Genetic predisposition to colorectal cancer: syndromes, genes, classification of genetic variants and implications for precision medicine

This article reviews genes and syndromes associated with predisposition to colorectal cancer (CRC), with an overview of gene variant classification. We include updates on the application of preventive and therapeutic measures, focusing on the use of non-steroidal anti-inflammatory drugs (NSAIDs) and immunotherapy. Germline pathogenic variants in genes conferring high or moderate risk to cancer are detected in 6-10% of all CRCs and 20% of those diagnosed before age 50. CRC syndromes can be subdivided into nonpolyposis and polyposis entities, the most common of which are Lynch syndrome and familial adenomatous polyposis, respectively. In addition to known and novel genes associated with highly penetrant CRC risk, identification of pathogenic germline variants in genes associated with moderate-penetrance cancer risk and/or hereditary cancer syndromes not traditionally linked to CRC may have an impact on genetic testing, counseling, and surveillance. The use of multigene panels in genetic testing has exposed challenges in the classification of variants of uncertain significance. We provide an overview of the main classification systems and strategies for improving these. Finally, we highlight approaches for integrating chemoprevention in the care of individuals with genetic predisposition to CRC and use of targeted agents and immunotherapy for treatment of mismatch repair-deficient and hypermutant tumors. Copyright (c) 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd

Germline genetic variants in men with prostate cancer and one or more additional cancers

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/138930/1/cncr30817.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/138930/2/cncr30817_am.pd

Working up rectal bleeding in adult primary care practices

Rationale, aims and objectivesVariation in the workup of rectal bleeding may result in guideline‐discordant care and delayed diagnosis of colorectal cancer. Accordingly, we undertook this study to characterize primary care clinicians’ initial rectal bleeding evaluation.MethodsWe studied 438 patients at 10 adult primary care practices affiliated with three Boston, Massachusetts, academic medical centres and a multispecialty group practice, performing medical record reviews of subjects with visit codes for rectal bleeding, haemorrhoids or bloody stool. Nurse reviewers abstracted patients’ sociodemographic characteristics, rectal bleeding‐related symptoms and components of the rectal bleeding workup. Bivariate and multivariable logistic regression models examined factors associated with guideline‐discordant workups.ResultsClinicians documented a family history of colorectal cancer or polyps at the index visit in 27% of cases and failed to document an abdominal or rectal examination in 21% and 29%. Failure to order imaging or a diagnostic procedure occurred in 32% of cases and was the only component of the workup associated with guideline‐discordant care, which occurred in 27% of cases. Compared with patients at hospital‐based teaching sites, patients at urban clinics or community health centres had 2.9 (95% confidence interval 1.3–6.3) times the odds of having had an incomplete workup. Network affiliation was also associated with guideline concordance.ConclusionWorkup of rectal bleeding was inconsistent, incomplete and discordant with guidelines in one‐quarter of cases. Research and improvements strategies are needed to understand and manage practice and provider variation.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/136454/1/jep12596.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/136454/2/jep12596_am.pd

An oncocytic adrenal tumour in a patient with Birt‐Hogg‐Dubé syndrome

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/106917/1/cen12292.pd