Circulating markers of microbial translocation and host response to bacteria with risk of colorectal cancer: a prospective, nested case-control study in men

被引：13

作者：

Shi, Mengyao ^{[1
]}

Zong, Xiaoyu ^{[1
]}

Hur, Jinhee ^{[2
,3
,4
]}

Birmann, Brenda M. ^{[5
,6
]}

Martinez-Maza, Otoniel ^{[7
,8
,9
]}

Epeldegui, Marta ^{[9
]}

Chan, Andrew T. ^{[6
,10
,11
,12
,13
]}

Giovannucci, Edward L. ^{[2
,14
]}

Cao, Yin ^{[1
,15
,16
]}

机构：

[1] Washington Univ, Sch Med, Dept Surg, Div Publ Hlth Sci, 660 S Euclid Ave,Campus Box 8100, St Louis, MO 63110 USA

[2] Harvard TH Chan Sch Publ Hlth, Dept Nutr, Boston, MA USA

[3] Sungkyunkwan Univ, Dept Food Sci & Biotechnol, Suwon, Gyeonggi, South Korea

[4] Sungkyunkwan Univ, Inst Biotechnol & Bioengn, Food Clin Res Ctr, Suwon, Gyeonggi, South Korea

[5] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA

[6] Harvard Med Sch, Boston, MA 02115 USA

[7] Univ Calif Los Angeles, David Geffen Sch Med, Dept Obstet & Gynecol, AIDS Inst, Los Angeles, CA 90095 USA

[8] Univ Calif Los Angeles, Fielding Sch Publ Hlth, Dept Epidemiol, Los Angeles, CA USA

[9] Univ Calif Los Angeles, David Geffen Sch Med, Dept Microbiol Immunol & Mol Genet, Los Angeles, CA 90095 USA

[10] Massachusetts Gen Hosp, Dept Med, Clin & Translat Epidemiol Unit, Boston, MA 02114 USA

[11] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA

[12] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA

[13] Harvard TH Chan Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA USA

[14] Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA

[15] Washington Univ, Sch Med, Dept Med, Div Gastroenterol, St Louis, MO 63110 USA

[16] Washington Univ, Sch Med, Alvin J Siteman Canc Ctr, St Louis, MO USA

来源：

EBIOMEDICINE | 2023年 / 91卷

基金：

美国国家卫生研究院;

关键词：

Colorectal cancer; Microbial translocation; Gut dysbiosis; STANDARDIZED REGRESSION-COEFFICIENTS; POLYMORPHISMS; STATISTICS; BIOMARKERS; RECEPTORS; GENE; CD14;

D O I：

10.1016/j.ebiom.2023.104566

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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 trans-location 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 menin 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.

引用

页数：10