M. Holmes1, K. Bolton2,3, B. Talseth-Palmer2,3, P. Pockney1,4, R. Scott1,2,3 1Hunter New England Local Health District,Newcastle, NSW, Australia 2Hunter Medical Research Institute,Newcastle, NSW, Australia 3University Of Newcastle,Discipline Of Medical Genetics, School Of Biomedical Science And Pharmacy,Newcastle, NSW, Australia 4University Of Newcastle,School Of Medicine And Public Health,Newcastle, NSW, Australia
Introduction: Familial Adenomatous Polyposis (FAP) is a hereditary syndrome that predisposes individuals to developing hundreds to thousands of adenomatous polyps predominantly in the colon. There is an almost 100% lifetime risk that these individuals will go on to develop colorectal cancer (CRC). The development of FAP is largely due to a germline mutation in the adenomatous polyposis coli (APC) gene. In recent years significant variability in phenotypic expression of FAP has been found in individuals carrying the same APC mutation. Ongoing research has supported the theory that this variability in phenotype may be the result of modifier genes. Identifying modifier genes in human populations has proven difficult and mouse models have been used to help identify a number of possible modifier genes. Recently a potential candidate gene for a mouse gene modifier was identified, CD36, with a demonstrated impact on tumorigenesis1. This study aimed to investigate if single nucleotide polymorphisms (SNPs) in the CD36 gene could act as modifier genes for colon cancer development in human FAP patients.
Methods: DNA from 143 FAP patients with an APC germline mutation was obtained from the Hunter Area Pathology Service, Newcastle, NSW, and genotyped using 3 SNP assays. Polymerase chain reaction (PCR) was performed and read. Data recording extent of disease, presence of genetic mutations, age at diagnosis and intervention had been previously collated.
Results: Kaplan-Meier analysis was suggestive of a protective effect in patients carrying the homozygote variant genotype of the SNP rs1984112, with none of these patients developing CRC in the follow up period.
Conclusion:
These findings are suggestive of the existence of a disease modifiying gene which may have a significant impact on the clinical management of these patients. A larger validation cohort is currently being sought to further investigate. This method could be used to investigate other potential modifier genes.
Reference:
1. Otterpohl KL, Gould KA: Genetic dissection of the Mom5 modifier locus and evaluation of Mom5 candidate genes. Mamm Genome. 2015 Jun;26(5-6):235-47.