Article Figures & Data
Figures
- Figure 1.
Flow chart of study selection. The flow chart shows the process used to select prospective studies for the meta-analysis of the association between n-3 PUFAs and the risk of colorectal cancer.
- Figure 2.
A, Forest plot of prospective studies of colorectal cancer for the highest versus lowest category of n-3 PUFA intake, using a random-effects model. The sizes of the squares correspond to the inverse of the variance of the natural logarithm of the RR from each prospective study, and the diamond indicates the pooled RR. B, Pooled dose–response association between n-3 PUFA intake and colorectal cancer. Data were modeled with random-effects restricted cubic spline models with 3 knots. The vertical axis is on a log scale.
- Figure 3.
Pooled dose–response associations of EPA, DHA, DPA, and ALA intake with colorectal cancer. Data were modeled with random-effects restricted cubic spline models with 3 knots. The vertical axis is on a log scale.
- Figure 4.
Forest plot of prospective studies of colorectal cancer for the highest versus lowest category of blood levels of n-3 PUFAs using a random-effects model. The sizes of the squares correspond to the inverse of the variance of the natural logarithm of the RR from each prospective study, and the diamond indicates the pooled RR.
Tables
- Table 1.
Characteristics of prospective studies included in the meta-analysis of n-3 PUFAs and colorectal cancer.
First Age at Study size author, year Country Cohort name Follow-up period baseline, years Subjects No. of cases Sex of subjects Exposure Adjustment for covariates Bostick, 1994 United States The Iowa Women's Health Study 5 years 55–69 35,215 212 Female n-3 PUFA intake Age, total energy intake, height, parity, total vitamin E intake, a total vitamin E by age interaction term, and vitamin A supplement intake Pietinen, 1999 Finland The Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study 8 years 50–69 27,111 185 Male n-3 PUFA intake Age, supplement group, smoking years, BMI, alcohol, education, physical activity at work, and calcium intake Terry, 2001 Sweden The Swedish Mammography Screening Cohort 9.6 years 40–74 61,463 460 Female n-3 PUFA intake Age, BMI, education level, energy intake, intakes of red meat and alcohol, energy, dietary fiber, calcium, vitamin C, folic acid, and vitamin D. Saturated fat, monounsaturated fat, polyunsaturated fat. Kojima, 2005 Japan Japan Collaborative Cohort Study 7.1 years 40–79 650 169 Male and female Blood levels of n-3 PUFAs Family history of colorectal cancer in first-degree relatives, BMI, education, smoking and alcohol drinking history, green leafy vegetable intake, and physical exercise. Cases and controls were matched on age and participating institution. Oba, 2006 Japan A community-based cohort in Japan 7 years ≥35 30,221 203 Male and female n-3 PUFA intake Age, height, BMI, total pack-years of cigarette smoking, alcohol intake, and physical activity Hall, 2007 United States Physicians' Health Study 1982–1995 40–84 460 178 Male Blood levels of n-3 PUFAs BMI, multivitamin use, history of diabetes, random assignment to aspirin or placebo, vigorous exercise, alcohol intake, and quartile of red meat intake. Controls were matched on age and smoking status. Hall, 2008 United States Physicians' Health Study 17.6 years 53.6, mean 21,406 500 Male n-3 PUFA intake Age, smoking, BMI, multivitamin use, history of diabetes, random assignment to aspirin or placebo, vigorous exercise, alcohol intake, and quartile of red meat intake Butler, 2009 Singapore Singapore Chinese Health Study 9.8 years 45–74 61,321 961 Male and female n-3 PUFA intake Age at interview, sex, dialect group (Cantonese, Hokkien), interview year, diabetes at baseline, smoking history, BMI, alcohol intake, education, any weekly physical activity, first-degree relative diagnosed with colorectal cancer, and total daily energy intake Murff, 2009 China Shanghai Women's Health Study 1996–2007 40–70 73,242 396 Female n-3 PUFA intake Age, energy intake, total energy-adjusted n-6 PUFA intake, energy-adjusted ratio of total n-6 PUFA to n-3 PUFA intake, BMI, current smoker, alcohol use, regular physical activity in past 5 y, total energy-adjusted red meat intake, menopausal status, hormone replacement