Background: Higher intake of long-chain ω-3 polyunsaturated fatty acids and nuts, rich plant sources of unsaturated fats, after colon cancer diagnosis are associated with improved survival. It is not known whether the amount or the distribution of other types of fat is associated with survival after colon cancer.

Methods: We prospectively examined postdiagnostic total, animal, and vegetable fats, as well as the saturated, monounsaturated, polyunsaturated, and trans fat in relation to disease-free survival among 1,011 patients with stage III colon cancer. Patients were enrolled between 1999 and 2001 at the onset of adjuvant chemotherapy and followed for recurrence or death through 2009.

Results: During median follow-up of 7 years, we observed 305 deaths and 81 recurrences (total events: 386). Neither total nor any specific type of dietary fat examined was statistically significantly associated with risk of cancer recurrence or death from any cause (disease-free survival) after stage III colon cancer.

Conclusions: The amount and type (animal, vegetable, saturated, monounsaturated, polyunsaturated, and trans) of dietary fat consumed after colon cancer does not appear to be substantially associated with risk of recurrence or survival.

Impact: Neither total nor major types (animal, vegetable, saturated, monounsaturated, polyunsaturated, and trans) of dietary fat consumed after colon cancer was associated with cancer recurrence or survival. Cancer Epidemiol Biomarkers Prev; 27(10); 1227–30. ©2018 AACR.

More than 1.3 million Americans live with colorectal cancer. Data from our group suggest that marine ω-3 polyunsaturated fatty acids and nuts, plant sources of unsaturated fat, may reduce risk of death from colon cancer (1, 2). However, it is unknown whether the total amount, or major types (animal, vegetable, saturated, monounsaturated, polyunsaturated, and trans), of dietary fat are associated with colon cancer survival. Thus, we prospectively examined dietary fat and disease-free survival among patients with colon cancer. We hypothesized that high vegetable fat and low animal fat intake would be associated with longer disease-free survival.

This study was conducted among 1,095 patients with stage III colon cancer enrolled in a chemotherapy trial [Cancer and Leukemia Group B (CALGB) 89803] between 1999 and 2001 who completed a lifestyle survey, as described previously (3, 4). CALGB is now part of the Alliance for Clinical Trials in Oncology. Informed written consent was obtained from all the patients; the study was institutional review board approved and conducted in accordance with recognized ethical guidelines.

We excluded 8 patients who recurred prior to the survey, 30 who recurred or died within 90 days of the survey, and 46 who reported implausible energy (<600 or >4,200 kcal/day for men, <500 or >3,200 kcal/day for women) or left ≥70 survey items blank, leaving 1,011 eligible patients.

Diet was assessed via food frequency questionnaire (FFQ) during and after 6 months of therapy (∼3 and 15 months after diagnosis; ref. 5). Exposures of interest included total, animal, and vegetable fat, as well as saturated, monounsaturated, polyunsaturated (total, ω-3, ω-6), and trans fat. Our primary outcome, disease-free survival, was time from the first FFQ to recurrence, new primary colon tumor, or death from any cause.

We examined dietary fats in relation to disease-free survival using Cox proportional hazards regression. We used the nutrient residual method to adjust dietary fat for energy, and calculated postdiagnostic intakes using a weighted average from available surveys (3, 6). Our Model 1 was adjusted for sex, energy (kcal/day), and age at diagnosis (years). Model 2 was additionally adjusted for T-stage (T1-T2, T3-T4, unknown), positive lymph nodes (1–3, ≥4, unknown), performance status (fully active, restricted in strenuous activity, unknown), treatment arm, body mass index (BMI; kg/m2), physical activity (MET-h/wk), smoking (current, past, never, unknown), aspirin use (yes, no, unknown), and intake (g/day) of protein, alcohol, and fats other than the fat of interest. We considered adjustment for other dietary factors, including Western dietary pattern, prudent dietary pattern, folate, vitamin D, and calcium; point estimates did not materially change.

