
Total n-6 fatty acids
 Quintile median (% energy) 3.8 5.0 5.9 6.9 8.6
 Nonadvanced cases (n) 3796 3897 3837 3758 3646
  Multivariable HR 1.00 1.04 1.03 1.02 1.01 0.92
  95% CI (0.99–1.09) (0.98–1.08) (0.97–1.07) (0.97–1.06)
 Advanced cases (n) 596 562 568 601 603
  Multivariable HR 1.00 0.93 0.94 1.00 1.02 0.42
  95% CI (0.83–1.05) (0.84–1.06) (0.89–1.12) (0.91–1.14)
 Fatal cases (n) 162 131 128 142 162
  Multivariable HR 1.00 0.80 0.76 0.83 0.95 0.98
  95% CI (0.63–1.01) (0.60–0.97) (0.60–0.97) (0.76–1.19)
Total n-3 fatty acids
 Quintile median (% energy) 0.45 0.57 0.66 0.77 0.95
 Nonadvanced cases (n) 3685 3810 3883 3833 3723
  Multivariable HR 1.00 1.04 1.06 1.06 1.04 0.14
  95% CI (0.99–1.09) (1.02–1.11) (1.01–1.11) (0.99–1.09)
 Advanced cases (n) 586 554 575 583 632
  Multivariable HR 1.00 0.93 0.96 0.98 1.06 0.13
  95% CI (0.83–1.05) (0.86–1.08) (0.87–1.10) (0.95–1.20)
 Fatal cases (n) 151 148 129 138 159
  Multivariable HR 1.00 0.97 0.82 0.87 1.00 1.00
  95% CI (0.76–1.20) (0.65–1.05) (0.67–1.11) (0.79–1.26)
Ratio n-6/n-3
 Quintile median 6.9 8.0 8.8 9.7 11
 Nonadvanced cases (n) 3796 3897 3837 3758 3646
  Multivariable HR 1.00 1.02 1.03 1.03 0.98 0.44
  95% CI (0.98–1.07) (0.98–1.07) (0.98–1.08) (0.94–1.03)
 Advanced cases (n) 588 597 619 565 561
  Multivariable HR 1.00 1.01 1.06 0.97 0.98 0.51
  95% CI (0.90–1.14) (0.95–1.19) (0.87–1.09) (0.87–1.10)
 Fatal cases (n) 147 143 149 147 139
  Multivariable HR 1.00 0.97 1.01 1.00 0.93 0.62
  95% CI (0.77–1.22) (0.80–1.27) (0.79–1.26) (0.74–1.18)
LA (linoleic acid)
 Quintile median (% energy) 3.8 5.0 5.9 6.9 8.5
 Nonadvanced cases (n) 3791 3901 3834 3762 3646
  Multivariable HR 1.00 1.04 1.03 1.02 1.01 0.94
  95% CI (0.99–1.09) (0.98–1.08) (0.98–1.07) (0.97–1.06)
 Advanced cases (n) 596 565 563 603 603
  Multivariable HR 1.00 0.94 0.93 1.00 1.02 0.44
  95% CI (0.83–1.05) (0.83–1.05) (0.89–1.12) (0.90–1.14)
 Fatal cases (n) 162 133 125 140 165
  Multivariable HR 1.00 0.81 0.74 0.82 0.96 0.95
  95% CI (0.64–1.02) (0.59–0.94) (0.65–1.04) (0.77–1.21)
ALA (alpha-linolenic acid)
 Quintile median (% energy) 0.41 0.52 0.60 0.70 0.88
 Nonadvanced cases (n) 3746 3810 3875 3752 3751
  Multivariable HR 1.00 1.04 1.06 1.03 1.05 0.11
  95% CI (0.99–1.08) (1.02–1.11) (0.98–1.08) (1.00–1.10)
 Advanced cases (n) 550 586 563 592 639
  Multivariable HR 1.00 1.06 1.02 1.07 1.17 0.01
