A high ratio of dietary n-6/n-3 polyunsaturated fatty acids is associated with increased risk of prostate cancer
Introduction
Prostate cancer is the most commonly diagnosed cancer among men in the United States [1], and dietary factors are thought to play a role in prostate cancer development [2]. There is limited evidence that total fat is a risk factor for prostate cancer [3], and evidence for an association between specific fatty acids and prostate cancer development or progression is conflicting [4], [5], [6], [7], [8], [9], [10]. The 2 classes of essential fatty acids are omega-3 (n-3) and omega-6 (n-6) polyunsaturated fatty acids (PUFAs). Polyunsaturated fatty acids are substrates for eicosanoid synthesis, with n-6 fatty acids being converted into proinflammatory eicosanoids and n-3 PUFA being converted to anti-inflammatory eicosanoids [4], [11]. Animal and in vitro studies suggest that n-3 and n-6 PUFA have opposite effects on cancer development: n-3 fatty acids, such as eicosapentaenoic acid (EPA) and docosahexanoic acid (DHA), suppress tumor carcinogenesis, whereas n-6 PUFA promote development [12]. However, results from epidemiologic studies, in general, have not confirmed these findings, with many finding no association between prostate cancer risk and intake of n-3 or n-6 PUFA [4], [5], [6], [7], [8].
One explanation for inconsistent findings among studies is that the balance of n-3 to n-6 PUFA may be more relevant for prostate cancer risk than absolute intakes of these fatty acids [13], [14]. The recommended dietary ratio of n-6/n-3 fatty acids for health benefits is 1:1-2:1 [15], yet the typical Western diet often contains 10 or more times the amount of n-6 relative to n-3 PUFA [16]. Alternatively, the relationship between diet and prostate cancer may differ according to race and ethnicity. Prostate cancer incidence and mortality rates are highest among black men [1], yet few studies have focused on race-specific associations between diet and prostate cancer risk. Dietary factors may also have stronger associations for more aggressive prostate cancers [9], [17], and this finding would be missed when all prostate cancers are combined.
The objectives of this study were to examine the relationship between prostate cancer risk and n-3 and n-6 PUFA intake, and the dietary ratio of n-6/n-3 fatty acids using a case-control study in veterans and to determine whether these associations vary by disease aggressiveness and race. Based on experimental evidence, we hypothesized that high intake of n-3 PUFA will be associated with lower risk of prostate cancer, whereas increased intake of n-6 PUFA will correlate with elevated prostate cancer risk.
Section snippets
Study design and participants
Data collection methods have been described elsewhere [18]. Briefly, men who had been screened for prostate cancer in the last 12 months were recruited to participate in an ongoing case-control study at the Durham Veterans Affairs Medical Center (DVAMC) in Durham, NC, from January 2007 to November 2009. Cases were men 18 years or older with no history of prostate cancer who were scheduled for a prostate needle biopsy at the urology clinic. Of the 485 eligible cases, 450 consented to
Results
Compared with controls, prostate cancer cases were more likely to have a lower BMI (P =.03), and a higher proportion of cases had a family history of prostate cancer (P =.06; Table 1). The median prostate-specific antigen (PSA) level was also higher in cases than controls (P <.0001). There were no differences in age, education, or smoking status between cases and controls. There was also no difference between cases and controls for daily mean intakes of total energy and PUFA, and the average
Discussion
In this case-control study, intakes of total, n-3, and n-6 PUFA were not associated with prostate cancer risk. In whites, a high dietary ratio of n-6/n-3 fatty acids was suggestive of higher prostate cancer risk, yet there was a practically null association between the dietary ratio of n-6/n-3 fatty acids and prostate cancer risk in blacks. Among all men, there was evidence of a strong positive association and significant trend between the dietary ratio of n-6/n-3 fatty acids and high-grade
Acknowledgment
This work was supported by the Agency for Healthcare Research and Quality (T32 HS00079), National Institutes of Health NCMHC (P20 MD000175), Department of Defense (PC060233), Department of Veterans Affairs, and the American Urological Association Foundation/Astellas Rising Star in Urology.
References (47)
- et al.
Intakes of fish and marine fatty acids and the risks of cancers of the breast and prostate and of other hormone-related cancers: a review of the epidemiologic evidence
Am J Clin Nutr
(2003) Omega-3 PUFA: good or bad for prostate cancer?
Prostaglandins Leukot Essent Fatty Acids
(2008)- et al.
The relation of alpha-linolenic acid to the risk of prostate cancer: a systematic review and meta-analysis
Am J Clin Nutr
(2009) - et al.
Dietary long-chain n-3 fatty acids for the prevention of cancer: a review of potential mechanisms
Am J Clin Nutr
(2004) - et al.
Prostate tumor growth can be modulated by dietarily targeting the 15-lipoxygenase-1 and cyclooxygenase-2 enzymes
Neoplasia
(2009) - et al.
Exercise and prostate cancer risk in a cohort of veterans undergoing prostate needle biopsy
J Urol
(2009) - et al.
Polyunsaturated fatty acids in the food chain in the United States
Am J Clin Nutr
(2000) Effects of dietary fatty acids on breast and prostate cancers: evidence from in vitro experiments and animal studies
Am J Clin Nutr
(1997)- 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) - et al.
Prostate tumor growth and recurrence can be modulated by the omega-6:omega-3 ratio in diet: athymic mouse xenograft model simulating radical prostatectomy
Neoplasia
(2006)
Growth inhibitory effect of low fat diet on prostate cancer cells: results of a prospective, randomized dietary intervention trial in men with prostate cancer
J Urol
A 22-y prospective study of fish intake in relation to prostate cancer incidence and mortality
Am J Clin Nutr
Dietary intake of n-3 and n-6 fatty acids and the risk of prostate cancer
Am J Clin Nutr
Fatty fish consumption and risk of prostate cancer
Lancet
Cancer Facts & Figures 2009
Impact of diet on prostate cancer: a review
Prostate Cancer Prostatic Dis
Food, nutrition, physical activity and the prevention of cancer: a global perspective
Dietary N-6 and N-3 polyunsaturated fatty acids and prostate cancer risk: a review of epidemiological and experimental evidence
Cancer Causes Control
Circulating fatty acids and prostate cancer risk in a nested case-control study: the Multiethnic Cohort
Cancer Causes Control
A prospective study of polyunsaturated fatty acid levels in blood and prostate cancer risk
Cancer Epidemiol Biomarkers Prev
Biomarkers of essential fatty acid consumption and risk of prostatic carcinoma
Cancer Epidemiol Biomarkers Prev
Dietary fatty acids and prevention of hormone-responsive cancer
Proc Soc Exp Biol Med
Effect of altering dietary omega-6/omega-3 fatty acid ratios on prostate cancer membrane composition, cyclooxygenase-2, and prostaglandin E2
Clin Cancer Res
Cited by (144)
Nutritional value of different parts from sea eel (Astroconger myriaster) determined by untargeted-lipidomic approach
2023, Food Research InternationalFatty acids and their lipid mediators in the induction of cellular apoptosis in cancer cells
2022, Prostaglandins and Other Lipid Mediators