Fusobacterium nucleatum in Colorectal Carcinoma Tissue According to Tumor Location

Kosuke Mima, Yin Cao, Andrew T. Chan, Zhi Rong Qian, Jonathan A. Nowak, Yohei Masugi, Yan Shi, Mingyang Song, Annacarolina Da Silva, Mancang Gu, Wanwan Li, Tsuyoshi Hamada, Keisuke Kosumi, Akiko Hanyuda, Li Liu, Aleksandar D. Kostic, Marios Giannakis, Susan Bullman, Caitlin A. Brennan, Danny A. MilnerHideo Baba, Levi A. Garraway, Jeffrey A. Meyerhardt, Wendy S. Garrett, Curtis Huttenhower, Matthew Meyerson, Edward L. Giovannucci, Charles S. Fuchs, Reiko Nishihara, Shuji Ogino

Research output: Contribution to journalArticle

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Abstract

Objectives:Evidence suggests a possible role of Fusobacterium nucleatum in colorectal carcinogenesis, especially in right-sided proximal colorectum. Considering a change in bowel contents and microbiome from proximal to distal colorectal segments, we hypothesized that the proportion of colorectal carcinoma enriched with F. nucleatum might gradually increase along the bowel subsites from rectum to cecum.Methods:A retrospective, cross-sectional analysis was conducted on 1,102 colon and rectal carcinomas in molecular pathological epidemiology databases of the Nurses' Health Study and the Health Professionals Follow-up Study. We measured the amount of F. nucleatum DNA in colorectal tumor tissue using a quantitative PCR assay and equally dichotomized F. nucleatum-positive cases (high vs. low). We used multivariable logistic regression analysis to examine the relationship of a bowel subsite variable (rectum, rectosigmoid junction, sigmoid colon, descending colon, splenic flexure, transverse colon, hepatic flexure, ascending colon, and cecum) with the amount of F. nucleatum.Results:The proportion of F. nucleatum-high colorectal cancers gradually increased from rectal cancers (2.5%; 4/157) to cecal cancers (11%; 19/178), with a statistically significant linear trend along all subsites (P<0.0001) and little evidence of non-linearity. The proportion of F. nucleatum-low cancers was higher in rectal, ascending colon, and cecal cancers than in cancers of middle segments.Conclusions:The proportion of F. nucleatum-high colorectal cancers gradually increases from rectum to cecum. Our data support the colorectal continuum model that reflects pathogenic influences of the gut microbiota on neoplastic and immune cells and challenges the prevailing two-colon (proximal vs. distal) dichotomy paradigm.

Original languageEnglish
Article numbere200
JournalClinical and Translational Gastroenterology
Volume7
Issue number11
DOIs
Publication statusPublished - 2016 Nov 3
Externally publishedYes

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Fusobacterium nucleatum
Colorectal Neoplasms
Cecum
Neoplasms
Cecal Neoplasms
Rectum
Ascending Colon
Transverse Colon
Colon
Descending Colon
Molecular Epidemiology
Microbiota
Health
Sigmoid Colon
Rectal Neoplasms
Colonic Neoplasms
Carcinogenesis
Cross-Sectional Studies
Logistic Models
Nurses

ASJC Scopus subject areas

  • Gastroenterology

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Fusobacterium nucleatum in Colorectal Carcinoma Tissue According to Tumor Location. / Mima, Kosuke; Cao, Yin; Chan, Andrew T.; Qian, Zhi Rong; Nowak, Jonathan A.; Masugi, Yohei; Shi, Yan; Song, Mingyang; Da Silva, Annacarolina; Gu, Mancang; Li, Wanwan; Hamada, Tsuyoshi; Kosumi, Keisuke; Hanyuda, Akiko; Liu, Li; Kostic, Aleksandar D.; Giannakis, Marios; Bullman, Susan; Brennan, Caitlin A.; Milner, Danny A.; Baba, Hideo; Garraway, Levi A.; Meyerhardt, Jeffrey A.; Garrett, Wendy S.; Huttenhower, Curtis; Meyerson, Matthew; Giovannucci, Edward L.; Fuchs, Charles S.; Nishihara, Reiko; Ogino, Shuji.

In: Clinical and Translational Gastroenterology, Vol. 7, No. 11, e200, 03.11.2016.