  95% CI (0.94–1.19) (0.90–1.15) (0.95–1.20) (1.04–1.31)
 Fatal cases (n) 136 152 129 144 164
  Multivariable HR 1.00 1.09 0.91 1.00 1.13 0.39
  95% CI (0.86–1.38) (0.71–1.16) (0.78–1.27) (0.89–1.43)
EPA (eicosapentanoic acid)
 Quintile median (% energy) 0.003 0.007 0.012 0.018 0.036
 Nonadvanced cases (n) 3487 3865 3831 3842 3909
  Multivariable HR 1.00 1.09 1.07 1.07 1.05 0.69
  95% CI (1.04–1.14) (1.02–1.12) (1.02–1.12) (1.00–1.10)
 Advanced cases (n) 568 583 596 627 556
  Multivariable HR 1.00 1.01 1.02 1.06 0.93 0.15
  95% CI (0.90–1.13) (0.91–1.15) (0.95–1.19) (0.82–1.04)
 Fatal cases (n) 165 175 138 121 126
  Multivariable HR 1.00 1.08 0.87 0.76 0.82 0.02
  95% CI (0.87–1.34) (0.69–1.09) (0.60–0.97) (0.64–1.04)
DPA (docosapentanoic acid)
 Quintile median (% energy) 0 0.0040 0.0058 0.0084 0.014
 Nonadvanced cases (n) 3593 3789 3871 3900 3781
  Multivariable HR 1.00 1.06 1.05 1.06 1.02 0.55
  95% CI (1.01–1.11) (1.00–1.10) (1.01–1.11) (0.98–1.07)
 Advanced cases (n) 569 609 610 560 582
  Multivariable HR 1.00 1.07 1.04 0.95 0.99 0.43
  95% CI (0.95–1.20) (0.93–1.17) (0.85–1.07) (0.88–1.11)
 Fatal cases (n) 176 160 136 115 138
  Multivariable HR 1.00 0.94 0.82 0.71 0.88 0.12
  95% CI (0.75–1.18) (0.65–1.02) (0.56–0.90) (0.70–1.11)
DHA (docosahexanoic acid)
 Quintile median (% energy) 0.0010 0.0019 0.0028 0.0040 0.0068
 Nonadvanced cases (n) 3611 3820 3825 3852 3826
  Multivariable HR 1.00 1.05 1.05 1.05 1.02 0.82
  95% CI (1.00–1.10) (1.00–1.10) (1.00–1.10) (0.98–1.07)
 Advanced cases (n) 531 617 613 604 565
  Multivariable HR 1.00 1.14 1.13 1.11 1.03 0.56
  95% CI (1.02–1.29) (1.01–1.27) (0.99–1.25) (0.91–1.16)
 Fatal cases (n) 154 175 132 133 131
  Multivariable HR 1.00 1.16 0.89 0.91 0.92 0.19
  95% CI (0.93–1.44) (0.70–1.12) (0.72–1.15) (0.73–1.17)
EPA + DHA
 Quintile median (% energy) 0.013 0.026 0.039 0.058 0.103
 Nonadvanced cases (n) 3557 3865 3778 3847 3887
  Multivariable HR 1.00 1.07 1.05 1.06 1.04 0.45
  95% CI (1.03–1.12) (1.00–1.10) (1.01–1.11) (1.00–1.10)
 Advanced cases (n) 557 582 628 601 562
  Multivariable HR 1.00 1.03 1.10 1.05 0.97 0.31
  95% CI (0.91–1.15) (0.98–1.23) (0.93–1.18) (0.86–1.09)
 Fatal cases (n) 161 166 140 130 128
  Multivariable HR 1.00 1.05 0.91 0.86 0.87 0.10
  95% CI (0.85–1.31) (0.72–1.14) (0.68–1.09) (0.68–1.10)
Open in a new tab
*

