Meta-Analysis of Long-Chain Omega-3 Polyunsaturated Fatty Acids (LCω-3PUFA) and Prostate Cancer

Figures & data

TABLE 1 Characteristics of the prospective cohorts and nested case-control studies included in the meta-analysis

Study	Cohort	Age, y	Country	Follow-up, y	LCω-3PUFAs examined	Year LCω-3PUFAs assessed	LCω-3PUFAs assessment method	Sample size	Outcome(s)
Studies using self-reported dietary intakes
Augustsson, 2003	HPFS	40–75	U.S.	12	Total	1986	FFQ	47,882	Advanced
Basset, 2013	MCCS	27–80	Australia	8.9	EPA, DHA, DPA	1990	FFQ	1717/464	Total
Chavarro, 2008	PHS	40–84	U.S.	19	Total	1982	FFQ	20,167	Total, fatal
Crowe, Key 2008	EPIC	50–69	8 European Countries	8.7	Total	1992	FFQ or diet history	142,520	Total, nonadvanced, advanced, low-grade, high-grade
Epstein, 2012	Swedish Cohort	≤80	Sweden	20	Total, EPA, DHA, DPA	1989	FFQ	525	Total, nonadvanced, advanced
Giovannucci, 1993	HPFS	40–75	U.S.	5	Total	1986	FFQ	47,855	Advanced
Koralek, 2006	PLCO	55–74	U.S.	5.1	Total	1993	FFQ	29,592	Total
Kristal, 2010	PCPT	≥55	U.S. + Canada	7	Total	1994	FFQ + supplement use questionnaire	9,559	Low-grade, high-grade
Leitzmann, 2004	HPFS	40–75	US	14	Total, EPA, DHA	1986	FFQ	47,886	Total, nonadvanced, advanced
Männisto, 2003^e	ATBC	50–69	Finland	8	EPA, DHA	1985	FFQ	198/198	Total
Park, 2007	MEC	≥45	U.S.	8	EPA, DHA	1993	FFQ	82,483	Total, advanced
Schuurman, 1999	NLCS	55–69	The Netherlands	6.3	EPA, DHA	1986	FFQ	1525/642	Total, nonadvanced, advanced
Torfadottir, 2013	AGES-Reykjavik	67–96	Iceland	5.1	Total	2002	FFQ	2,268	Total, nonadvanced, advanced
Wallstrom, 2007	MDC	45–73	Sweden	11	Total, EPA, DHA	1991	Diet history	10,564	Total, advanced
Studies using biomarkers of intake
Bassett, 2013	MCCS	27–80	Australia	8.9	EPA, DHA, DPA	1990	Plasma PL FA	1717/464	Total
Brasky, 2011	PCPT	55–84	U.S.	7	Total, EPA, DHA	1994	Serum PL FA	1803/1658	Total, low-grade, high-grade
Brasky, 2013	SELECT	≥50	U.S.	6	Total, EPA, DHA	2001	Plasma PL FA	1393/834	Total, low-grade, high-grade
Chavarro, 2007	PHS	40–84	U.S.	13	Total, EPA, DHA, DPA	1982	Whole blood FA	476/476	Total, nonadvanced, advanced, low-grade, high-grade
Cheng, 2013	CARET	45–69	U.S.	20	Total, EPA, DHA, DPA	1985	Serum PL FA	1398/641	Nonadvanced, advanced
Crowe, Allen 2008	EPIC	35–70	8 European countries	4.2	EPA, DHA, DPA	1992	Plasma PL FA	1061/962	Total, nonadvanced, low-grade
Harvei, 1997	Norway cohort	50 (mean)	Norway	11.6	EPA, DHA, DPA	1973	Serum PL FA	282/141	Total
Männisto, 2003	ATBC	50–69	Finland	8	EPA, DHA	1985	Serum cholesterol FA	198/198	Total
Park, 2009	MEC	45–75	U.S.	1.9	EPA, DHA, DPA	2001	RBC membrane FA	729/376	Total, advanced

AGES-Reykjavik = Age, Gene/Environment Susceptibility-Reykjavik Study; ATBC = Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study; CARET = Carotene and Retinol Efficacy Trial; DHA = docosahexaenoic acid; DPA = docosapentaenoic acid; EPA = eicosapentaenoic acid; EPIC = European Prospective Investigation into Cancer and Nutrition; FA = fatty acid; FFQ = food frequency questionnaire; HPFS = Health Professionals Follow-up Study; MCCS = Melbourne Collaborative Cohort Study; MDC = Malmö Diet and Cancer Study; MEC = Multiethnic Cohort Study; NLCS = Netherlands Cohort Study; PCPT = Prostate Cancer Prevention Trial; PHS = Physician's Health Study; PL = phospholipid; PLCO = Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial; RBC = red blood cell; SELECT = Selenium and Vitamin E Cancer Prevention Trial.

