Marine omega-3 fatty acid intake and survival of stage III colon cancer according to tumor molecular markers in NCCTG Phase III trial N0147 (Alliance)

Mingyang Song, Fang-Shu Ou, Tyler J. Zemla, Mark A. Hull, Qian D Shi, Paul John Limburg, Steven Robert Alberts, Frank A Sinicrope, Edward L. Giovannucci, Erin L. Van Blarigan, Jeffrey A. Meyerhardt, Andrew T. Chan

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Marine omega-3 polyunsaturated fatty acids (MO3PUFAs) have anticancer properties and may improve colon cancer survival. However, it remains unknown whether the benefit differs by tumor molecular subtype. We examined data from a phase III randomized trial of FOLFOX or FOLFOX + cetuximab among 1,735 stage III colon cancer patients who completed a dietary questionnaire at enrollment. Multivariable hazard ratios and 95% confidence intervals (CIs) were calculated for the association between MO3PUFA and disease-free survival (DFS) and overall survival according to KRAS and BRAFV600E mutations and DNA mismatch repair (MMR) status. Higher MO3PUFA intake was associated with improved 3-year DFS for KRAS wild-type tumors (77% vs. 73%; HR: 0.84; 95% CI: 0.67–1.05) but not KRAS-mutant tumors (64% vs. 70%; HR: 1.30; 95% CI: 0.97–1.73; Pinteraction = 0.02). Similar heterogeneity was found by MMR (Pinteraction = 0.14): higher MO3PUFA was associated with better 3-year DFS for tumors with deficient MMR (72% vs. 67%) but not proficient MMR (72% vs. 72%). No heterogeneity was found by BRAFV600E mutation. Similar findings were obtained for overall survival. In conclusion, we found a suggestive beneficial association between higher MO3PUFA intake and improved survival among stage III colon cancer patients with wild-type KRAS and deficient MMR. Given the relatively small number of cases with tumor molecular assessments, further studies, preferably through pooled analyses of multiples cohorts, are needed to validate our findings.

Original languageEnglish (US)
JournalInternational Journal of Cancer
DOIs
StateAccepted/In press - Jan 1 2019

Fingerprint

DNA Mismatch Repair
Omega-3 Fatty Acids
Tumor Biomarkers
Unsaturated Fatty Acids
Colonic Neoplasms
Survival
Disease-Free Survival
Confidence Intervals
Neoplasms
Mutation
Cohort Studies

Keywords

  • colorectal cancer
  • inflammation
  • nutrition
  • survivorship care
  • tumor microenvironment

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Marine omega-3 fatty acid intake and survival of stage III colon cancer according to tumor molecular markers in NCCTG Phase III trial N0147 (Alliance). / Song, Mingyang; Ou, Fang-Shu; Zemla, Tyler J.; Hull, Mark A.; Shi, Qian D; Limburg, Paul John; Alberts, Steven Robert; Sinicrope, Frank A; Giovannucci, Edward L.; Van Blarigan, Erin L.; Meyerhardt, Jeffrey A.; Chan, Andrew T.

In: International Journal of Cancer, 01.01.2019.

Research output: Contribution to journalArticle

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title = "Marine omega-3 fatty acid intake and survival of stage III colon cancer according to tumor molecular markers in NCCTG Phase III trial N0147 (Alliance)",
abstract = "Marine omega-3 polyunsaturated fatty acids (MO3PUFAs) have anticancer properties and may improve colon cancer survival. However, it remains unknown whether the benefit differs by tumor molecular subtype. We examined data from a phase III randomized trial of FOLFOX or FOLFOX + cetuximab among 1,735 stage III colon cancer patients who completed a dietary questionnaire at enrollment. Multivariable hazard ratios and 95{\%} confidence intervals (CIs) were calculated for the association between MO3PUFA and disease-free survival (DFS) and overall survival according to KRAS and BRAFV600E mutations and DNA mismatch repair (MMR) status. Higher MO3PUFA intake was associated with improved 3-year DFS for KRAS wild-type tumors (77{\%} vs. 73{\%}; HR: 0.84; 95{\%} CI: 0.67–1.05) but not KRAS-mutant tumors (64{\%} vs. 70{\%}; HR: 1.30; 95{\%} CI: 0.97–1.73; Pinteraction = 0.02). Similar heterogeneity was found by MMR (Pinteraction = 0.14): higher MO3PUFA was associated with better 3-year DFS for tumors with deficient MMR (72{\%} vs. 67{\%}) but not proficient MMR (72{\%} vs. 72{\%}). No heterogeneity was found by BRAFV600E mutation. Similar findings were obtained for overall survival. In conclusion, we found a suggestive beneficial association between higher MO3PUFA intake and improved survival among stage III colon cancer patients with wild-type KRAS and deficient MMR. Given the relatively small number of cases with tumor molecular assessments, further studies, preferably through pooled analyses of multiples cohorts, are needed to validate our findings.",
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author = "Mingyang Song and Fang-Shu Ou and Zemla, {Tyler J.} and Hull, {Mark A.} and Shi, {Qian D} and Limburg, {Paul John} and Alberts, {Steven Robert} and Sinicrope, {Frank A} and Giovannucci, {Edward L.} and {Van Blarigan}, {Erin L.} and Meyerhardt, {Jeffrey A.} and Chan, {Andrew T.}",
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AU - Song, Mingyang

AU - Ou, Fang-Shu

AU - Zemla, Tyler J.

AU - Hull, Mark A.

AU - Shi, Qian D

AU - Limburg, Paul John

AU - Alberts, Steven Robert

AU - Sinicrope, Frank A

AU - Giovannucci, Edward L.

AU - Van Blarigan, Erin L.

AU - Meyerhardt, Jeffrey A.

AU - Chan, Andrew T.

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AB - Marine omega-3 polyunsaturated fatty acids (MO3PUFAs) have anticancer properties and may improve colon cancer survival. However, it remains unknown whether the benefit differs by tumor molecular subtype. We examined data from a phase III randomized trial of FOLFOX or FOLFOX + cetuximab among 1,735 stage III colon cancer patients who completed a dietary questionnaire at enrollment. Multivariable hazard ratios and 95% confidence intervals (CIs) were calculated for the association between MO3PUFA and disease-free survival (DFS) and overall survival according to KRAS and BRAFV600E mutations and DNA mismatch repair (MMR) status. Higher MO3PUFA intake was associated with improved 3-year DFS for KRAS wild-type tumors (77% vs. 73%; HR: 0.84; 95% CI: 0.67–1.05) but not KRAS-mutant tumors (64% vs. 70%; HR: 1.30; 95% CI: 0.97–1.73; Pinteraction = 0.02). Similar heterogeneity was found by MMR (Pinteraction = 0.14): higher MO3PUFA was associated with better 3-year DFS for tumors with deficient MMR (72% vs. 67%) but not proficient MMR (72% vs. 72%). No heterogeneity was found by BRAFV600E mutation. Similar findings were obtained for overall survival. In conclusion, we found a suggestive beneficial association between higher MO3PUFA intake and improved survival among stage III colon cancer patients with wild-type KRAS and deficient MMR. Given the relatively small number of cases with tumor molecular assessments, further studies, preferably through pooled analyses of multiples cohorts, are needed to validate our findings.

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