All HR include adjustment for age at entry, race, family history of prostate cancer, education, marital status, PSA testingin the past 3 years, physical activity, smoking, self-reported diabetes, BMI at baseline, calories, alcohol and intake of tomatoes.

We also explored the association of other individual fatty acids with risk of prostate cancer. There were no associations between any of these of individual fatty acids with non-advanced prostate cancer (Supplementary Table 1). There was a statistically significant trend of decreased risk between eruic acid (22:1) and risk of fatal prostate cancer (highest vs. lowest quintile HR 0.75; 95% CI 0.59–0.96; p-for trend=0.02), and increased risk of fatal prostate cancer with higher intake of trans-hexadecenoic acid (16:1; highest vs. lowest quintile HR 1.32; 95% CI 1.03–1.68; p-trend=0.04).

There were no significant interactions between PSA screening and the results for saturated fat, ALA or EPA.

Discussion

In this study we found that higher dietary intakes of saturated fat and ALA were associated with increased risk of advanced prostate cancer. Our findings on saturated fat are consistent with results reported for another large cohort study, the Health Professionals Follow-up Study [19]. Several case-control studies also showed a positive relationship of dietary saturated fat with risk of advanced prostate cancer [20–22, 30], or total prostate cancer [30, 31]. In contrast, in one other cohort study [15], and a few small case-control studies [32, 33] the authors found no association of saturated fat intake with advanced prostate cancer. In our previous study red meat intake (a main source of dietary saturated fat in this population) was positively associated with risk of advanced prostate cancer [34]. However, the results for saturated fat and advanced prostate cancer did not change appreciably with adjustment for red meat intake or with total meat intake, so the association is unlikely due to confounding with meat.

Our findings regarding an association of ALA with advanced prostate cancer are also consistent with results of the Health Professionals Follow-up Study [18, 19, 35], and with one other case control study [17]. In contrast, among studies that specifically examined aggressive prostate cancer (either advanced stage, high grade, or both), two prospective studies [13, 14], and three case-control studies failed to find an association [25, 36, 37].

There are various differences between the studies that could account for the different findings, such as varying sample sizes, dietary instruments and databases, ranges of fat intake, adjustment for potential confounders, and variation between study populations in factors such as PSA screening and stage distribution. On substantial difference between our study and other studies of ALA and advanced prostate cancer is sample size. Most studies examining the association of ALA had relatively small numbers of advanced cases (ranging from 36 to 858), whereas in our study we had 2,935 advanced prostate cancer cases available for analysis. In addition, with exception of the Netherlands Cohort Study, which had a similar range of ALA intake [13], the range in median intake between the lowest and the highest quintile (from 0.87 to 2.0 g/day) was higher in our study than most of the other studies (average of about 1.0 g/day to 1.5 g/day).

Differences in PSA screening practices could also affect studies of advanced prostate cancer, especially if the exposure is associated with rate of progression. Among frequently-screened populations, associations could be masked because the stage distribution would be skewed toward earlier stages, resulting in fewer advanced cases and less power to detect modest associations. This could be one explanation why a null association was found among the screening arm of the PLCO, as these men were screened yearly [14]. However, the lack of association among participants of the Netherlands Cohort Study, which was conducted in Europe where PSA screening was not widely adopted [13], remains to be explained.

A few of the earlier studies using fatty acid content of blood, serum, or plasma as biomarkers of fat intake found a positive association of ALA with prostate cancer risk [38–40], however these studies were small, with the number of cases ranging from 67 to 120, and they were not able to specifically examine associations with advanced or high grade disease. Later, three out of four studies that examined the relation of circulating ALA concentrations to the risk of advanced or high grade cancers found no association. Comparing the highest category to the lowest category of ALA concentration in relation to high grade (Gleason ≥ 7) prostate cancer, the Physician’s Health Study (PHS) [41] trial found a RR of 1.49 (95% CI, 0.67–3.27; p-for-trend=0.29), the Multiethnic Cohort Study (MEC) [42] found an OR of 0.60 (95% CI 0.17–2.14; p-for-trend=0.39), and the Prostate Cancer Prevention Trial (PCPT) [24] found an OR of 0.64 (95% CI 0.38–1.11; p-for-trend=0.17). Recently, the European Prospective Investigation into Cancer (EPIC) study [12] found a suggestive increased risk of high grade prostate (RR comparing the highest to the lowest, 1.79; 95% CI, 0.91–3.53; p-for-trend=0.014). Overall, studies of ALA concentration in blood do not support a hypothesis of increased risk of prostate cancer with higher ALA level.

