Affiliation:
1. Department of Pathology and Clinical Bioinformatics, The Tumor Immuno‐Pathology Laboratory Erasmus University Medical Center Rotterdam the Netherlands
2. Department of Epidemiology Erasmus University Medical Center Rotterdam the Netherlands
3. Department of Internal Medicine Erasmus University Medical Center Rotterdam the Netherlands
4. Department of Human Genetics, Laboratory for Systems Medicine Center for Human Genetics, KU Leuven Leuven Belgium
5. Department of Surgery Erasmus University Medical Center Rotterdam the Netherlands
Abstract
AbstractThe immune response–gut microbiota interaction is implicated in various human diseases, including cancer. Identifying the link between the gut microbiota and systemic inflammatory markers and their association with cancer will be important for our understanding of cancer etiology. The current study was performed on 8090 participants from the population‐based Rotterdam study. We found a significant association (false discovery rate [FDR] ≤0.05) between lymphocytes and three gut microbial taxa, namely the family Streptococcaceae, genus Streptococcus, and order Lactobacillales. In addition, we identified 95 gut microbial taxa that were associated with inflammatory markers (p < 0.05). Analyzing the cancer data, we observed a significant association between higher systemic immune‐inflammation index (SII) levels at baseline (hazard ratio (HR): 1.65 [95% confidence interval (CI); 1.10–2.46, p ≤ 0.05]) and a higher count of lymphocytes (HR: 1.38 [95% CI: 1.15–1.65, p ≤ 0.05]) and granulocytes (HR: 1.69 [95% CI: 1.40–2.03, p ≤ 0.05]) with increased risk of lung cancer after adjusting for age, sex, body mass index (BMI), and study cohort. This association was lost for SII and lymphocytes after additional adjustment for smoking (SII = HR:1.46 [95% CI: 0.96–2.22, p = 0.07] and lymphocytes = HR: 1.19 [95% CI: 0.97–1.46, p = 0.08]). In the stratified analysis, higher count of lymphocyte and granulocytes at baseline were associated with an increased risk of lung cancer in smokers after adjusting for age, sex, BMI, and study cohort (HR: 1.33 [95% CI: 1.09–1.62, p ≤0.05] and HR: 1.57 [95% CI: 1.28–1.92, p ≤0.05], respectively). Our study revealed a positive association between gut microbiota, higher SII levels, and higher lymphocyte and granulocyte counts, with an increased risk of developing lung cancer.
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