TY - JOUR
T1 - Circulating markers of microbial translocation and host response to bacteria with risk of colorectal cancer
T2 - a prospective, nested case-control study in men
AU - Shi, Mengyao
AU - Zong, Xiaoyu
AU - Hur, Jinhee
AU - Birmann, Brenda M.
AU - Martinez-Maza, Otoniel
AU - Epeldegui, Marta
AU - Chan, Andrew T.
AU - Giovannucci, Edward L.
AU - Cao, Yin
N1 - Funding Information:
Funding/Support: This work was supported by grants U01 CA167552 , R01 CA202704 (ATC), R35 CA253185 (ATC), R21 AA027608 (YC), and R37 CA246175 (YC) from the National Institutes of Health . The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. ATC is supported as an American Cancer Society Clinical Research Professor and a Massachusetts General Hospital Stuart and Suzanne Steele Research Scholars Award.
Funding Information:
The authors would like to acknowledge the contribution to this study from central cancer registries supported through the Centers for Disease Control and Prevention's National Program of Cancer Registries (NPCR) and/or the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) Program. Central registries may also be supported by state agencies, universities, and cancer centers. Participating central cancer registries include the following: Alabama, Alaska, Arizona, Arkansas, California, Colorado, Connecticut, Delaware, Florida, Georgia, Hawaii, Idaho, Indiana, Iowa, Kentucky, Louisiana, Massachusetts, Maine, Maryland, Michigan, Mississippi, Montana, Nebraska, Nevada, New Hampshire, New Jersey, New Mexico, New York, North Carolina, North Dakota, Ohio, Oklahoma, Oregon, Pennsylvania, Puerto Rico, Rhode Island, Seattle SEER Registry, South Carolina, Tennessee, Texas, Utah, Virginia, West Virginia, Wyoming.
Funding Information:
US National Institutes of Health.The authors would like to acknowledge the contribution to this study from central cancer registries supported through the Centers for Disease Control and Prevention's National Program of Cancer Registries (NPCR) and/or the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) Program. Central registries may also be supported by state agencies, universities, and cancer centers. Participating central cancer registries include the following: Alabama, Alaska, Arizona, Arkansas, California, Colorado, Connecticut, Delaware, Florida, Georgia, Hawaii, Idaho, Indiana, Iowa, Kentucky, Louisiana, Massachusetts, Maine, Maryland, Michigan, Mississippi, Montana, Nebraska, Nevada, New Hampshire, New Jersey, New Mexico, New York, North Carolina, North Dakota, Ohio, Oklahoma, Oregon, Pennsylvania, Puerto Rico, Rhode Island, Seattle SEER Registry, South Carolina, Tennessee, Texas, Utah, Virginia, West Virginia, Wyoming. Funding/Support: This work was supported by grants U01 CA167552, R01 CA202704 (ATC), R35 CA253185 (ATC), R21 AA027608 (YC), and R37 CA246175 (YC) from the National Institutes of Health. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. ATC is supported as an American Cancer Society Clinical Research Professor and a Massachusetts General Hospital Stuart and Suzanne Steele Research Scholars Award.
Publisher Copyright:
© 2023 The Author(s)
PY - 2023/5
Y1 - 2023/5
N2 - Background: Gut microbial dysbiosis contributes to colorectal cancer (CRC) pathogenesis, possibly mediated in part by increased intestinal permeability to endotoxin lipopolysaccharide (LPS), microbial translocation, and subsequent endotoxemia and inflammation. However, epidemiologic evidence linking circulating markers of microbial translocation with CRC risk is limited. Methods: We conducted a prospective, nested case–control study of 261 incident CRC cases and 261 controls (matched on age and time of blood draw) among 18,159 men with pre-diagnostic blood specimens in the Health Professionals Follow-Up Study (1993–2009). We examined three complementary markers of microbial translocation and host response to bacteria, including LPS-binding protein (LBP), soluble CD14 (sCD14), and endotoxincore antibody (EndoCAb) immunoglobulin M (IgM), with subsequent risk of CRC. Unconditional logistic regressions were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Findings: Pre-diagnostic circulating levels of sCD14 were associated with a higher risk of incident CRC. Compared to men in the lowest quartile, the multivariable OR was 1.90 (95% CI, 1.13–3.22) for men in the highest quartile (OR per standard deviation [SD] increase, 1.28; 95%CI 1.06–1.53; Ptrend = 0.01). This positive association remained similar after adjusting for C-reactive protein, interleukin-6, and soluble tumor necrosis factor receptor-2, and within strata of putative CRC risk factors. We also observed a suggestive inverse association between EndoCAb IgM and risk of CRC (OR per SD increase, 0.84; 95%CI 0.69–1.02; Ptrend = 0.09). Interpretation: Microbial translocation and host response to bacteria, as reflected by sCD14, is associated with risk of incident CRC in men. Funding: US National Institutes of Health.
AB - Background: Gut microbial dysbiosis contributes to colorectal cancer (CRC) pathogenesis, possibly mediated in part by increased intestinal permeability to endotoxin lipopolysaccharide (LPS), microbial translocation, and subsequent endotoxemia and inflammation. However, epidemiologic evidence linking circulating markers of microbial translocation with CRC risk is limited. Methods: We conducted a prospective, nested case–control study of 261 incident CRC cases and 261 controls (matched on age and time of blood draw) among 18,159 men with pre-diagnostic blood specimens in the Health Professionals Follow-Up Study (1993–2009). We examined three complementary markers of microbial translocation and host response to bacteria, including LPS-binding protein (LBP), soluble CD14 (sCD14), and endotoxincore antibody (EndoCAb) immunoglobulin M (IgM), with subsequent risk of CRC. Unconditional logistic regressions were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Findings: Pre-diagnostic circulating levels of sCD14 were associated with a higher risk of incident CRC. Compared to men in the lowest quartile, the multivariable OR was 1.90 (95% CI, 1.13–3.22) for men in the highest quartile (OR per standard deviation [SD] increase, 1.28; 95%CI 1.06–1.53; Ptrend = 0.01). This positive association remained similar after adjusting for C-reactive protein, interleukin-6, and soluble tumor necrosis factor receptor-2, and within strata of putative CRC risk factors. We also observed a suggestive inverse association between EndoCAb IgM and risk of CRC (OR per SD increase, 0.84; 95%CI 0.69–1.02; Ptrend = 0.09). Interpretation: Microbial translocation and host response to bacteria, as reflected by sCD14, is associated with risk of incident CRC in men. Funding: US National Institutes of Health.
KW - Colorectal cancer
KW - Gut dysbiosis
KW - Microbial translocation
UR - http://www.scopus.com/inward/record.url?scp=85152532544&partnerID=8YFLogxK
U2 - 10.1016/j.ebiom.2023.104566
DO - 10.1016/j.ebiom.2023.104566
M3 - Article
C2 - 37075493
AN - SCOPUS:85152532544
SN - 2352-3964
VL - 91
JO - EBioMedicine
JF - EBioMedicine
M1 - 104566
ER -