The Alliance Statistics and Data Center collected the data and the database was frozen on November 9, 2009. All statistical analyses were conducted using SAS v. 9.4 and two-sided P values <0.05 were considered statistically significant.

We observed 305 deaths and 81 recurrences (386 total events) among 1,011 patients with colon cancer (median follow-up: 6.6 years). Patients who consumed more vegetable fat were older and consumed less animal fat, carbohydrates, and protein than those who consumed less vegetable fat (Table 1). Quartiles 2 and 3 of vegetable fat were more likely to receive irinotecan than quartiles 1 or 4. Patients who consumed more animal fat were younger, had higher BMI, and consumed less vegetable fat and carbohydrates and more protein compared with patients who consumed less animal fat. Neither total fat nor any type of fat examined (animal, vegetable, saturated, monounsaturated, polyunsaturated, trans) was statistically significantly associated with disease-free survival after colon cancer (Table 2). Post hoc, we estimated that the minimum detectable beneficial HR across extreme quartiles was 0.58 with 80% power, assuming a linear relationship and two-tailed α = 0.05 (7).

Table 1.

Characteristics of 1,011 patients with stage III colon cancer, by postdiagnostic intake of animal and vegetable fat

Quartile of animal fatQuartile of vegetable fat
1414
252 253  252 253  
Characteristic, median (IQR) or %   P   P 
Male 56 60 0.26 54 54 0.20 
Age, years 62 (54–70) 57 (51–67) 0.01 60 (51–69) 62 (54–69) 0.03 
Race   0.14   0.41 
 White 89 86  86 90  
 Black 10   
 Other   
Performance status   0.29   0.40 
 Fully active 76 68  72 73  
 Restricted in strenuous activity 21 30  27 26  
 Unknown   
Bowel wall invasion   0.89   0.87 
 T1–T2 15 14  12 13  
 T3–T4 77 80  83 79  
 Unknown   
Positive lymph nodes   0.65   0.26 
 1–3 (N1) 62 64  67 64  
 ≥4 (N2) 35 34  32 35  
 Unknown   
Clinical bowel abnormality       
 Perforation 0.34 0.10 
 Obstruction 23 25 0.31 22 23 0.32 
Grade of differentiation   0.88   0.26 
 Well   
 Moderate 71 68  68 72  
 Poor 22 24  25 21  
 Unknown   
Treatment arm   0.88   0.006 
 Fluorouracil + leucovorin 51 51  56 57  
 Irinotecan, fluorouracil, leucovorin 49 49  44 43  
Smoking status   0.33   0.94 
 Current 13  12 10  
 Past 48 44  44 43  
 Never 45 42  44 45  
 Unknown   
Aspirin user 0.72 0.73 
BMI, kg/m2 26.7 (23.8–29.9) 29.3 (25.0–33.9) <0.001 27.5 (24.1–32.1) 28.3 (24.7–31.8) 0.26 
Physical activity, MET h/wk 7.7 (2.2–23.2) 5.9 (1.7–16.7) 0.09 7.4 (2.7–18.1) 5.7 (1.6–16.5) 0.11 
Energy, kcal/day 1,848 (1,532–2,327) 1,915 (1,502–2,334) 0.59 1,866 (1,553–2,336) 1,794 (1,457–2,309) 0.29 
Animal fat, g/day 27 (23–29) 50 (47–55) <0.001 39 (31–48) 35 (29–42) <0.001 
Vegetable fat, g/day 34 (28–42) 30 (24–36) <0.001 23 (20–25) 46 (42–52) <0.001 
Carbohydrate, g/day 284 (266–307) 225 (205–241) <0.001 267 (240–293) 237 (213–260) <0.001 
Protein, g/day 76 (66–87) 89 (81–100) <0.001 89 (76–101) 76 (68–86) <0.001 
Quartile of animal fatQuartile of vegetable fat
1414
252 253  252 253  
Characteristic, median (IQR) or %   P   P 
Male 56 60 0.26 54 54 0.20 
Age, years 62 (54–70) 57 (51–67) 0.01 60 (51–69) 62 (54–69) 0.03 
Race   0.14   0.41 
 White 89 86  86 90  
 Black 10   
 Other   
Performance status   0.29   0.40 
 Fully active 76 68  72 73  
 Restricted in strenuous activity 21 30  27 26  
 Unknown   
Bowel wall invasion   0.89   0.87 
 T1–T2 15 14  12 13  
 T3–T4 77 80  83 79  
 Unknown   
Positive lymph nodes   0.65   0.26 
 1–3 (N1) 62 64  67 64  
 ≥4 (N2) 35 34  32 35  
 Unknown   
Clinical bowel abnormality       
 Perforation 0.34 0.10 
 Obstruction 23 25 0.31 22 23 0.32 
Grade of differentiation   0.88   0.26 
 Well   
 Moderate 71 68  68 72  
 Poor 22 24  25 21  
 Unknown   
Treatment arm   0.88   0.006 
 Fluorouracil + leucovorin 51 51  56 57  
 Irinotecan, fluorouracil, leucovorin 49 49  44 43  
Smoking status   0.33   0.94 
 Current 13  12 10  
 Past 48 44  44 43  
 Never 45 42  44 45  
 Unknown   
Aspirin user 0.72 0.73 
BMI, kg/m2 26.7 (23.8–29.9) 29.3 (25.0–33.9) <0.001 27.5 (24.1–32.1) 28.3 (24.7–31.8) 0.26 
Physical activity, MET h/wk 7.7 (2.2–23.2) 5.9 (1.7–16.7) 0.09 7.4 (2.7–18.1) 5.7 (1.6–16.5) 0.11 
Energy, kcal/day 1,848 (1,532–2,327) 1,915 (1,502–2,334) 0.59 1,866 (1,553–2,336) 1,794 (1,457–2,309) 0.29 
Animal fat, g/day 27 (23–29) 50 (47–55) <0.001 39 (31–48) 35 (29–42) <0.001 
Vegetable fat, g/day 34 (28–42) 30 (24–36) <0.001 23 (20–25) 46 (42–52) <0.001 
Carbohydrate, g/day 284 (266–307) 225 (205–241) <0.001 267 (240–293) 237 (213–260) <0.001 
Protein, g/day 76 (66–87) 89 (81–100) <0.001 89 (76–101) 76 (68–86) <0.001 

