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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)
Author(s) -
Song Mingyang,
Ou FangShu,
Zemla Tyler J.,
Hull Mark A.,
Shi Qian,
Limburg Paul J.,
Alberts Steven R.,
Sinicrope Frank A.,
Giovannucci Edward L.,
Van Blarigan Erin L.,
Meyerhardt Jeffrey A.,
Chan Andrew T.
Publication year - 2019
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.32113
Subject(s) - medicine , folfox , kras , colorectal cancer , hazard ratio , oncology , stage (stratigraphy) , cetuximab , cancer , confidence interval , gastroenterology , oxaliplatin , biology , paleontology
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 BRAF V600E 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; P interaction = 0.02). Similar heterogeneity was found by MMR ( P interaction = 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 BRAF V600E 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.