^a Mean provided when age range was not reported.

^b Sample size for nested case-control studies are shown as controls/cases.

^c Basset et al. (2013) investigated associations between fatty acids assessed in plasma phospholipids or diet and prostate cancer risk.

^d Kristal et al. (2010) assessed EPA and DHA intake using an FFQ and structured supplement-use questionnaire.

^e Männisto et al. (2003) evaluated both serum and dietary fatty acids.

^f Torfadottir et al. (2013) evaluated fish liver oil supplements in liquid or capsules.

^g Wallstrom et al. (2007) evaluated EPA and DHA from both diet and supplement use.

TABLE 2 Summary of meta-analysis results for long chain omega-3 polyunsaturated fatty acids and prostate cancer (high vs. low exposure)

Model (number of data points)	SRRE	95% CI	P value for Heterogeneity and I^2
Studies using self-reported dietary intakes
All studies (n = 13)	1.00	0.93–1.09	0.019, I^2 = 50.4
Studies conducted in North America (n = 7)	1.02	0.96–1.09	0.298, I^2 = 17.3
Studies conducted in Europe and Australia (n = 6)	0.94	0.76–1.16	0.006, I^2 = 69.5
Initial dietary assessment period <1990 (n = 6)	0.96	0.82–1.12	0.033, I^2 = 58.7
Initial dietary assessment period 1990+ (n = 7)	1.03	0.93–1.14	0.072, I^2 = 48.2
Follow-up period <10 years (n = 9)	1.01	0.94–1.08	0.334, I^2 = 12.1
Follow-up period 10+ years (n = 4)	0.96	0.77–1.21	0.002, I^2 = 80.1
Nonadvanced prostate cancer (n = 3)	0.91	0.96–1.09	0.533
Advanced prostate cancer (n = 6)	0.83	0.67–1.04	0.078
EPA and total prostate cancer (n = 7)	0.96	0.84–1.10	0.033, I^2 = 56.3
DHA and total prostate cancer (n = 7)	0.97	0.84–1.12	0.023, I^2 = 59.2
DPA and total prostate cancer (n = 2)	0.92	0.71–1.19	0.487, I^2 = 0.0
Studies using biomarkers of intake
All studies (n = 10)	1.07	0.94–1.20	0.065, I^2= 44.0
Studies conducted in North America (n = 6)	1.08	0.89–1.30	0.043, I^2 = 56.4
Studies conducted in Europe and Australia (n = 4)	1.05	0.89–1.23	0.228, I^2 = 30.8
Initial dietary assessment period <1990 (n = 5)	0.93	0.75–1.14	0.222, I^2 = 30.0
Initial dietary assessment period 1990+ (n = 5)	1.14	1.01–1.30	0.159, I^2 = 39.3
Follow-up period <10 years (n = 6)	1.12	0.99–1.27	0.157, I^2 = 37.4
Follow-up period 10+ years (n = 4)	0.93	0.71–1.22	0.131, I^2 = 46.7
Non-advanced prostate cancer (n = 3)	0.96	0.65–1.41	0.054, I^2 = 65.7
Advanced prostate cancer (n = 3)	0.98	0.68–1.42	0.524, I^2 = 0.0
Low-grade prostate cancer (n = 6)^,	1.12	0.96–1.32	0.139, I^2 = 40.0
High-grade prostate cancer (n = 6)^,	1.21	0.83–1.75	0.037, I^2 = 57.7
EPA and total prostate cancer (n = 8)	1.07	0.93–1.23	0.230
DHA and total prostate cancer (n = 8)	1.06	0.87–1.29	0.018
DPA and total prostate cancer (n = 7)	0.85	0.72–0.99	0.764, I^2 = 0.0

SRRE = summary relative risk estimates; CI = confidence interval; EPA = eicosapentaenoic acid; DHA = docosahexaenoic acid; DPA = docosapentaenoic acid.

^a Park et al. (22) was contacted to obtain risk estimates for advanced prostate cancer.

^b Park et al. (22) was contacted to obtain risk estimates for low-grade and high-grade prostate cancer.

^c Risk estimates from correspondence with Bassett et al. for low-grade and high-grade prostate cancer.

FIG. 1. Omega-3 long chain-polyunsaturated fatty acids and total prostate cancer: dietary intake studies, overall and by follow-up duration.

FIG. 2. Omega-3 long chain-polyunsaturated fatty acids and total prostate cancer: biomarker studies, overall and by follow-up duration.

FIG. 3. Omega-3 long chain-polyunsaturated fatty acids and total prostate cancer by grade: biomarker studies.

Park SY, Wilkens LR, Henning SM, Le Marchand L, Gao K, et al.: Circulating fatty acids and prostate cancer risk in a nested case-control study: the Multiethnic Cohort. Cancer Causes Control 20, 211–223, 2009.

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