Abbreviation: MET, metabolic equivalent task.

aP value calculated using χ2 tests for categorical measures and Kruskal–Wallis tests for continuous measures.

Table 2.

Relative risk of cancer recurrence or death from any cause (disease-free survival) among 1,011 patients with colon cancer, by postdiagnostic fat intake

Quartile of intake
1234Ptrenda
Total fat 
 Median, g/day 57 68 76 87  
 Events 96 94 94 102  
 Model 1 HR (95% CI)b 1.00 0.98 (0.74–1.31) 0.99 (0.74–1.31) 1.07 (0.81–1.42) 0.62 
 Model 2 HR (95% CI)c 1.00 1.08 (0.80–1.46) 1.03 (0.76–1.39) 1.10 (0.82–1.49) 0.58 
Animal fat 
 Median, g/day 27 34 41 50  
 Events 108 94 89 95  
 Model 1 HR (95% CI)b 1.00 0.89 (0.67–1.17) 0.78 (0.59–1.03) 0.87 (0.66–1.15) 0.25 
 Model 2 HR (95% CI)c 1.00 0.84 (0.62–1.14) 0.74 (0.54–1.02) 0.78 (0.54–1.14) 0.16 
Vegetable fat 
 Median, g/day 23 30 35 46  
 Events 90 90 101 105  
 Model 1 HR (95% CI)b 1.00 0.99 (0.73–1.32) 1.15 (0.86–1.53) 1.22 (0.92–1.62) 0.11 
 Model 2 HR (95% CI)c 1.00 0.98 (0.72–1.34) 1.09 (0.79–1.49) 1.17 (0.84–1.62) 0.27 
Saturated fat 
 Median, g/day 18 22 25 30  
 Events 96 88 94 108  
 Model 1 HR (95% CI)b 1.00 0.90 (0.67–1.20) 0.95 (0.71–1.26) 1.14 (0.87–1.51) 0.27 
 Model 2 HR (95% CI)c 1.00 0.97 (0.70–1.34) 0.96 (0.68–1.37) 1.15 (0.77–1.72) 0.44 
Monounsaturated fat 
 Median, g/day 21 26 29 34  
 Events 102 102 80 102  
 Model 1 HR (95% CI)b 1.00 0.96 (0.73–1.26) 0.75 (0.56–1.00) 0.99 (0.75–1.30) 0.64 
 Model 2 HR (95% CI)c 1.00 0.92 (0.67–1.26) 0.63 (0.43–0.91) 0.71 (0.46–1.09) 0.08 
Polyunsaturated fat 
 Median, g/day 10 12 14 18  
 Events 101 84 94 107  
 Model 1 HR (95% CI)b 1.00 0.81 (0.60–1.08) 0.90 (0.68–1.19) 1.09 (0.83–1.43) 0.28 
 Model 2 HR (95% CI)c 1.00 0.87 (0.63–1.18) 0.98 (0.71–1.35) 1.25 (0.89–1.75) 0.08 
ω-6 Polyunsaturated fatty acids 
 Median, g/day 11 13 16  
 Events 106 79 95 106  
 Model 1 HR (95% CI)b 1.00 0.70 (0.52–0.94) 0.89 (0.67–1.17) 1.01 (0.78–1.33) 0.46 
 Model 2 HR (95% CI)c 1.00 0.78 (0.57–1.08) 0.97 (0.70–1.35) 1.16 (0.76–1.77) 0.34 
ω-3 Polyunsaturated fatty acidsd 
 Median, g/day 0.9 1.2 1.5 2.0  
 Events 97 92 94 103  
 Model 1 HR (95% CI)b 1.00 0.93 (0.70–1.24) 0.96 (0.72–1.28) 1.11 (0.84–1.46) 0.38 
 Model 2 HR (95% CI)c 1.00 0.80 (0.59–1.08) 0.89 (0.65–1.22) 0.88 (0.59–1.30) 0.65 
Trans fatty acids 
 Median, g/day 1.8 2.4 2.9 3.6  
 Events 99 83 93 111  
