Projects beginning in 2000

Impact of MCH genes on breast cancer

The requested samples from the Busselton Survey will be used as part of an overall research plan to examine:-
• candidate disease genes for polymorphisms and mutations in germ-lines, somatic mutations in tumours, and the relative level of gene expression in normal and diseased tissue.
• genomic rearrangements and disturbances within the genomic regions of the candidate disease genes by using microsatellites and retroelements as markers.
Professor Hahnel's collection of breast cancer samples will be used to identify tumour somatic mutations by DNA sequencing and genomic rearrangements of microsatellite and retroelement markers by simple PCR methods. The Busselton Survey sampes will be used as controls to define the sequence variation of candidate genes of Caucasians either with or without disease.

• Assoc Prof Jerzy Kulski, Centre for Immunology and Instrumentation, UWA
• Professor Roland Hahnel, Centre for Immunology and Instrumentation, UWA
• Dr John Beilby, PathCentre
• Professor Hidetoshi Inoko, Dept of Molecular Life Science, Tokai University

Completed

Oka A, Hayashi H, Tomizawa M, Okamoto K, Suyun L, Hui J, Kulski JK, Beilby JP, Tamiya G, Inoko H. Localization of a non-melanoma skin cancer susceptibility region within the major histocompatibility complex by association analysis using microsatellite markers. Tissue Antigens 2003; 61(3):203-210. Abstract

Folate and coronary heart disease mortality

1. To assess in the 1969 Busselton survey cohort if there is an association betwen serum or RBC folate level and subsequent total deaths and cardiovascular deaths.
2. To determine if any association that exists is independent of standard vascular risk factors.

• A/Prof Joe Hung, Dept of Medicine, UWA
• Dr John Beilby, PathCentre
• Prof Matthew Knuiman, School of Population Health, UWA

Completed

Hung J, Beilby JP, Knuiman MW, Divitini ML. Folate and vitamin B-12 and risk of fatal cardiovascular disease: cohort study from Busselton, Western Australia. BMJ 2003; 326: 131-4. Abstract

Establishment of a reference set of cell lines for studies of genetic factors relevant to transplantation, disorders of immune regulation and metabolic disease

1) Identify 200 representative individuals from the Busselton Population and undertake selection based on age and sex.
2) Establish EBV transformed lymphoblastoid cell lines on these individuals.
3) Propagate these cells, extract DNA from them and freeze aliquots of the cell lines for storage in two seperate sites. Aliquots of the DNA should also be stored at two separate sites.
4) Progressively use this material for typing of the following genes:
i. HLA and non-HLA genes within the MHC relevant to transplantaion outcome and disease susceptibility
ii. Minor histocompatibility genes and other genes relevant to donor recipient matching for transplantation purposes.
iii. Genes encoding for cytokines and cytokine receptors which are relevant to transplantation and to disease.
iv. Those genes for which the Department of Clinical Immunology and Biochemical Genetics provides a routine diagnostic service.
v. Candidate genes for coronary artery disease and dyslipidaemia.
5. To utilise this reference material for determining diagnostic utility of these polymorphisms, control frequencies in disease studies, and for transplantation purposes.

• Assoc Prof Frank Christiansen, Dept of Clinical Immunology, RPH
• Dr Peter Hollingsworth, Dept of Clinical Immunology, PathCentre
• Dr Campbell Witt, Dept of Clinical Immunology, RPH
• Mr Steve Pummer, Dept of Clinical Immunology, RPH

In progress

The incidence of androgen deficiency determined by calculated free testosterone in elderly males in the Busselton population

1. Determine the prevalence of androgen deficiency in a population based sample of elderly men using a reference range dervied from young male subjects in the same population.
2. Compare the measurement of serum testosterone levels determined by total testosterone level with that derived from calculated free testosterone using sex hormone-binding globulin (SHBG), albumin and total testosterone, and examine the comparability of these measures at different ages.

• Dr Jonathan Beilin, Dept of Endocrinology and Diabetes, Royal Perth Hospital
• Assoc Prof Peter Leedman, Dept of Endocrinology and Diabetes, Royal Perth Hospital
• Dr Gerard Chew, Dept of Endocrinology and Diabetes, Royal Perth Hospital

In progress

Lymphocyte activation and inflammation markers predict risk of future coronary events - a prospective study of the Busselton Health Survey population

1. To determine the association between serum markers of inflammation and lymphocyte activation and the subsequent development of myocardial infarction or stroke in the Busselton Health Survey.
2. To determine the interaction between serum markers of lymphocyte activation and inflammation, and the classical cardiovascular risk factors of cholesterol, blood pressure, diabetes and cigarette smoking level on subsequent risk of cardiovascular events in this population.

• Dr Paul Langton, Dept of Medicine, UWA
• A/Prof Joe Hung, Dept of Medicine, UWA
• Prof Matthew Knuiman, School of Population Health, UWA
• Dr Peter Hollingsworth, Dept of Clinical Immunology, PathCentre
• Dr John Beilby, Dept of Clinical Biochemistry, PathCentre

In progress