Abstract
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.
Introduction
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.
Materials and Methods
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.
Results
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).
. | Quartile of animal fat . | Quartile of vegetable fat . | ||||
---|---|---|---|---|---|---|
. | 1 . | 4 . | . | 1 . | 4 . | . |
N | 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 | 5 | 10 | 8 | 6 | ||
Other | 6 | 4 | 6 | 4 | ||
Performance status | 0.29 | 0.40 | ||||
Fully active | 76 | 68 | 72 | 73 | ||
Restricted in strenuous activity | 21 | 30 | 27 | 26 | ||
Unknown | 3 | 2 | 1 | 1 | ||
Bowel wall invasion | 0.89 | 0.87 | ||||
T1–T2 | 15 | 14 | 12 | 13 | ||
T3–T4 | 77 | 80 | 83 | 79 | ||
Unknown | 8 | 6 | 5 | 8 | ||
Positive lymph nodes | 0.65 | 0.26 | ||||
1–3 (N1) | 62 | 64 | 67 | 64 | ||
≥4 (N2) | 35 | 34 | 32 | 35 | ||
Unknown | 3 | 2 | 1 | 1 | ||
Clinical bowel abnormality | ||||||
Perforation | 3 | 6 | 0.34 | 3 | 7 | 0.10 |
Obstruction | 23 | 25 | 0.31 | 22 | 23 | 0.32 |
Grade of differentiation | 0.88 | 0.26 | ||||
Well | 4 | 6 | 7 | 6 | ||
Moderate | 71 | 68 | 68 | 72 | ||
Poor | 22 | 24 | 25 | 21 | ||
Unknown | 3 | 2 | 1 | 1 | ||
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 | 6 | 13 | 12 | 10 | ||
Past | 48 | 44 | 44 | 43 | ||
Never | 45 | 42 | 44 | 45 | ||
Unknown | 1 | 1 | 1 | 1 | ||
Aspirin user | 9 | 8 | 0.72 | 7 | 7 | 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 fat . | Quartile of vegetable fat . | ||||
---|---|---|---|---|---|---|
. | 1 . | 4 . | . | 1 . | 4 . | . |
N | 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 | 5 | 10 | 8 | 6 | ||
Other | 6 | 4 | 6 | 4 | ||
Performance status | 0.29 | 0.40 | ||||
Fully active | 76 | 68 | 72 | 73 | ||
Restricted in strenuous activity | 21 | 30 | 27 | 26 | ||
Unknown | 3 | 2 | 1 | 1 | ||
Bowel wall invasion | 0.89 | 0.87 | ||||
T1–T2 | 15 | 14 | 12 | 13 | ||
T3–T4 | 77 | 80 | 83 | 79 | ||
Unknown | 8 | 6 | 5 | 8 | ||
Positive lymph nodes | 0.65 | 0.26 | ||||
1–3 (N1) | 62 | 64 | 67 | 64 | ||
≥4 (N2) | 35 | 34 | 32 | 35 | ||
Unknown | 3 | 2 | 1 | 1 | ||
Clinical bowel abnormality | ||||||
Perforation | 3 | 6 | 0.34 | 3 | 7 | 0.10 |
Obstruction | 23 | 25 | 0.31 | 22 | 23 | 0.32 |
Grade of differentiation | 0.88 | 0.26 | ||||
Well | 4 | 6 | 7 | 6 | ||
Moderate | 71 | 68 | 68 | 72 | ||
Poor | 22 | 24 | 25 | 21 | ||
Unknown | 3 | 2 | 1 | 1 | ||
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 | 6 | 13 | 12 | 10 | ||
Past | 48 | 44 | 44 | 43 | ||
Never | 45 | 42 | 44 | 45 | ||
Unknown | 1 | 1 | 1 | 1 | ||
Aspirin user | 9 | 8 | 0.72 | 7 | 7 | 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.
. | Quartile of intake . | . | |||
---|---|---|---|---|---|
. | 1 . | 2 . | 3 . | 4 . | Ptrenda . |
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 | 9 | 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 . | . | |||
---|---|---|---|---|---|
. | 1 . | 2 . | 3 . | 4 . | Ptrenda . |
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 | 9 | 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)
Discussion
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.
Disclosure of Potential Conflicts of Interest
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.
Disclaimer
The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.
Authors' Contributions
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
Acknowledgments
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.
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