therapy use, multivitamin use, and aspirin use Daniel, 2009 United States Cancer Prevention Study-II Nutrition Cohort 6 years 70 male 68 female, mean 99,080 869 Male and female n-3 PUFA intake Age, energy, recreational physical activity, NSAID use, colorectal screening, BMI, and red and processed meat, low-fat dairy, fruit, and vegetable intake Sasazuki, 2011 Japan The Japan Public Health Center 9.3 years 40–69 98,466 1,268 Male and female n-3 PUFA intake Age, area, BMI, smoking status, alcohol drinking, past history of or medication use for diabetes mellitus, METs, screening for colorectal cancer, total calorie, intake of calcium, vitamin D, fiber, and red meat Key, 2012 United Kingdom UK Dietary Cohort Consortium 1985–2006 61.7, mean 2,415 547 Male and female n-3 PUFA intake Age, date of diary, sex, height, weight, energy intake, alcohol intake, fiber intake, smoking, education, social class, physical activity Kantor, 2014 United States VITamins And Lifestyle Study 6.7 years 50–76 68,109 488 Male and female n-3 PUFA intake Age, sex, race/ethnicity, education, BMI, energy intake, MET-hr per wk of moderate/vigorous activity, alcohol intake, smoking history, multivitamin use, calcium intake, dietary fiber intake, fruit and vegetable intake, red/processed meat intake, aspirin use, nonaspirin NSAID drug use, family history of colorectal cancer, history of sigmoidoscopy/colonoscopy, history of polyps, hormone replacement therapy, cardiovascular disease, memory loss, use of cholesterol-lowering drugs, and omega-6 (linoleic +arachidonic) intake Song, 2014 United States Nurses' Health Study 24 years 30–55 76,386 1,469 Female n-3 PUFA intake Age, calendar year, family history of colorectal cancer, prior lower gastrointestinal endoscopy, pack-years of smoking before age 30, BMI, physical activity, current multivitamin use, postmenopausal status and hormone use, regular aspirin or NSAID use, total caloric intake, red meat, processed meat, alcohol consumption, energy-adjusted intake of folate, calcium, vitamin D, and total fiber Song, 2014 United States Health Professionals Follow-up Study 26 years 40–75 47,143 987 Male n-3 PUFA intake Age, calendar year, family history of colorectal cancer, prior lower gastrointestinal endoscopy, pack-years of smoking before age 30, BMI, physical activity, current multivitamin use, regular aspirin or NSAID use, total caloric intake, red meat, process meat, alcohol consumption and energy-adjusted intake of folate, calcium, vitamin D, and total fiber Hodge, 2015 Australia Melbourne Collaborative Cohort Study 9 years 40–69 41,514 395 Male and female n-3 PUFA intake; blood levels of n-3 PUFAs Age, education, alcohol intake, smoking status, physical activity, total energy intake and stratified by: sex, ethnicity (Southern-European migrant vs. not), and family history of cancer Kraja, 2015 Netherlands Rotterdam Study 14.6 years ≥55 4,967 222 Male and female n-3 PUFA intake Age, sex, energy-adjusted dietary fiber intake, intake of vegetable, trans fat, fruit, alcohol, and sodium Navarro, 2016 United States Women's Health Initiative prospective cohort 11.7 years 50–79 134,017 1,952 Female n-3 PUFA intake Age, total energy intake, BMI, education, family history of colorectal cancer, history of colonoscopy, current NSAID use, alcohol intake, smoking history, physical activity, ever use of hormone therapy, folate, calcium, and red meat intake, study component, randomization assignment and treatment arm Butler, 2017 Singapore Singapore Chinese Health Study 3.3 years 45–74 700 350 Male and female Blood levels of n-3 PUFAs BMI, smoking, education level, alcohol use, weekly physical activity, history of diabetes, and use of NSAIDs. The control was matched to an index case by sex, dialect group, age, date of baseline interview, and date of biospecimen collection. Aglago, 2019 Europe European Prospective Investigation into Cancer and Nutrition 14.9 years 51.3, mean 476,160 6,291 Male and female n-3 PUFA intake; blood levels of n-3 PUFAs Age, sex, center, BMI, height, physical activity, smoking, education, and intakes of energy, alcohol, red and processed meat, fiber, dairy products Abbreviations: MET, metabolic equivalent; No., number.
- Table 2.
Summary of pooled RRs of colorectal cancer risk for n-3 PUFAs.
