Bethany Van Guelpen

Background: Antibiotics use is associated with higher colorectal cancer risk, but little is known regarding any potential effects on survival. Methods: We conducted a nationwide cohort study, using complete-population data from Swedish national registers between 2005 and 2020, to investigate prediagnostic prescription antibiotics use in relation to survival in colorectal cancer patients. Results: We identified 36,061 stage I–III and 11,242 stage IV colorectal cancer cases diagnosed between 2010 and 2019. For stage I–III, any antibiotics use (binary yes/no variable) was not associated with overall or cancer-specific survival. Compared with no use, moderate antibiotics use (total 11–60 days) was associated with slightly better cancer-specific survival [adjusted HR (aHR) = 0.93; 95% confidence interval (CI), 0.86–0.99)], whereas very high use (>180 days) was associated with worse survival [overall survival (OS) aHR = 1.42; 95% CI, 1.26–1.60, cancer-specific survival aHR = 1.31; 95% CI, 1.10–1.55]. In analyses by different antibiotic types, although not statistically significant, worse survival outcomes were generally observed across several antibiotics, particularly macrolides and/or lincosamides. In stage IV colorectal cancer, inverse relationships between antibiotics use and survival were noted. Conclusions: Overall, our findings do not support any substantial detrimental effects of prediagnostic prescription antibiotics use on cancer-specific survival after colorectal cancer diagnosis, with the possible exception of very high use in stage I–III colorectal cancer. Further investigation is warranted to confirm and understand these results. Impact: Although the study findings require confirmation, physicians probably do not need to factor in prediagnostic prescription antibiotics use in prognosticating patients with colorectal cancer.

Background: Endogenous sex hormones may contribute to higher colorectal cancer incidence rates in men compared with women, but despite an increased number of studies, clear evidence is lacking. Methods: We conducted a comprehensive nested case–control study of circulating concentrations of sex hormones, sex hormone precursors, and sex hormone binding globulin (SHBG) in relation to subsequent colon cancer risk in European men. Concentrations were measured using liquid LC/MS-MS in prospectively collected plasma samples from 690 cases and 690 matched controls from the European Prospective Investigation into Cancer and Nutrition (EPIC) and the Northern Sweden Health and Disease Study (NSHDS) cohorts. Multivariable conditional logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI). In addition, we conducted a meta-analysis of previous studies on men. Results: Circulating levels of testosterone (OR, 0.68; 95% CI, 0.51–0.89) and SHBG (OR, 0.77; 95% CI, 0.62–0.96) were inversely associated with colon cancer risk. For free testosterone, there was a nonsignificant inverse association (OR, 0.83; 95% CI, 0.58–1.18). In a dose–response meta-analysis of endogenous sex hormone levels, inverse associations with colorectal/colon cancer risk were found for testosterone [relative risks (RR) per 100 ng/dL = 0.98; 95% CI, 0.96–1.00; I2 = 22%] and free testosterone (RR per 1 ng/dL = 0.98; 95% CI, 0.95–1.00; I2 = 0%). Conclusions: Our results provide suggestive evidence for the association between testosterone, SHBG, and male colon cancer development. Impact: Additional support for the involvement of sex hormones in male colon cancer.