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.

• Authors: Mingyang Song, Fang-Shu Ou, Tyler J Zemla, Mark A Hull, Qian Shi, Paul J Limburg, Steven R Alberts, Frank A Sinicrope, Edward L Giovannucci, Erin L Van Blarigan, Jeffrey A Meyerhardt, Andrew T Chan
• Journal: International journal of cancer (Int J Cancer) Vol. 145 Issue 2 Pg. 380-389 (07 15 2019) ISSN: 1097-0215 [Electronic] United States
• PMID: 30623420 (Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: © 2019 UICC.

Chemical References

• Fatty Acids, Omega-3
• Fish Oils
• KRAS protein, human
• BRAF protein, human
• Proto-Oncogene Proteins B-raf
• Proto-Oncogene Proteins p21(ras)
• Cetuximab
• Fluorouracil

Topics

• Aged
• Cetuximab (therapeutic use)
• Colonic Neoplasms (diet therapy, drug therapy, genetics)
• Disease-Free Survival
• Fatty Acids, Omega-3 (administration & dosage)
• Female
• Fish Oils (administration & dosage)
• Fluorouracil (therapeutic use)
• Humans
• Male
• Microsatellite Instability
• Middle Aged
• Neoplasm Staging
• Proto-Oncogene Proteins B-raf (genetics)
• Proto-Oncogene Proteins p21(ras) (genetics)
• Treatment Outcome