Research output: Contribution to journalArticle

Mima, K, Cao, Y, Chan, AT, Qian, ZR, Nowak, JA, Masugi, Y, Shi, Y, Song, M, Da Silva, A, Gu, M, Li, W, Hamada, T, Kosumi, K, Hanyuda, A, Liu, L, Kostic, AD, Giannakis, M, Bullman, S, Brennan, CA, Milner, DA, Baba, H, Garraway, LA, Meyerhardt, JA, Garrett, WS, Huttenhower, C, Meyerson, M, Giovannucci, EL, Fuchs, CS, Nishihara, R & Ogino, S 2016, 'Fusobacterium nucleatum in Colorectal Carcinoma Tissue According to Tumor Location', Clinical and Translational Gastroenterology, vol. 7, no. 11, e200. https://doi.org/10.1038/ctg.2016.53
Mima, Kosuke ; Cao, Yin ; Chan, Andrew T. ; Qian, Zhi Rong ; Nowak, Jonathan A. ; Masugi, Yohei ; Shi, Yan ; Song, Mingyang ; Da Silva, Annacarolina ; Gu, Mancang ; Li, Wanwan ; Hamada, Tsuyoshi ; Kosumi, Keisuke ; Hanyuda, Akiko ; Liu, Li ; Kostic, Aleksandar D. ; Giannakis, Marios ; Bullman, Susan ; Brennan, Caitlin A. ; Milner, Danny A. ; Baba, Hideo ; Garraway, Levi A. ; Meyerhardt, Jeffrey A. ; Garrett, Wendy S. ; Huttenhower, Curtis ; Meyerson, Matthew ; Giovannucci, Edward L. ; Fuchs, Charles S. ; Nishihara, Reiko ; Ogino, Shuji. / Fusobacterium nucleatum in Colorectal Carcinoma Tissue According to Tumor Location. In: Clinical and Translational Gastroenterology. 2016 ; Vol. 7, No. 11.
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abstract = "Objectives:Evidence suggests a possible role of Fusobacterium nucleatum in colorectal carcinogenesis, especially in right-sided proximal colorectum. Considering a change in bowel contents and microbiome from proximal to distal colorectal segments, we hypothesized that the proportion of colorectal carcinoma enriched with F. nucleatum might gradually increase along the bowel subsites from rectum to cecum.Methods:A retrospective, cross-sectional analysis was conducted on 1,102 colon and rectal carcinomas in molecular pathological epidemiology databases of the Nurses' Health Study and the Health Professionals Follow-up Study. We measured the amount of F. nucleatum DNA in colorectal tumor tissue using a quantitative PCR assay and equally dichotomized F. nucleatum-positive cases (high vs. low). We used multivariable logistic regression analysis to examine the relationship of a bowel subsite variable (rectum, rectosigmoid junction, sigmoid colon, descending colon, splenic flexure, transverse colon, hepatic flexure, ascending colon, and cecum) with the amount of F. nucleatum.Results:The proportion of F. nucleatum-high colorectal cancers gradually increased from rectal cancers (2.5{\%}; 4/157) to cecal cancers (11{\%}; 19/178), with a statistically significant linear trend along all subsites (P<0.0001) and little evidence of non-linearity. The proportion of F. nucleatum-low cancers was higher in rectal, ascending colon, and cecal cancers than in cancers of middle segments.Conclusions:The proportion of F. nucleatum-high colorectal cancers gradually increases from rectum to cecum. Our data support the colorectal continuum model that reflects pathogenic influences of the gut microbiota on neoplastic and immune cells and challenges the prevailing two-colon (proximal vs. distal) dichotomy paradigm.",
author = "Kosuke Mima and Yin Cao and Chan, {Andrew T.} and Qian, {Zhi Rong} and Nowak, {Jonathan A.} and Yohei Masugi and Yan Shi and Mingyang Song and {Da Silva}, Annacarolina and Mancang Gu and Wanwan Li and Tsuyoshi Hamada and Keisuke Kosumi and Akiko Hanyuda and Li Liu and Kostic, {Aleksandar D.} and Marios Giannakis and Susan Bullman and Brennan, {Caitlin A.} and Milner, {Danny A.} and Hideo Baba and Garraway, {Levi A.} and Meyerhardt, {Jeffrey A.} and Garrett, {Wendy S.} and Curtis Huttenhower and Matthew Meyerson and Giovannucci, {Edward L.} and Fuchs, {Charles S.} and Reiko Nishihara and Shuji Ogino",
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T1 - Fusobacterium nucleatum in Colorectal Carcinoma Tissue According to Tumor Location

AU - Mima, Kosuke

AU - Cao, Yin

AU - Chan, Andrew T.