In our study, we also found suggestive inverse association between EPA and fatal prostate cancer, a long-chain fatty acid derived mainly from fish. This observation is consistent with animal and in vitro data demonstrating protective effect of marine n-3 fatty acids on prostate cancer development and progression [5–8]. It is also consistent with some prospective epidemiologic studies that investigated the association of either total fish, or marine n-3 PUFAs with advanced prostate cancer or with prostate cancer mortality [35, 43, 44], but not with others [15, 22, 45]. Furthermore, in another analysis among this cohort, the fish component sub-score of the Alternate Mediterranean Diet Score, and the n-3 fatty acid component sub-score of the Alternate Healthy Eating Index were associated with an inverse association of fatal prostate cancer [47]. On the other hand, in our study we found no association of prostate cancer with intake of DHA, an important marine fatty acid that has been shown to have anti-proliferative effects in vitro [5–9], nor with the combination of EPA and DHA. Overall, our study only weakly supports a possible inverse association of marine fatty acids or fish intake with advanced or fatal prostate cancer.

Several studies have examined associations of EPA and DHA in blood with advanced or high grade prostate cancer (12, 24, 41–42) and reported inconsistent results. Three studies found no association between EPA in blood and risk of advanced or high grade prostate cancer [24, 42, 46], whereas the EPIC study [12] found that EPA concentration in plasma was related to an increased risk of high grade prostate cancer (RR 2.00; 95% CI 1.07–3.76; p-for-trend 0.031). DHA in blood was not related to the risk of advanced or high grade prostate cancer in the PHS, the MEC, or in the EPIC studies [42, 46], but was associated with a significantly increased risk of high grade prostate cancer (OR 2.50; 95% CI 1.34–4.65; p-for-trend 0.04) in the PCPT [24]. Relationships of the marine fatty acids to advanced, high grade, and fatal prostate cancer remain to be elucidated.

A major strength of this study was the large sample size, which allowed investigation of fats and fatty acids with advanced and fatal prostate cancer. In addition, dietary data were measured prospectively, which reduced error from recall bias, and this population had a relatively wide intake of dietary fat. On the other hand, measurement error is an inherent limitation in self-reported dietary assessment. Additionally, in this study we assessed diet only once, at baseline. Therefore, we could not examine the effects of early life exposure (e.g. childhood and young adulthood), or prolonged cumulative exposure to fat and fatty acids on the risk of prostate cancer. In addition, considering the long latency period of cancer, the duration of follow-up in our study may have been insufficient to detect an association. Furthermore, among our investigations of fats and fatty acids with prostate cancer outcomes, many different exposures were evaluated, increasing the likelihood that chance findings could arise among the multiple comparisons. Among the association that we did find, none were strikingly strong. Therefore we feel these findings should be interpreted cautiously and in light of the other relevant literature.

In summary, our large prospective cohort study found that the associations of fat and fatty acids differed by prostate cancer severity. Fat and fatty acid intakes were not related to the risk of non-advanced prostate cancer, whereas intakes of saturated fat, ALA, and EPA were related to the risk of advanced or fatal prostate cancer. More studies are needed to elucidate the role of fat and fatty acids in prostate cancer etiology.

Supplementary Material

1

Acknowledgments

This research was supported (in part) by the Intramural Research Program of the NIH, National Cancer Institute. Cancer incidence data from the Atlanta metropolitan area were collected by the Georgia Center for Cancer Statistics, Department of Epidemiology, Rollins School of Public Health, Emory University. Cancer incidence data from California were collected by the California Department of Health Services, Cancer Surveillance Section. Cancer incidence data from the Detroit metropolitan area were collected by the Michigan Cancer Surveillance Program, Community Health Administration, State of Michigan. The Florida cancer incidence data used in this report were collected by the Florida Cancer Data System (FCDC) under contract with the Florida Department of Health (FDOH). The views expressed herein are solely those of the authors and do not necessarily reflect those of the FCDC or FDOH. Cancer incidence data from Louisiana were collected by the Louisiana Tumor Registry, Louisiana State University Medical Center in New Orleans. Cancer incidence data from New Jersey were collected by the New Jersey State Cancer Registry, Cancer Epidemiology Services, New Jersey State Department of Health and Senior Services. Cancer incidence data from North Carolina were collected by the North Carolina Central Cancer Registry. Cancer incidence data from Pennsylvania were supplied by the Division of Health Statistics and Research, Pennsylvania Department of Health, Harrisburg, Pennsylvania. The Pennsylvania Department of Health specifically disclaims responsibility for any analyses, interpretations or conclusions. Cancer incidence data from Arizona were collected by the Arizona Cancer Registry, Division of Public Health Services, Arizona Department of Health Services. Cancer incidence data from Texas were collected by the Texas Cancer Registry, Cancer Epidemiology and Surveillance Branch, Texas Department of State Health Services. Cancer incidence data from Nevada were collected by the Nevada Central Cancer Registry, Center for Health Data and Research, Bureau of Health Planning and Statistics, State Health Division, State of Nevada Department of Health and Human Services.

