The presence of () in colorectal carcinoma tissue has been associated with microsatellite instability (MSI), lower-level T-cell infiltrates, and poor clinical outcomes. Considering differences in the tumor-immune microenvironment between MSI-high and non-MSI-high carcinomas, we hypothesized that the association of with immune response might differ by tumor MSI status. Using samples from 1,041 rectal and colon cancer patients within the Nurses' Health Study and Health Professionals Follow-up Study, we measured DNA in tumor tissue by a quantitative polymerase chain reaction assay. Multivariable logistic regression models were used to examine the association between status and histopathologic lymphocytic reactions or density of CD3 cells, CD8 cells, CD45RO (PTPRC) cells, or FOXP3 cells in strata of tumor MSI status. We adjusted for potential confounders, including CpG island methylator phenotype; LINE-1 methylation; and , and mutations. The association of with tumor-infiltrating lymphocytes (TIL) and intratumoral periglandular reaction differed by tumor MSI status ( = 0.002). The presence of was negatively associated with TIL in MSI-high tumors [multivariable odds ratio (OR), 0.45; 95% confidence interval (CI), 0.22-0.92], but positively associated with TIL in non-MSI-high tumors (multivariable OR 1.91; 95% CI, 1.12-3.25). No significant differential association was observed for peritumoral lymphocytic reaction, Crohn-like lymphoid reaction, or T-cell densities. In conclusion, the association of with immune response to colorectal carcinoma differs by tumor MSI status, suggesting that and MSI status interact to affect antitumor immune reactions. .

Diets that may promote intestinal inflammation, based on EDIP score, are associated with increased risk of F nucleatum-positive colorectal carcinomas, but not carcinomas that do not contain these bacteria. These findings indicate that diet-induced intestinal inflammation alters the gut microbiome to contribute to colorectal carcinogenesis; nutritional interventions might be used in precision medicine and cancer prevention.

SummaryBackground and objectives Glomerular hyperfiltration and albuminuria accompanied by early-stage diabetic kidney disease predict future renal failure. Cigarette smoking has reported to be associated with elevated GFR in cross-sectional studies and with renal deterioration in longitudinal studies. The degree of glomerular hyperfiltration and proteinuria associated with smoking, which presumably is a phenomenon of early renal damage, has not been investigated in a satisfying manner so far. Design, setting, participants, & measurementsThis study included 10,118 Japanese men aged 40 to 55 years without proteinuria or renal dysfunction at entry. Estimated GFR was calculated using the Modification of Diet in Renal Disease equation for Japanese. Glomerular hyperfiltration was defined as estimated GFR Ն117.0 ml/min per 1.73 m 2 , which was the upper 2.5th percentile value of estimated GFR in the total population. Proteinuria was detected using standard dipstick.Results During the 6-year observation period, there were 449 incident cases of glomerular hyperfiltration and 1653 cases of proteinuria. Current smokers had a 1.32-time higher risk for the development of glomerular hyperfiltration and a 1.51-time higher risk for proteinuria than nonsmokers after adjustment for baseline age, body mass index, systolic and diastolic BP, antihypertensive medication, diabetes, alcohol consumption, regular leisure-time physical activity, and estimated GFR. Both daily and cumulative cigarette consumption were associated with an increased risk for glomerular hyperfiltration and proteinuria in a doseresponse manner. ConclusionsIn middle-aged Japanese men, smoking was associated with an increased risk of glomerular hyperfiltration and dipstick proteinuria. Of importance, past smokers did not exhibit any increased risk for these conditions.