Rising trends in the incidence and mortality of early-onset CRC in those who are ages less than 50 years have been well-established. These trends have spurred intense investigation focused on elucidating the epidemiology and characteristics of early-onset CRC, as well on identifying strategies for early detection and prevention. In this review, we provide a contemporary update on early-onset CRC with a particular focus on epidemiology, molecular characterization, red flag signs and symptoms, and screening for early-onset CRC.

An expanding body of evidence supports a role for gut microbes in the etiology of cancer. Previously, the focus was on identifying individual bacterial species that directly initiate or promote gastrointestinal malignancies; however, the capacity of gut microbes to influence systemic inflammation and other downstream pathways suggests that the gut microbial community may also affect risk of cancer in tissues outside of the gastrointestinal tract. Functional contributions of the gut microbiota that may influence cancer susceptibility in the broad sense include (1) harvesting otherwise inaccessible nutrients and/or sources of energy from the diet (i.e., fermentation of dietary fibers and resistant starch); (2) metabolism of xenobiotics, both potentially beneficial or detrimental (i.e., dietary constituents, drugs, carcinogens, etc.); (3) renewal of gut epithelial cells and maintenance of mucosal integrity; and (4) affecting immune system development and activity. Understanding the complex and dynamic interplay between the gut microbiome, host immune system, and dietary exposures may help elucidate mechanisms for carcinogenesis and guide future cancer prevention and treatment strategies.

Colorectal adenomas are clear precursors of cancer; hyperplastic polyps may also have malignant potential. An inverse association between circulating vitamin D metabolites and adenoma risk has been reported, but less is known about vitamin D and hyperplastic polyps. We conducted a case-control study of adenomas and hyperplastic polyps among 459 members of an integrated health plan evaluated via colonoscopy. Questionnaires provided information on colorectal polyp risk factors, and plasma samples were assayed for 25-hydroxyvitamin-D (25(OH)D). Polytomous regression was used to estimate odds ratios for adenomas (N=149) and hyperplastic polyps (N=85) compared to polyp-free controls (N=225) by tertile of 25(OH)D. An inverse association between 25(OH)D and adenomas was suggested after adjustment for potential confounding factors (comparing upper to lower tertiles, OR[95%CI]: 0.71 [0.38–1.30]). After restriction of the analyses to study participants with no history of polyps, this OR estimate was reduced further (adjusted OR [95%CI]: 0.52 [0.23–1.20]). In comparison, no inverse association between hyperplastic polyps and 25(OH)D was observed among the full study participants (adjusted OR [95%CI]: 1.17 [0.55–2.51]) or among those without prior polyps (adjusted OR [95%CI]: 1.42 [0.55–3.65]). Our study suggests that the established inverse association between circulating 25(OH)D and adenoma may not apply to hyperplastic polyps.

BACKGROUND Although combustible cigarette use is an established risk factor for severe COVID-19 disease, there is conflicting evidence for the association of electronic cigarette use with SARS-CoV-2 infection and COVID-19 disease severity. METHODS Study participants were from the Kaiser Permanente Research Bank (KPRB), a biorepository that includes adult Kaiser Permanente members from across the United States. Starting in April 2020, electronic surveys were sent to KPRB members to assess the impact of the COVID-19 pandemic. These surveys collected information on self-report of SARS-CoV-2 infection and COVID-related risk factors, including electronic cigarette and combustible cigarette smoking history. We also used electronic health records data to assess COVID-19 diagnoses, positive PCR lab tests, hospitalizations, and death. We used multivariable Cox proportional hazards regression to calculate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) comparing the risk of SARS-CoV-2 infection between individuals by e-cigarette use categories (never, former, and current). Among those with SARS-CoV-2 infection, we used multivariable logistic regression to estimate adjusted odds ratios (ORs) and 95% CIs comparing the odds of hospitalization or death within 30 days of infection between individuals by e-cigarette use categories. RESULTS There were 126,475 individuals who responded to the survey and completed questions on e-cigarette and combustible cigarette use (48% response rate). Among survey respondents, 819 (1%) currently used e-cigarettes, 3,691 (3%) formerly used e-cigarettes, and 121,965 (96%) had never used e-cigarettes. After adjustment for demographic, behavioral, and clinical factors, there was no association with SARS-CoV-2 infection and former e-cigarette use (hazard ratio (HR) = 0.99; CI: 0.83–1.18) or current e-cigarette use (HR = 1.08; CI: 0.76–1.52). Among those with SARS-CoV-2 infection, there was no association with hospitalization or death within 30 days of infection and former e-cigarette use (odds ratio (OR) = 1.19; CI: 0.59–2.43) or current e-cigarette use (OR = 1.02; CI: 0.22–4.74). CONCLUSIONS Our results suggest that e-cigarette use is not associated with an increased risk of SARS-CoV-2 infection or severe COVID-19 illness.