 Model 1 HR (95% CI)b 1.00 0.77 (0.57–1.03) 0.85 (0.64–1.13) 1.09 (0.83–1.43) 0.36 
 Model 2 HR (95% CI)c 1.00 0.71 (0.52–0.98) 0.77 (0.55–1.09) 0.93 (0.64–1.36) 0.99 
Quartile of intake
1234Ptrenda
Total fat 
 Median, g/day 57 68 76 87  
 Events 96 94 94 102  
 Model 1 HR (95% CI)b 1.00 0.98 (0.74–1.31) 0.99 (0.74–1.31) 1.07 (0.81–1.42) 0.62 
 Model 2 HR (95% CI)c 1.00 1.08 (0.80–1.46) 1.03 (0.76–1.39) 1.10 (0.82–1.49) 0.58 
Animal fat 
 Median, g/day 27 34 41 50  
 Events 108 94 89 95  
 Model 1 HR (95% CI)b 1.00 0.89 (0.67–1.17) 0.78 (0.59–1.03) 0.87 (0.66–1.15) 0.25 
 Model 2 HR (95% CI)c 1.00 0.84 (0.62–1.14) 0.74 (0.54–1.02) 0.78 (0.54–1.14) 0.16 
Vegetable fat 
 Median, g/day 23 30 35 46  
 Events 90 90 101 105  
 Model 1 HR (95% CI)b 1.00 0.99 (0.73–1.32) 1.15 (0.86–1.53) 1.22 (0.92–1.62) 0.11 
 Model 2 HR (95% CI)c 1.00 0.98 (0.72–1.34) 1.09 (0.79–1.49) 1.17 (0.84–1.62) 0.27 
Saturated fat 
 Median, g/day 18 22 25 30  
 Events 96 88 94 108  
 Model 1 HR (95% CI)b 1.00 0.90 (0.67–1.20) 0.95 (0.71–1.26) 1.14 (0.87–1.51) 0.27 
 Model 2 HR (95% CI)c 1.00 0.97 (0.70–1.34) 0.96 (0.68–1.37) 1.15 (0.77–1.72) 0.44 
Monounsaturated fat 
 Median, g/day 21 26 29 34  
 Events 102 102 80 102  
 Model 1 HR (95% CI)b 1.00 0.96 (0.73–1.26) 0.75 (0.56–1.00) 0.99 (0.75–1.30) 0.64 
 Model 2 HR (95% CI)c 1.00 0.92 (0.67–1.26) 0.63 (0.43–0.91) 0.71 (0.46–1.09) 0.08 
Polyunsaturated fat 
 Median, g/day 10 12 14 18  
 Events 101 84 94 107  
 Model 1 HR (95% CI)b 1.00 0.81 (0.60–1.08) 0.90 (0.68–1.19) 1.09 (0.83–1.43) 0.28 
 Model 2 HR (95% CI)c 1.00 0.87 (0.63–1.18) 0.98 (0.71–1.35) 1.25 (0.89–1.75) 0.08 
ω-6 Polyunsaturated fatty acids 
 Median, g/day 11 13 16  
 Events 106 79 95 106  
 Model 1 HR (95% CI)b 1.00 0.70 (0.52–0.94) 0.89 (0.67–1.17) 1.01 (0.78–1.33) 0.46 
 Model 2 HR (95% CI)c 1.00 0.78 (0.57–1.08) 0.97 (0.70–1.35) 1.16 (0.76–1.77) 0.34 
ω-3 Polyunsaturated fatty acidsd 
 Median, g/day 0.9 1.2 1.5 2.0  
 Events 97 92 94 103  
 Model 1 HR (95% CI)b 1.00 0.93 (0.70–1.24) 0.96 (0.72–1.28) 1.11 (0.84–1.46) 0.38 
 Model 2 HR (95% CI)c 1.00 0.80 (0.59–1.08) 0.89 (0.65–1.22) 0.88 (0.59–1.30) 0.65 
Trans fatty acids 
 Median, g/day 1.8 2.4 2.9 3.6  
 Events 99 83 93 111  
 Model 1 HR (95% CI)b 1.00 0.77 (0.57–1.03) 0.85 (0.64–1.13) 1.09 (0.83–1.43) 0.36 
 Model 2 HR (95% CI)c 1.00 0.71 (0.52–0.98) 0.77 (0.55–1.09) 0.93 (0.64–1.36) 0.99 

