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 - 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 -