Elsevier

Nutrition Research

Volume 31, Issue 1, January 2011, Pages 1-8
Nutrition Research

A high ratio of dietary n-6/n-3 polyunsaturated fatty acids is associated with increased risk of prostate cancer

https://doi.org/10.1016/j.nutres.2011.01.002Get rights and content

Abstract

Experimental studies suggest omega-3 (n-3) polyunsaturated fatty acids (PUFA) suppress and n-6 PUFA promote prostate tumor carcinogenesis. Epidemiologic evidence remains inconclusive. The objectives of this study were to examine the association between n-3 and n-6 PUFA and prostate cancer risk and determine if these associations differ by race or disease aggressiveness. We hypothesize that high intakes of n-3 and n-6 PUFA will be associated with lower and higher prostate cancer risk, respectively. A case-control study comprising 79 prostate cancer cases and 187 controls was conducted at the Durham VA Medical Center. Diet was assessed using a food frequency questionnaire. Logistic regression analyses were used to obtain odds ratios (ORs) and 95% confidence intervals (95% CI) for the associations between n-3 and n-6 PUFA intakes, the dietary ratio of n-6/n-3 fatty acids, and prostate cancer risk. Our results showed no significant associations between specific n-3 or n-6 PUFA intakes and prostate cancer risk. The highest dietary ratio of n-6/n-3 was significantly associated with elevated risk of high-grade (OR, 3.55; 95% CI, 1.18-10.69; Ptrend = 0.03), but not low-grade prostate cancer (OR, 0.95; 95% CI, 0.43-2.17). In race-specific analyses, an increasing dietary ratio of n-6/n-3 fatty acids correlated with higher prostate cancer risk among white men (Ptrend = 0.05), but not black men. In conclusion, our findings suggest that a high dietary ratio of n-6/n-3 fatty acids may increase the risk of overall prostate cancer among white men and possibly increase the risk of high-grade prostate cancer among all men.

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.

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