We are indebted to the participants in the NIH-AARP Diet and Health Study for their outstanding cooperation. We also thank Sigurd Hermansen and Kerry Grace Morrissey from Westat for study outcomes ascertainment and management and Leslie Carroll at Information Management Services for data support and analysis.

Footnotes

The authors declare no conflicts of interest.

References

  • 1.Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA Cancer J Clin. 2005;55:74–108. doi: 10.3322/canjclin.55.2.74. [DOI] [PubMed] [Google Scholar]
  • 2.Ferlay JSH, Bray F, Forman D, Mathers C, Parkin DM. Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 10. [Accessed July 5, 2012];GLOBOCAN 2008 v1.2. 2010 http://globocan.iarc.fr.
  • 3.Shimizu H, Ross RK, Bernstein L, Yatani R, Henderson BE, Mack TM. Cancers of the prostate and breast among Japanese and white immigrants in Los Angeles County. Br J Cancer. 1991;63:963–966. doi: 10.1038/bjc.1991.210. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 4.Yu H, Harris RE, Gao YT, Gao R, Wynder EL. Comparative epidemiology of cancers of the colon, rectum, prostate and breast in Shanghai, China versus the United States. Int J Epidemio. 1991;20:76–81. doi: 10.1093/ije/20.1.76. [DOI] [PubMed] [Google Scholar]
  • 5.Connolly JM, Coleman M, Rose DP. Effects of dietary fatty acids on DU145 human prostate cancer cell growth in athymic nude mice. Nutr Cancer. 1997;29:114–119. doi: 10.1080/01635589709514611. [DOI] [PubMed] [Google Scholar]
  • 6.Rose DP. Effects of dietary fatty acids on breast and prostate cancers: evidence from in vitro experiments and animal studies. Am J Clin Nutr. 1997;66:1513S–1522S. doi: 10.1093/ajcn/66.6.1513S. [DOI] [PubMed] [Google Scholar]
  • 7.Hughes-Fulford M, Chen Y, Tjandrawinata RR. Fatty acid regulates gene expression and growth of human prostate cancer PC-3 cells. Carcinogenesis. 2001;22:701–707. doi: 10.1093/carcin/22.5.701. [DOI] [PubMed] [Google Scholar]
  • 8.Friedrichs W, Ruparel SB, Marciniak RA, deGraffenried L. Omega-3 fatty acid inhibition of prostate cancer progression to hormone independence is associated with suppression of mTOR signaling and androgen receptor expression. Nutr Cancer. 2011;63:771–777. doi: 10.1080/01635581.2011.570892. [DOI] [PubMed] [Google Scholar]
  • 9.Swinnen JV, Roskams T, Joniau S, Van Poppel H, Oyen R, Baert L, et al. Overexpression of fatty acid synthase is an early and common event in the development of prostate cancer. Int J Cancer. 2002;98:19–22. doi: 10.1002/ijc.10127. [DOI] [PubMed] [Google Scholar]
  • 10.American Institute for Cancer Research/World Cancer Research Fund. Food, nutrition, physical activity and the prevention of cancer: a global perspective. Washington, DC: AICR; 2007. [DOI] [PubMed] [Google Scholar]
  • 11.Dennis LK, Snetselaar LG, Smith BJ, Stewart RE, Robbins ME. Problems with the assessment of dietary fat in prostate cancer studies. Am J Epidemiol. 2004;160:436–444. doi: 10.1093/aje/kwh243. [DOI] [PubMed] [Google Scholar]
  • 12.Crowe FL, Allen NE, Appleby PN, Overvad K, Aardestrup IV, Johnsen NF, et al. Fatty acid composition of plasma phospholipids and risk of prostate cancer in a case-control analysis nested within the European Prospective Investigation into Cancer and Nutrition. Am J Clin Nutr. 2008;88:1353–1363. doi: 10.3945/ajcn.2008.26369. [DOI] [PubMed] [Google Scholar]
