title: A polymorphic repeat in the IGF1 promoter influences the risk of endometrial cancer.
abstract: Due to the lack of high-throughput genetic assays for tandem repeats, there is a paucity of knowledge about the role they may play in disease. A polymorphic CA repeat in the promoter region of the insulin-like growth factor 1 gene (IGF1 has been studied extensively over the past 10 years for association with the risk of developing breast cancer, among other cancers, with variable results. The aim of this study was to determine if this CA repeat is associated with the risk of developing breast cancer and endometrial cancer. Using a case-control design, we analysed the length of this CA repeat in a series of breast cancer and endometrial cancer cases and compared this with a control population. Our results showed an association when both alleles were considered in breast and endometrial cancers (P=0.029 and 0.011, respectively), but this did not pass our corrected threshold for significance due to multiple testing. When the allele lengths were analysed categorically against the most common allele length of 19 CA repeats, an association was observed with the risk of endometrial cancer due to a reduction in the number of long alleles (P=0.013). This was confirmed in an analysis of the long alleles separately for endometrial cancer risk (P=0.0012). Our study found no association between the length of this polymorphic CA repeat and breast cancer risk. The significant association observed between the CA repeat length and the risk of developing endometrial cancer has not been previously reported.
authors.affiliation: Centre for BioinformaticsBiomarker Discovery and Information-Based Medicine, Hunter Medical Research Institute, Newcastle, New South Wales, Australia Priority Research Centre for CancerSchool of Biomedical Sciences and Pharmacy, Faculty of Health and Medicine, University of Newcastle, Newcastle, New South Wales, Australia.
authors.forename: Katherine A
authors.initials: KA
authors.lastname: Bolton
authors.affiliation: Centre for BioinformaticsBiomarker Discovery and Information-Based Medicine, Hunter Medical Research Institute, Newcastle, New South Wales, Australia Priority Research Centre for CancerSchool of Biomedical Sciences and Pharmacy, Faculty of Health and Medicine, University of Newcastle, Newcastle, New South Wales, Australia.
authors.forename: Kelly A
authors.initials: KA
authors.lastname: Avery-Kiejda
authors.affiliation: Centre for Clinical Epidemiology and BiostatisticsSchool of Medicine and Public Health, Faculty of Health and Medicine, University of Newcastle, Newcastle, New South Wales, Australia Clinical Research DesignIT and Statistical Support Unit, Hunter Medical Research Institute, Newcastle, New South Wales, Australia.
authors.forename: Elizabeth G
authors.initials: EG
authors.lastname: Holliday
authors.affiliation: Centre for Clinical Epidemiology and BiostatisticsSchool of Medicine and Public Health, Faculty of Health and Medicine, University of Newcastle, Newcastle, New South Wales, Australia Clinical Research DesignIT and Statistical Support Unit, Hunter Medical Research Institute, Newcastle, New South Wales, Australia.
authors.forename: John
authors.initials: J
authors.lastname: Attia
authors.affiliation: Centre for BioinformaticsBiomarker Discovery and Information-Based Medicine, Hunter Medical Research Institute, Newcastle, New South Wales, Australia Priority Research Centre for CancerSchool of Biomedical Sciences and Pharmacy, Faculty of Health and Medicine, University of Newcastle, Newcastle, New South Wales, Australia.
authors.forename: Nikola A
authors.initials: NA
authors.lastname: Bowden
authors.affiliation: Centre for BioinformaticsBiomarker Discovery and Information-Based Medicine, Hunter Medical Research Institute, Newcastle, New South Wales, Australia Priority Research Centre for CancerSchool of Biomedical Sciences and Pharmacy, Faculty of Health and Medicine, University of Newcastle, Newcastle, New South Wales, Australia Molecular MedicinePathology North, John Hunter Hospital, Newcastle, New South Wales, Australia Discipline of Medical GeneticsSchool of Biomedical Sciences and Pharmacy, Faculty of Health and Medicine, University of Newcastle, University Drive, Newcastle, New South Wales, Australia rodney.scott@newcastle.edu.au.
authors.forename: Rodney J
authors.initials: RJ
authors.lastname: Scott
keywords: IGF1 gene; breast cancer; endometrial cancer; promoter region; short tandem repeat