Variable No. of studies RR 95% CI P for difference n-3 PUFA intake High versus low n-3 fatty acid intake All studies 17 0.97 0.90–1.04 Sex Male 8 0.95 0.84–1.06 0.59 Female 10 0.99 0.89–1.09 Geographic region United States 7 0.95 0.84–1.07 Europe 5 0.98 0.83–1.15 0.83a Asia 4 1.01 0.88–1.16 0.59a Oceania 1 1.07 0.76–1.50 0.59a Cancer sites Colon 9 0.94 0.83–1.06 0.49b Proximal 4 0.84 0.72–1.00 0.11c Distal 4 1.12 0.84–1.48 Rectal 7 0.98 0.87–1.11 Duration of follow-up <Median 9 0.98 0.86–1.11 0.89 ≥Median 8 0.96 0.88–1.05 Type of fatty acids ALA 7 1.01 0.92–1.12 EPA 5 0.89 0.80–0.99 0.04d DHA 5 0.88 0.81–0.96 0.05d DPA 3 0.87 0.74–1.03 0.01d Quality score <10 2 0.92 0.54–1.56 0.79 ≥10 15 0.97 0.90–1.04 Adjustment for age, BMI, smoking, alcohol, and physical activity Yes 11 0.95 0.88–1.01 0.79 No 6 0.99 0.82–1.19 Increase of g/day in n-3 PUFA intake n-3 PUFA, 0.5 g/day 13 1.00 0.97–1.03 ALA, 0.1 g/day 5 1.00 0.996–1.01 EPA, 0.1 g/day 3 0.95 0.92–0.98 DHA, 0.1 g/day 3 0.97 0.95–0.99 DPA, 0.1 g/day 2 0.87 0.73–1.03 Blood levels of n-3 PUFAs High versus low blood levels of n-3 fatty acids All studies 5 0.79 0.64–0.98 Sex Male 2 0.41 0.18–0.94 0.49 Female 1 0.85 0.38–1.91 Geographic region Asia 2 0.76 0.50–1.15 0.98 Non-Asia 3 0.80 0.62–1.02 Cancer sites Colon 2 0.81 0.62–1.06 0.47 Rectal 1 1.08 0.69–1.67 Duration of follow-up <Median 3 0.73 0.51–1.05 0.75 ≥Median 2 0.83 0.64–1.08 Type of fatty acids ALA 3 0.88 0.49–1.58 EPA 5 0.82 0.67–1.00 0.75e DHA 5 0.80 0.61–1.06 0.77e DPA 3 0.72 0.46–1.12 0.60e Quality score <10 2 0.81 0.59–1.11 0.87 ≥10 3 0.75 0.53–1.08 Adjustment for age, BMI, smoking, alcohol, and physical activity Yes 3 0.67 0.41–1.10 0.70 No 2 0.82 0.66–1.01 Increase of 1% in blood levels of n-3 PUFAs All studies 3 0.96 0.92–1.00 Abbreviation: No., number.
↵aP value difference in RRs of n-3 PUFA intake for Europe versus United States (P = 0.83), Asia versus United States (P = 0.59), and Oceania versus United States (P = 0.59).
↵bP value difference in RRs of n-3 PUFA intake for rectal cancer versus colon cancer.
↵cP value difference in RRs of n-3 PUFA intake for distal colon cancer versus proximal colon cancer.
↵dP value difference in RRs of n-3 PUFA intake for EPA versus ALA (P = 0.04), DHA versus ALA (P = 0.05), and DPA versus ALA (P = 0.01).
↵eP value difference in RRs of blood levels of n-3 PUFAs for EPA versus ALA (P = 0.75), DHA versus ALA (P = 0.77), and DPA versus ALA (P = 0.60).
Supplementary Data
- Supplementary Tables 1-2 and Figure 1. - Supplementary Table 1. Search terms for literature search. Supplementary Table 2. Summary of pooled relative risks (RR) of colorectal cancer risk for marine n-3 PUFAs.Supplementary Figure 1. Pooled dose-response association between marine n-3 PUFA intake and colorectal cancer.
February 2020
Volume 29, Issue 2
Volume 29, Issue 2
Intake or Blood Levels of n-3 Polyunsaturated Fatty Acids and Risk of Colorectal Cancer: A Systematic Review and Meta-analysis of Prospective Studies
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