Trends in the incidence of early-onset colorectal cancer in all 50 United States from 2001 through 2017.

BACKGROUND: The rate of change in the incidence of colorectal cancer (CRC) among persons younger than 50 years in the United States appears to vary by demographics, tumor location, and geography. This study analyzed data from all 50 states to examine recent changes in the incidence of CRC among persons younger than 50 years and to identify key subgroups with disproportionate risk. METHODS: Annual incidence rates for CRC, colon cancer, and rectal cancer in persons aged 20 to 49 years were extracted from the US Cancer Statistics for the period 2001-2017. Secular trends were examined overall and by age group, sex, race/ethnicity, stage, and state. Joinpoint regression was used to compute annual percent changes and average annual percent changes (AAPCs) as well as corresponding 95% confidence intervals (95% CIs). RESULTS: The incidence of CRC increased by 1.27% (95% CI, 0.95%-1.60%) annually from 2001 to 2012 and by 3.00% (95% CI, 2.06%-3.95%) annually from 2012 to 2017. AAPCs for the period 2001-2017 were higher among persons aged 20 to 24 years (AAPC, 6.62%; 95% CI, 3.86%-9.45%) in comparison with other age groups and higher among non-Hispanic Whites (AAPC, 2.38%; 95% CI, 1.98%-2.79%) in comparison with other racial/ethnic groups. In 2001-2002, only 1 state had an age-standardized incidence rate > 13.0 per 100,000, but this number increased to 32 states by 2016-2017. CONCLUSIONS: CRC rates among US adults aged 20 to 49 years increased from 2001 to 2017, with the fastest increases observed from 2012 to 2017. Increases were observed among the youngest age groups, among non-Hispanic Whites, and in states in the West, Midwest, and Rocky Mountain regions. Increasing rates across all tumor stages suggest a real increase in CRC incidence.

Association Between Inflammatory Bowel Disease and Colorectal Cancer Stage of Disease and Survival.

BACKGROUND: Inflammatory bowel disease (IBD) is associated with an increased risk of colorectal cancer (CRC). However, there are few data comparing outcomes between IBD and non-IBD-associated CRC. METHODS: Retrospective cohort study of patients with CRC identified from the Veteran Affairs (VA) Central Cancer Registry from 1998 to 2012 linked to national VA administrative claims to identify patients with IBD using a previously validated algorithm. The association between IBD status and stage of disease and overall risk of death were evaluated using multivariable logistic and Cox regression, respectively. RESULTS: Among 34,570 CRC patients, 217 had IBD. IBD patients were significantly younger for both colon and rectal cancer. IBD patients who developed rectal cancer were significantly more likely to present with locally advanced or metastatic disease (P = 0.007), but there was no difference in stage among patients with colon cancer. This difference persisted after multivariable adjustment (overall-odds ratio [OR] 1.40, 95% confidence interval [1.03-1.90]; colon-OR 1.22 [0.84-1.78]; rectum-OR 2.04 [1.22-3.40]). Total colectomy was more commonly performed among IBD patients. Overall, IBD was associated with a 52% increased risk of death (hazard ratio 1.52 [1.21-1.91]). CONCLUSIONS: Although IBD is associated with more advanced stage at diagnosis for rectal cancer, it is associated with a worse survival primarily in patients with colon cancer. Further work is needed to better understand the reason for these observed differences between IBD and non-IBD patients and to better delineate the impact of endoscopic surveillance on CRC care and outcomes in IBD patients.

Long-Acting Beta Agonists Enhance Allergic Airway Disease.

Asthma is one of the most common of medical illnesses and is treated in part by drugs that activate the beta-2-adrenoceptor (ß2-AR) to dilate obstructed airways. Such drugs include long acting beta agonists (LABAs) that are paradoxically linked to excess asthma-related mortality. Here we show that LABAs such as salmeterol and structurally related ß2-AR drugs such as formoterol and carvedilol, but not short-acting agonists (SABAs) such as albuterol, promote exaggerated asthma-like allergic airway disease and enhanced airway constriction in mice. We demonstrate that salmeterol aberrantly promotes activation of the allergic disease-related transcription factor signal transducer and activator of transcription 6 (STAT6) in multiple mouse and human cells. A novel inhibitor of STAT6, PM-242H, inhibited initiation of allergic disease induced by airway fungal challenge, reversed established allergic airway disease in mice, and blocked salmeterol-dependent enhanced allergic airway disease. Thus, structurally related ß2-AR ligands aberrantly activate STAT6 and promote allergic airway disease. This untoward pharmacological property likely explains adverse outcomes observed with LABAs, which may be overcome by agents that antagonize STAT6.