Ubiquitous neurocognitive dysfunction in familial adenomatous polyposis: proof-of-concept of the role of APC protein in neurocognitive function

Background: Familial adenomatous polyposis (FAP) is an autosomal dominant disorder caused by germline mutations in the APC gene. Patients with FAP have multiple extraintestinal manifestations that follow a genotype-phenotype pattern; however, few data exist characterizing their cognitive abilities. Given the role of the APC protein in development of the central nervous system, we hypothesized that patients with FAP would show differences in cognitive functioning compared to controls. Methods: Matched case-control study designed to evaluate cognitive function using the Test of Nonverbal Intelligence-4, the Bateria III Woodcock-Munoz, and the Behavior Rating Inventory of Executive Functions-Adult. Twenty-six individuals with FAP (mean age = 34.2 +/- 15.0 years) and 25 age-gender and educational level matched controls (mean age = 32.7 +/- 13.8 years) were evaluated. Results: FAP-cases had significantly lower IQ (p = 0.005). Across all tasks of the Bateria III Woodcock-Munoz, FAP-cases performed significantly lower than controls, with all of the summary scores falling in the bottom quartile compared to controls (p \u3c 0.0001). Patients with FAP scored within the deficient range for Long-Term Retrieval and Cognitive Fluency. Conclusion: APC protein has an important role in neurocognitive function. The pervasive nature of the observed cognitive dysfunction suggests that loss or dysfunction of the APC protein impacts processes in cortical and subcortical brain regions. Additional studies examining larger ethnically diverse cohorts with FAP are warranted

Association of genetic ancestry with colorectal tumor location in Puerto Rican Latinos

Colorectal cancer (CRC) is the first cause of cancer deaths among Puerto Ricans. The incidence and mortality of CRC in Puerto Rico continue to be on the rise. The burden of CRC in Puerto Rico is higher than among US Hispanics and is second only to African Americans, thus supporting the importance of studying this CRC health disparity. The genetic background of the Puerto Rican population is a mix of European, African, and Amerindian races, which may account, in part, for the differences observed in the CRC mortality rates among Puerto Ricans. The objective of the study was to assess the role of genetic ancestry in CRC risk and its association with clinicopathological features of CRC tumors in Puerto Ricans. We used a validated panel of 105 ancestry informative markers (AIMs) to estimate genetic ancestry in 406 Puerto Rican CRC cases and 425 Puerto Rican controls. We examined the association of genetic ancestry with CRC risk and tumor clinicopathological characteristics. The mean ancestry proportions in the study population were 61% European, 21% African, and 18% Amerindian. No association was observed between genetic ancestry and risk of CRC. However, African ancestry was associated with an increased risk of developing rectal tumors (OR = 1.55, 95% CI 1.04-2.31). Additional studies are needed to fully elucidate the role of African ancestry in CRC carcinogenesis.National Institute on Minority Health and Health Disparities (NIMHD) [MD007587]; National Institute of Allergy and Infectious Diseases (NIAID) [MD007587]; National Cancer Institute (NCI) [CA130034, CA096297/CA096300]; Center for Collaborative Research in Health Disparities RCMI [G12MD007600]Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Hereditary cancer syndromes in Latino populations: genetic characterization and surveillance guidelines

Abstract Hereditary cancer predisposition syndromes comprise approximately 10% of diagnosed cancers; however, familial forms are believed to account for up to 30% of some cancers. In Hispanics, the most commonly diagnosed hereditary cancers include colorectal cancer syndromes such as, Lynch Syndrome, Familial Adenomatous Polyposis, and hereditary breast and ovarian cancer syndromes. Although the incidence of hereditary cancers is low, patients diagnosed with hereditary cancer syndromes are at high-risk for developing secondary cancers. Furthermore, the productivity loss that occurs after cancer diagnosis in these high-risk patients has a negative socio-economic impact. This review summarizes the genetic basis, phenotype characteristics, and the National Comprehensive Cancer Network\u2019s screening, testing, and surveillance guidelines for the leading hereditary cancer syndromes. The aim of this review is to promote a better understanding of cancer genetics and genetic testing in Hispanic patients