Colorectal cancer in the setting of pregnancy and familial risk.

Background And Aims: Women are at risk of colorectal cancer (CRC) during pregnancy but this fact is underappreciated. We performed a population-based study to evaluate the rate, predictors, and familial risk for pregnancy associated CRC in Utah.

Methods: All newly diagnosed cases of CRC between 1973 and 2014 were obtained from the Utah Cancer Registry and linked to pedigrees from the Utah Population Database.

Use of Family History and Genetic Testing to Determine Risk of Colorectal Cancer.

Approximately 35% of patients with colorectal cancer (CRC) have a family history of the disease attributed to genetic factors, common exposures, or both. Some families with a history of CRC carry genetic variants that cause CRC with high or moderate penetrance, but these account for only 5% to 10% of CRC cases. Most families with a history of CRC and/or adenomas do not carry genetic variants associated with cancer syndromes; this is called common familial CRC.

Familial pancreatic cancer risk: a population-based study in Utah.

Introduction: Pancreas adenocarcinoma (PC) has an undefined hereditary component. We quantified the familial risk of PC among relatives of patients diagnosed with PC and stratified it based on anatomic location of PC and age and sex of the proband.

Methods: This is a retrospective, population-based, case-control study of PC diagnosed in Utah between 1980 and 2011.

Clinical and Molecular Features of Post-Colonoscopy Colorectal Cancers.

Background & Aims: Post-colonoscopy colorectal cancers (PCCRCs) may arise from missed lesions or due to molecular features of tumors that allow them to grow rapidly. We aimed to compare clinical, pathology, and molecular features of PCCRCs (those detected within 6-60 months of colonoscopy) and detected CRCs (those detected within 6 months of a colonoscopy).

Methods: Within a population-based cross-sectional study of incident CRC cases in Utah (from 1995 through 2009), we identified PCCRCs (those cancers that developed within 5 years of a colonoscopy) and matched the patients by age, sex, and hospital site to patients with detected CRC.

Family History Associates With Increased Risk of Colorectal Cancer in Patients With Inflammatory Bowel Diseases.

Background & Aims: Individuals with inflammatory bowel diseases (IBDs) have an increased risk of developing colorectal cancer (CRC). Although family history of CRC is a well-established risk factor in healthy individuals, its role in patients with IBD is less clear. We aimed to estimate the risk of CRC in a cohort of patients with IBD from Utah and the significance of family history of CRC in a first-degree relative (FDR).

Small RNA sequencing of sessile serrated polyps identifies microRNA profile associated with colon cancer.

Sessile serrated adenoma/polyps (SSA/Ps) of the colon account for 20-30% of all colon cancers. Small non-coding RNAs, including microRNAs (miRNAs), may function as oncogenes or tumor suppressor genes involved in cancer development. Small RNA sequencing (RNA-seq) was used to characterize miRNA profiles in SSA/Ps, hyperplastic polyps (HPs), adenomatous polyps and paired uninvolved colon.

Variables affecting penetrance of gastric and duodenal phenotype in familial adenomatous polyposis patients.

Background: Patients with familial adenomatous polyposis (FAP) frequently undergo colectomy to reduce the 70 to 90% lifetime risk of colorectal cancer. After risk-reducing colectomy, duodenal cancer and complications from duodenal surgeries are the main cause of morbidity. Our objective was to prospectively describe the duodenal and gastric polyp phenotype in a cohort of 150 FAP patients undergoing pre-screening for a chemoprevention trial and analyze variables that may affect recommendations for surveillance.

Active BRAF-V600E is the key player in generation of a sessile serrated polyp-specific DNA methylation profile.

Background: Sessile serrated polyps (SSPs) have emerged as important precursors for a large number of sporadic colorectal cancers. They are difficult to detect during colonoscopy due to their flat shape and the excessive amounts of secreted mucin that cover the polyps. The underlying genetic and epigenetic basis for the emergence of SSPs is largely unknown with existing genetic studies confined to a limited number of oncogenes and tumor suppressors.

Association of Sulindac and Erlotinib vs Placebo With Colorectal Neoplasia in Familial Adenomatous Polyposis: Secondary Analysis of a Randomized Clinical Trial.

Importance: Patients with familial adenomatous polyposis (FAP) are at markedly increased risk for colorectal polyps and cancer. A combination of sulindac and erlotinib led to a 71% reduction in duodenal polyp burden in a phase 2 trial.

Objective: To evaluate effect of sulindac and erlotinib on colorectal adenoma regression in patients with FAP.

Chemoprevention with Cyclooxygenase and Epidermal Growth Factor Receptor Inhibitors in Familial Adenomatous Polyposis Patients: mRNA Signatures of Duodenal Neoplasia.

To identify gene expression biomarkers and pathways targeted by sulindac and erlotinib given in a chemoprevention trial with a significant decrease in duodenal polyp burden at 6 months ( < 0.001) in familial adenomatous polyposis (FAP) patients, we biopsied normal and polyp duodenal tissues from patients on drug versus placebo and analyzed the RNA expression. RNA sequencing was performed on biopsies from the duodenum of FAP patients obtained at baseline and 6-month endpoint endoscopy.

Cancer Risk in Families Fulfilling the Amsterdam Criteria for Lynch Syndrome.

Importance: The data describing cancer risks associated with Lynch syndrome are variable.

Objectives: To quantify the prevalence of families that fulfill the Amsterdam I or II criteria for Lynch syndrome in the Utah population and investigate the risk of colonic and extracolonic cancers in family members and their relatives.

