PT - JOURNAL ARTICLE AU - Kosuke Mima AU - Reiko Nishihara AU - Zhi Rong Qian AU - Yin Cao AU - Yasutaka Sukawa AU - Jonathan A Nowak AU - Juhong Yang AU - Ruoxu Dou AU - Yohei Masugi AU - Mingyang Song AU - Aleksandar D Kostic AU - Marios Giannakis AU - Susan Bullman AU - Danny A Milner AU - Hideo Baba AU - Edward L Giovannucci AU - Levi A Garraway AU - Gordon J Freeman AU - Glenn Dranoff AU - Wendy S Garrett AU - Curtis Huttenhower AU - Matthew Meyerson AU - Jeffrey A Meyerhardt AU - Andrew T Chan AU - Charles S Fuchs AU - Shuji Ogino TI - <em>Fusobacterium nucleatum</em> in colorectal carcinoma tissue and patient prognosis AID - 10.1136/gutjnl-2015-310101 DP - 2016 Dec 01 TA - Gut PG - 1973--1980 VI - 65 IP - 12 4099 - http://gut.bmj.com/content/65/12/1973.short 4100 - http://gut.bmj.com/content/65/12/1973.full SO - Gut2016 Dec 01; 65 AB - Objective Accumulating evidence links the intestinal microbiota and colorectal carcinogenesis. Fusobacterium nucleatum may promote colorectal tumour growth and inhibit T cell-mediated immune responses against colorectal tumours. Thus, we hypothesised that the amount of F. nucleatum in colorectal carcinoma might be associated with worse clinical outcome.Design We used molecular pathological epidemiology database of 1069 rectal and colon cancer cases in the Nurses’ Health Study and the Health Professionals Follow-up Study, and measured F. nucleatum DNA in carcinoma tissue. Cox proportional hazards model was used to compute hazard ratio (HR), controlling for potential confounders, including microsatellite instability (MSI, mismatch repair deficiency), CpG island methylator phenotype (CIMP), KRAS, BRAF, and PIK3CA mutations, and LINE-1 hypomethylation (low-level methylation).Results Compared with F. nucleatum-negative cases, multivariable HRs (95% CI) for colorectal cancer-specific mortality in F. nucleatum-low cases and F. nucleatum-high cases were 1.25 (0.82 to 1.92) and 1.58 (1.04 to 2.39), respectively, (p for trend=0.020). The amount of F. nucleatum was associated with MSI-high (multivariable odd ratio (OR), 5.22; 95% CI 2.86 to 9.55) independent of CIMP and BRAF mutation status, whereas CIMP and BRAF mutation were associated with F. nucleatum only in univariate analyses (p&lt;0.001) but not in multivariate analysis that adjusted for MSI status.Conclusions The amount of F. nucleatum DNA in colorectal cancer tissue is associated with shorter survival, and may potentially serve as a prognostic biomarker. Our data may have implications in developing cancer prevention and treatment strategies through targeting GI microflora by diet, probiotics and antibiotics.