Abbreviations: CI, confidence interval; HR, hazard ratio.

aPtrend calculated by modeling the median of each category as a continuous term.

bCox proportional hazards regression model adjusted for age, sex, and energy (kcal/day).

cCox proportional hazards regression model adjusted for variables in Model 1 plus T-stage, number of positive lymph nodes, baseline performance status, treatment arm, BMI (kg/m2), physical activity (MET-h/wk), smoking, aspirin use, and intake of protein (g/day), alcohol (g/day), and fats other than the fat of interest (g/day).

dTotal ω-3 polyunsaturated fats is predominantly alpha-linolenic acid (ALA), but also includes marine ω-3 polyunsaturated fats, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), which we previously reported to be beneficial.(1)

We observed no statistically significant associations between dietary fat and disease-free survival in this prospective study among 1,011 patients with stage III colon cancer. Our team previously reported that a Western dietary pattern and high-glycemic load diets are associated with higher risk of recurrence and death after colon cancer (3, 6), whereas long-chain ω-3 polyunsaturated fatty acids and nuts (rich plant sources of unsaturated fats) are associated with lower risk (1, 2). On the basis of these data, we hypothesized that higher vegetable fat intake would be associated with improved survival, but observed no association. Song and colleagues recently reported that higher fiber intake was associated with lower risk of colorectal cancer mortality in an independent cohort (8). Thus, the beneficial effect of nuts may be related to their low glycemic index and fiber rather than fat content.