AU - Qian, Zhi Rong

AU - Nowak, Jonathan A.

AU - Masugi, Yohei

AU - Shi, Yan

AU - Song, Mingyang

AU - Da Silva, Annacarolina

AU - Gu, Mancang

AU - Li, Wanwan

AU - Hamada, Tsuyoshi

AU - Kosumi, Keisuke

AU - Hanyuda, Akiko

AU - Liu, Li

AU - Kostic, Aleksandar D.

AU - Giannakis, Marios

AU - Bullman, Susan

AU - Brennan, Caitlin A.

AU - Milner, Danny A.

AU - Baba, Hideo

AU - Garraway, Levi A.

AU - Meyerhardt, Jeffrey A.

AU - Garrett, Wendy S.

AU - Huttenhower, Curtis

AU - Meyerson, Matthew

AU - Giovannucci, Edward L.

AU - Fuchs, Charles S.

AU - Nishihara, Reiko

AU - Ogino, Shuji

PY - 2016/11/3

Y1 - 2016/11/3

N2 - Objectives:Evidence suggests a possible role of Fusobacterium nucleatum in colorectal carcinogenesis, especially in right-sided proximal colorectum. Considering a change in bowel contents and microbiome from proximal to distal colorectal segments, we hypothesized that the proportion of colorectal carcinoma enriched with F. nucleatum might gradually increase along the bowel subsites from rectum to cecum.Methods:A retrospective, cross-sectional analysis was conducted on 1,102 colon and rectal carcinomas in molecular pathological epidemiology databases of the Nurses' Health Study and the Health Professionals Follow-up Study. We measured the amount of F. nucleatum DNA in colorectal tumor tissue using a quantitative PCR assay and equally dichotomized F. nucleatum-positive cases (high vs. low). We used multivariable logistic regression analysis to examine the relationship of a bowel subsite variable (rectum, rectosigmoid junction, sigmoid colon, descending colon, splenic flexure, transverse colon, hepatic flexure, ascending colon, and cecum) with the amount of F. nucleatum.Results:The proportion of F. nucleatum-high colorectal cancers gradually increased from rectal cancers (2.5%; 4/157) to cecal cancers (11%; 19/178), with a statistically significant linear trend along all subsites (P<0.0001) and little evidence of non-linearity. The proportion of F. nucleatum-low cancers was higher in rectal, ascending colon, and cecal cancers than in cancers of middle segments.Conclusions:The proportion of F. nucleatum-high colorectal cancers gradually increases from rectum to cecum. Our data support the colorectal continuum model that reflects pathogenic influences of the gut microbiota on neoplastic and immune cells and challenges the prevailing two-colon (proximal vs. distal) dichotomy paradigm.

AB - Objectives:Evidence suggests a possible role of Fusobacterium nucleatum in colorectal carcinogenesis, especially in right-sided proximal colorectum. Considering a change in bowel contents and microbiome from proximal to distal colorectal segments, we hypothesized that the proportion of colorectal carcinoma enriched with F. nucleatum might gradually increase along the bowel subsites from rectum to cecum.Methods:A retrospective, cross-sectional analysis was conducted on 1,102 colon and rectal carcinomas in molecular pathological epidemiology databases of the Nurses' Health Study and the Health Professionals Follow-up Study. We measured the amount of F. nucleatum DNA in colorectal tumor tissue using a quantitative PCR assay and equally dichotomized F. nucleatum-positive cases (high vs. low). We used multivariable logistic regression analysis to examine the relationship of a bowel subsite variable (rectum, rectosigmoid junction, sigmoid colon, descending colon, splenic flexure, transverse colon, hepatic flexure, ascending colon, and cecum) with the amount of F. nucleatum.Results:The proportion of F. nucleatum-high colorectal cancers gradually increased from rectal cancers (2.5%; 4/157) to cecal cancers (11%; 19/178), with a statistically significant linear trend along all subsites (P<0.0001) and little evidence of non-linearity. The proportion of F. nucleatum-low cancers was higher in rectal, ascending colon, and cecal cancers than in cancers of middle segments.Conclusions:The proportion of F. nucleatum-high colorectal cancers gradually increases from rectum to cecum. Our data support the colorectal continuum model that reflects pathogenic influences of the gut microbiota on neoplastic and immune cells and challenges the prevailing two-colon (proximal vs. distal) dichotomy paradigm.

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