Design, Setting, And Participants: In a population-based study, 202 families with Amsterdam I and II criteria–positive pedigrees in the Utah Population Database were identified.

Long-Term Colorectal Cancer Incidence After Negative Colonoscopy in the State of Utah: The Effect of Family History.

Objectives: Colonoscopy is widely recommended for colorectal cancer (CRC) screening, but evidence to guide the optimal frequency of repeat screening examination is limited. We examined the duration and magnitude of the risk of developing CRC, following a negative colonoscopy in those at average risk and those with a first-degree family history of CRC.

Methods: A cohort of Utah residents aged 50-80 years who had a negative colonoscopy between 1 January 2001 and 31 December 2011 was identified using the Utah Population Database.

Reducing the polyp burden in serrated polyposis by serial colonoscopy: the impact of nationally coordinated community surveillance.

Background: Serrated polyposis syndrome (SPS) is associated with an increased risk of colorectal cancer (CRC) and an evolving management approach. The aims of this study were to assess the polyp burden reduction over time, and the incidence of CRC in serrated polyposis patients undergoing community surveillance.

Methods: This is an observational study based on prospectively collected data.

Colorectal Cancer in Inflammatory Bowel Diseases: A Population-Based Study in Utah.

Background And Aims: The molecular, endoscopic, and histological features of IBD-associated CRC differ from sporadic CRC. The objective of this study was to describe the prevalence, clinical features, and prognosis of IBD-associated CRC compared to patients with sporadic CRC in a US statewide population-based cohort.

Methods: All newly diagnosed cases of CRC between 1996 and 2011 were obtained from Utah Cancer Registry.

A role for the vitamin D pathway in non-intestinal lesions in genetic and carcinogen models of colorectal cancer and in familial adenomatous polyposis.

Vitamin D is implicated in the etiology of cancers of the gastrointestinal tract, usually characterized by alteration in the APC/β-catenin/TCF tumor suppressor pathway. The vitamin D receptor (VDR) is also implicated in cardiovascular and skin diseases as well as in immunity. Activated VDR can indirectly alter β-catenin nuclear localization and directly suppress β-catenin/TCF mediated transcriptional activity.

Gastrointestinal Polyposis in Cowden Syndrome.

Goals: To further characterize the gastrointestinal manifestations of Cowden syndrome in clinically well-annotated patients to improve the diagnosis of this syndrome.

Background: The gastrointestinal manifestations of Cowden Syndrome, an important heritable and multiorgan cancer syndrome, are not well defined. Proper diagnosis is essential for effective cancer surveillance and prevention in these patients.

Familial Risk of Biliary Tract Cancers: A Population-Based Study in Utah.

Background And Objectives: Biliary tract cancers (BTC) including, cholangiocarcinoma (CC) and gallbladder cancer (GBC), are rare and highly fatal malignancies. The etiology and inherited susceptibility of both malignancies are poorly understood. We quantified the risk of BTC in first-degree (FDR), second-degree (SDR), and first cousin (FC) relatives of individuals with BTC, stratified by tumor subsite.

Understanding the contribution of family history to colorectal cancer risk and its clinical implications: A state-of-the-science review.

Persons with a family history (FH) of colorectal cancer (CRC) or adenomas that are not due to known hereditary syndromes have an increased risk for CRC. An understanding of these risks, screening recommendations, and screening behaviors can inform strategies for reducing the CRC burden in these families. A comprehensive review of the literature published within the past 10 years has been performed to assess what is known about cancer risk, screening guidelines, adherence and barriers to screening, and effective interventions in persons with an FH of CRC and to identify FH tools used to identify these individuals and inform care.

Gene Signature in Sessile Serrated Polyps Identifies Colon Cancer Subtype.

Sessile serrated colon adenoma/polyps (SSA/P) are found during routine screening colonoscopy and may account for 20% to 30% of colon cancers. However, differentiating SSA/Ps from hyperplastic polyps (HP) with little risk of cancer is challenging and complementary molecular markers are needed. In addition, the molecular mechanisms of colon cancer development from SSA/Ps are poorly understood.

Effect of Sulindac and Erlotinib vs Placebo on Duodenal Neoplasia in Familial Adenomatous Polyposis: A Randomized Clinical Trial.

Importance: Patients with familial adenomatous polyposis (FAP) are at markedly increased risk for duodenal polyps and cancer. Surgical and endoscopic management of duodenal neoplasia is difficult and chemoprevention has not been successful.

Objective: To evaluate the effect of a combination of sulindac and erlotinib on duodenal adenoma regression in patients with FAP.

Familial Risk in Patients With Carcinoma of Unknown Primary.

Importance: Carcinoma of unknown primary (CUP) accounts for 3% to 5% of all cancers and is associated with poor prognosis. Familial clustering of different cancer sites with CUP is unknown and may provide information regarding etiology, as well as elevated cancer risks in relatives.

Objective: To quantify the risk of cancer by site in first- and second-degree relatives and first cousins of individuals with CUP.

Morphologic characterization of hamartomatous gastrointestinal polyps in Cowden syndrome, Peutz-Jeghers syndrome, and juvenile polyposis syndrome.

The morphologic features of the gastrointestinal polyps in hamartomatous polyposis syndromes are poorly defined. Our aim was to better characterize the gastrointestinal hamartomas in these syndromes. A blinded review was performed regarding many histologic features for every polyp.