  • 13.Schuurman AG, van den Brandt PA, Dorant E, Brants HA, Goldbohm RA. Association of energy and fat intake with prostate carcinoma risk: results from The Netherlands Cohort Study. Cancer. 1999;86:1019–1027. [PubMed] [Google Scholar]
  • 14.Koralek DO, Peters U, Andriole G, Reding D, Kirsh V, Subar A, et al. A prospective study of dietary alpha-linolenic acid and the risk of prostate cancer (United States) Cancer Causes Control. 2006;17:783–791. doi: 10.1007/s10552-006-0014-x. [DOI] [PubMed] [Google Scholar]
  • 15.Park SY, Murphy SP, Wilkens LR, Henderson BE, Kolonel LN. Fat and meat intake and prostate cancer risk: the multiethnic cohort study. Int J Cancer. 2007;121:1339–1345. doi: 10.1002/ijc.22805. [DOI] [PubMed] [Google Scholar]
  • 16.Ramon JM, Bou R, Romea S, Alkiza ME, Jacas M, Ribes J, et al. Dietary fat intake and prostate cancer risk: a case-control study in Spain. Cancer Causes Control. 2000;11:679–685. doi: 10.1023/a:1008924116552. [DOI] [PubMed] [Google Scholar]
  • 17.De Stefani E, Deneo-Pellegrini H, Boffetta P, Ronco A, Mendilaharsu M. Alpha-linolenic acid and risk of prostate cancer: a case-control study in Uruguay. Cancer Epidemiol Biomarkers Prev. 2000;9:335–338. [PubMed] [Google Scholar]
  • 18.Giovannucci E, Liu Y, Platz EA, Stampfer MJ, Willett WC. Risk factors for prostate cancer incidence and progression in the health professionals follow-up study. Int J Cancer. 2007;121:1571–1578. doi: 10.1002/ijc.22788. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 19.Giovannucci E, Rimm EB, Colditz GA, Stampfer MJ, Ascherio A, Chute CC, et al. A prospective study of dietary fat and risk of prostate cancer. J Natl Cancer Inst. 1993;85:1571–1579. doi: 10.1093/jnci/85.19.1571. [DOI] [PubMed] [Google Scholar]
  • 20.West DW, Slattery ML, Robison LM, French TK, Mahoney AW. Adult dietary intake and prostate cancer risk in Utah: a case-control study with special emphasis on aggressive tumors. Cancer Causes Control. 1991;2:85–94. doi: 10.1007/BF00053126. [DOI] [PubMed] [Google Scholar]
  • 21.Whittemore AS, Kolonel LN, Wu AH, John EM, Gallagher RP, Howe GR, et al. Prostate cancer in relation to diet, physical activity, and body size in blacks, whites, and Asians in the United States and Canada. J Natl Cancer Inst. 1995;87:652–661. doi: 10.1093/jnci/87.9.652. [DOI] [PubMed] [Google Scholar]
  • 22.Kristal AR, Cohen JH, Qu P, Stanford JL. Associations of energy, fat, calcium, and vitamin D with prostate cancer risk. Cancer Epidemiol Biomarkers Prev. 2002;11:719–725. [PubMed] [Google Scholar]
  • 23.Carayol M, Grosclaude P, Delpierre C. Prospective studies of dietary alpha-linolenic acid intake and prostate cancer risk: a meta-analysis. Cancer Causes Control. 2010;21:347–355. doi: 10.1007/s10552-009-9465-1. [DOI] [PubMed] [Google Scholar]
  • 24.Brasky TM, Till C, White E, Neuhouser ML, Song X, Goodman P, et al. Serum phospholipid fatty acids and prostate cancer risk: results from the prostate cancer prevention trial. Am J Epidemiol. 2011;173:1429–1439. doi: 10.1093/aje/kwr027. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 25.Williams CD, Whitley BM, Hoyo C, Grant DJ, Iraggi JD, Newman KA, et al. A high ratio of dietary n-6/n-3 polyunsaturated fatty acids is associated with increased risk of prostate cancer. Nutr Res. 2011;31:1–8. doi: 10.1016/j.nutres.2011.01.002. [DOI] [PubMed] [Google Scholar]