Our analysis has many strengths, including large number of events, standardized treatment, and complete follow-up. However, this was an observational study, and therefore, confounding is possible. In addition, there is error in diet assessment, but it is expected to be nondifferential due to our prospective assessment. In conclusion, neither the total amount nor the amount of major types of dietary fat (i.e., saturated, monounsaturated, and polyunsaturated) consumed after colon cancer was associated with disease-free survival.

A. Benson reports receiving commercial research grants from Novartis, Acerta, Xencor, Bristol-Myers Squibb: DMC, Celegene, Advanced Accelerator Applications, Infinity Pharmaceuticas: DMC, Merck Sharp and Dohme, Taiho Pharmaceutical, and Medimmune/AstraZeneca, and is a consultant/advisory board member for Bristol-Myers Squibb, Guardant Health, Axiom, Genentech, Bayer, Merck, Rafael Pharmaceuticals, Astellas DMC, Terumo, Eli Lilly & Company, Exelixis, Purdue Pharma, Harborside, Xcenda, NCCN, Emron, and inVentive Health Inc. No potential conflicts of interest were disclosed by the other authors.

The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.

Conception and design: E.L. Van Blarigan, L. Saltz, E.L. Giovannucci, J.A. Meyerhardt

Development of methodology: C.S. Fuchs

Acquisition of data (provided animals, acquired and managed patients, provided facilities, etc.): S. Zhang, C.S. Fuchs, L. Saltz, R.J. Mayer, S. Ogino, A. Benson, A. Hantel

Analysis and interpretation of data (e.g., statistical analysis, biostatistics, computational analysis): E.L. Van Blarigan, Fang-Shu Ou, D. Niedzwiecki, S. Zhang, C.S. Fuchs, A. Venook, S. Ogino, M. Song, J.A. Meyerhardt

Writing, review, and/or revision of the manuscript: E.L. Van Blarigan, Fang-Shu Ou, D. Niedzwiecki, S. Zhang, L. Saltz, R.J. Mayer, A. Venook, S. Ogino, M. Song, A. Benson, A. Hantel, J.N. Atkins, E.L. Giovannucci, J.A. Meyerhardt

Administrative, technical, or material support (i.e., reporting or organizing data, constructing databases): A. Venook, S. Ogino

Study supervision: C.S. Fuchs, L. Saltz, J.A. Meyerhardt

Research reported in this publication was supported by the NCI of NIH under award numbers U10CA180821 and U10CA180882 (to the Alliance for Clinical Trials in Oncology; D. Niedzwiecki and F. Ou), U10CA138561 (to A.P. Venook), U10CA180791 (to L. Saltz), U10CA180820 (to A. Benson), U10CA180867 (to J.A. Meyerhardt, S. Zhang, R. Mayer, and S. Ogino), U10CA180888 (to A. Hantel), UG1CA189858 (to J.N. Atkins), K07CA197077 (to E.L. Van Blarigan), R01CA118553 (to C.S. Fuchs and D. Niedzwiecki), R01CA149222 (to J.A. Meyerhardt and D. Niedzwiecki), P50CA127003 (to C.S. Fuchs and J.A. Meyerhardt), R35CA197735 (to S. Ogino), and K99CA215314 (to M. Song). Dr. Song also received support from the American Cancer Society (MRSG-17-220-01-NEC) and American Association for Cancer Research (17-40-12-SONG), and this research was supported in part by funds from Pharmacia & Upjohn Company (now Pfizer Oncology; to C. Fuchs). Finally, this research was supported in part by a Stand Up To Cancer Colorectal Cancer Dream Team Translational Research Grant (to C.S. Fuchs, grant number: SU2C-AACR-DT22-17). Research grants are administered by the American Association for Cancer Research, the Scientific Partner of SU2C.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

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