No abstract

Colorectal cancer (CRC) represents the third most common type of cancer in developed countries and one of the leading causes of cancer deaths worldwide. Personalized management of CRC has gained increasing attention since there are large inter-individual variations in the prognosis and response to drugs used to treat CRC owing to molecular heterogeneity. Approximately 15% of CRCs are caused by deficient mismatch repair (dMMR) characterized by microsatellite instability (MSI) phenotype. The present review is aimed at highlighting the role of MMR status in informing prognosis and personalized treatment of CRC including adjuvant chemotherapy, targeted therapy, and immune checkpoint inhibitor therapy to guide the individualized therapy of CRC.

IntroductionThis longitudinal study aims to characterize distinct body mass index (BMI) trajectories during early to mid-life adulthood and to explore the association between BMI change from young adulthood to midlife and incident diabetes.Research design and methodsThis study included 7289 adults who had repeatedly measured BMI 3–9 times during 1989–2011 and information on incident diabetes. Latent class growth mixed model (LCGMM) was used to identify different BMI trajectories. Cox proportional hazard models were used to investigate the association between the trajectory group membership and incident hyperglycemia, adjusting for covariates. The hyperglycemia group included individuals with prediabetes or diabetes. The model-estimated BMI levels and slopes were calculated at each age point in 1-year intervals according to the model parameters and their first derivatives, respectively. Logistic regression analyses were used to examine the association of model-estimated levels and slopes of BMI at each age point with incident hyperglycemia. The area under the curve (AUC) was computed from longitudinal growth curve models during the follow-up for each individual. Prior to the logistic regression analyses, quartiles of total, baseline, and incremental AUC values were calculated.ResultsThree distinct trajectories were characterized by LCGMM, comprising of low-increasing group (n=5136), medium-increasing group (n=1914), and high-increasing group (n=239). Compared with the low-increasing group, adjusted HRs and 95% CIs were 1.21 (0.99 to 1.48) and 1.56 (1.06 to 2.30) for the medium-increasing and the high-increasing group, respectively. The adjusted standardized ORs of model-estimated BMI levels increased among 20–50 years, ranging from 0.98 (0.87 to 1.10) to 1.19 (1.08 to 1.32). The standardized ORs of level-adjusted linear slopes increased gradually from 1.30 (1.16 to 1.45) to 1.42 (1.21 to 1.67) during 20–29 years, then decreased from 1.41 (1.20 to 1.66) to 1.20 (1.08 to 1.33) during 30–43 years, and finally increased to 1.20 (1.04 to 1.38) until 50 years. The fourth quartile of incremental AUC (OR=1.31, 95% CI 1.03 to 1.66) was significant compared with the first quartile, after adjustment for covariates.ConclusionsThese findings indicate that the BMI trajectories during early adulthood were significantly associated with later-life diabetes. Young adulthood is a crucial period for the development of diabetes, which has implications for early prevention.