  • 26.Schatzkin A, Subar AF, Thompson FE, Harlan LC, Tangrea J, Hollenbeck AR, et al. Design and serendipity in establishing a large cohort with wide dietary intake distributions : the National Institutes of Health-American Association of Retired Persons Diet and Health Study. Am J Epidemiol. 2001;154:1119–1125. doi: 10.1093/aje/154.12.1119. [DOI] [PubMed] [Google Scholar]
  • 27.Thompson FE, Kipnis V, Midthune D, Freedman LS, Carroll RJ, Subar AF, et al. Performance of a food-frequency questionnaire in the US NIH-AARP (National Institutes of Health-American Association of Retired Persons) Diet and Health Study. Public Health Nutr. 2008;11:183–195. doi: 10.1017/S1368980007000419. [DOI] [PubMed] [Google Scholar]
  • 28.Hunter DJ, Rimm EB, Sacks FM, Stampfer MJ, Colditz GA, Litin LB, et al. Comparison of measures of fatty acid intake by subcutaneous fat aspirate, food frequency questionnaire, and diet records in a free-living population of US men. Am J Epidemiol. 1992;135:418–427. doi: 10.1093/oxfordjournals.aje.a116302. [DOI] [PubMed] [Google Scholar]
  • 29.Thiebaut AC, Kipnis V, Chang SC, Subar AF, Thompson FE, Rosenberg PS, et al. Dietary fat and postmenopausal invasive breast cancer in the National Institutes of Health-AARP Diet and Health Study cohort. J Natl Cancer Inst. 2007;99:451–462. doi: 10.1093/jnci/djk094. [DOI] [PubMed] [Google Scholar]
  • 30.Slattery ML, Schumacher MC, West DW, Robison LM, French TK. Food-consumption trends between adolescent and adult years and subsequent risk of prostate cancer. Am J Clin Nutr. 1990;52:752–757. doi: 10.1093/ajcn/52.4.752. [DOI] [PubMed] [Google Scholar]
  • 31.Lee MM, Wang RT, Hsing AW, Gu FL, Wang T, Spitz M. Case-control study of diet and prostate cancer in China. Cancer Causes Control. 1998;9:545–552. doi: 10.1023/a:1008840105531. [DOI] [PubMed] [Google Scholar]
  • 32.Key TJ, Silcocks PB, Davey GK, Appleby PN, Bishop DT. A case-control study of diet and prostate cancer. Br J Cancer. 1997;76:678–687. doi: 10.1038/bjc.1997.445. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 33.Ghadirian P, Lacroix A, Maisonneuve P, Perret C, Drouin G, Perrault JP, et al. Nutritional factors and prostate cancer: a case-control study of French Canadians in Montreal, Canada. Cancer Causes Control. 1996;7:428–436. doi: 10.1007/BF00052669. [DOI] [PubMed] [Google Scholar]
  • 34.Sinha R, Park Y, Graubard BI, Leitzmann MF, Hollenbeck A, Schatzkin A, et al. Meat and meat-related compounds and risk of prostate cancer in a large prospective cohort study in the United States. Am J Epidemiol. 2009;170:1165–1177. doi: 10.1093/aje/kwp280. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 35.Leitzmann MF, Stampfer MJ, Michaud DS, Augustsson K, Colditz GC, Willett WC, et al. Dietary intake of n-3 and n-6 fatty acids and the risk of prostate cancer. Am J Clin Nutr. 2004;80:204–216. doi: 10.1093/ajcn/80.1.204. [DOI] [PubMed] [Google Scholar]
