CD36 - a plausible modifier of disease phenotype in familial adenomatous polyposis

Merran Holmes; Toni Connor; Christopher Oldmeadow; Peter G Pockney; Rodney J Scott; Bente A Talseth-Palmer

doi:10.1186/s13053-018-0096-y

CD36 - a plausible modifier of disease phenotype in familial adenomatous polyposis

Hered Cancer Clin Pract. 2018 Jul 28:16:14. doi: 10.1186/s13053-018-0096-y. eCollection 2018.

Authors

Merran Holmes^#^{1

2}, Toni Connor^#^{1

3}, Christopher Oldmeadow⁴, Peter G Pockney^{1

2}, Rodney J Scott^{3

5}, Bente A Talseth-Palmer^{5

6

7}

Affiliations

¹ 1School of Medicine and Public Health, Faculty of Health and Medicine, University of Newcastle, Newcastle, NSW Australia.
² 2Department of Surgery, John Hunter Hospital, Newcastle, Australia.
³ Pathology North, NSW Health Pathology, Newcastle, Australia.
⁴ 4Centre for Clinical Epidemiology and Biostatistics, University of Newcastle, Newcastle, NSW Australia.
⁵ 5School of Biomedical Science and Pharmacy, Faculty of Health and Medicine, University of Newcastle and Hunter Medical Research Institute, Newcastle, Australia.
⁶ 6Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway.
⁷ Clinic for Medicine, Møre og Romsdal Hospital Trust, Molde, Norway.

^# Contributed equally.

Abstract

Background: Familial adenomatous polyposis (FAP) is a well characterised genetic predisposition to early onset colorectal cancer (CRC) that is characterised by polyposis of the colon and rectum. Animal models have consistently suggested the role of modifier genes in determining disease phenotype, yet none have been substantiated in the human population. The mouse homologue of cluster of differentiation 36 (CD36) has been proposed as a modifier of disease in the MIN mouse model of FAP.

Methods: Three single nucleotide polymorphisms (SNPs); rs1049673, rs1761667 and rs1984112 in CD36, have been investigated in 275 FAP patients to determine if they were associated with age of polyposis or risk of developing disease.

Results: The results revealed a substantially lower age of polyposis diagnosis for patients belonging to the severe FAP group (harbouring adenomatous polyposis coli (APC) variants in the mutation cluster region (MCR)) and high age for patients in the attenuated familial adenomatous polyposis (AFAP) group for SNPs rs1761667 and rs1984112.

Conclusions: This study provides evidence for patients belonging to the MCR and AFAP groups harbouring specific genotypes for SNPs in CD36 to initiate screening/treatment for FAP at much earlier (MCR) and much later (AFAP) ages than the norm in today's clinical practice. The findings need to be verified in an independent FAP patient cohort.

Keywords: CD36; Disease phenotype; FAP; Modifier gene; Polyposis.