  • 36.Andersson SO, Wolk A, Bergstrom R, Giovannucci E, Lindgren C, Baron J, et al. Energy, nutrient intake and prostate cancer risk: a population-based case-control study in Sweden. Int J Cancer. 1996;68:716–722. doi: 10.1002/(SICI)1097-0215(19961211)68:6<716::AID-IJC4>3.0.CO;2-6. [DOI] [PubMed] [Google Scholar]
  • 37.Hodge AM, English DR, McCredie MR, Severi G, Boyle P, Hopper JL, et al. Foods, nutrients and prostate cancer. Cancer Causes Control. 2004;15:11–20. doi: 10.1023/B:CACO.0000016568.25127.10. [DOI] [PubMed] [Google Scholar]
  • 38.Gann PH, Hennekens CH, Sacks FM, Grodstein F, Giovannucci EL, Stampfer MJ. Prospective study of plasma fatty acids and risk of prostate cancer. J Natl Cancer Inst. 1994;86:281–286. doi: 10.1093/jnci/86.4.281. [DOI] [PubMed] [Google Scholar]
  • 39.Harvei S, Bjerve KS, Tretli S, Jellum E, Robsahm TE, Vatten L. Prediagnostic level of fatty acids in serum phospholipids: omega-3 and omega-6 fatty acids and the risk of prostate cancer. Int J Cancer. 1997;71:545–551. doi: 10.1002/(sici)1097-0215(19970516)71:4<545::aid-ijc7>3.0.co;2-u. [DOI] [PubMed] [Google Scholar]
  • 40.Newcomer LM, King IB, Wicklund KG, Stanford JL. The association of fatty acids with prostate cancer risk. Prostate. 2001;47:262–268. doi: 10.1002/pros.1070. [DOI] [PubMed] [Google Scholar]
  • 41.Chavarro JE, Stampfer MJ, Li H, Campos H, Kurth T, Ma J. A prospective study of polyunsaturated fatty acid levels in blood and prostate cancer risk. Cancer Epidemiol Biomarkers Prev. 2007;16:1364–1370. doi: 10.1158/1055-9965.EPI-06-1033. [DOI] [PubMed] [Google Scholar]
  • 42.Park SY, Wilkens LR, Henning SM, Le Marchand L, Gao K, Goodman MT, et al. Circulating fatty acids and prostate cancer risk in a nested case-control study: the Multiethnic Cohort. Cancer Causes Control. 2009;20:211–223. doi: 10.1007/s10552-008-9236-4. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 43.Terry P, Lichtenstein P, Feychting M, Ahlbom A, Wolk A. Fatty fish consumption and risk of prostate cancer. Lancet. 2001;357:1764–1766. doi: 10.1016/S0140-6736(00)04889-3. [DOI] [PubMed] [Google Scholar]
  • 44.Augustsson K, Michaud DS, Rimm EB, Leitzmann MF, Stampfer MJ, Willett WC, et al. A prospective study of intake of fish and marine fatty acids and prostate cancer. Cancer Epidemiol Biomarkers Prev. 2003;12:64–67. [PubMed] [Google Scholar]
  • 45.Wallstrom P, Bjartell A, Gullberg B, Olsson H, Wirfalt E. A prospective study on dietary fat and incidence of prostate cancer (Malmo, Sweden) Cancer Causes Control. 2007;18:1107–1121. doi: 10.1007/s10552-007-9050-4. [DOI] [PubMed] [Google Scholar]
  • 46.Chavarro JE, Stampfer MJ, Campos H, Kurth T, Willett WC, Ma J. A prospective study of trans-fatty acid levels in blood and risk of prostate cancer. Cancer Epidemiol Biomarkers Prev. 2008;17:95–101. doi: 10.1158/1055-9965.EPI-07-0673. [DOI] [PubMed] [Google Scholar]
  • 47.Boisire C, Stampfer MJ, Subar AF, Park Y, Kirkpatrick SI, Chiuve SE, et al. Index-based dietary patterns and the risk of prostate cancer in the National Institutes of Health (NIH)-AARP Diet and Health Study. Am J Epidemiol. 2012 doi: 10.1093/aje/kws261. In press. [DOI] [PMC free article] [PubMed] [Google Scholar]

Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Supplementary Materials

1
NIHMS440835-supplement-1.doc (289.5KB, doc)

RESOURCES