Professor Tim Bishop
- Position: Professor of Genetic Epidemiology
- Areas of expertise: Epidemiology; genetics; statistical genetics; cancer.
- Email: D.T.Bishop@leeds.ac.uk
- Phone: +44(0)113 206 5041
- Location: 6.03 Clinical Sciences Building
- Website: genomel | Googlescholar | ORCID
I hold a BSc in Mathematics and Computer Science from the University of Bristol and an MSc from the same University in Statistics. My PhD. was awarded in 1978 by the University of Sheffield in Probability and Statistics; the topic was the application of game theory to modelling animal conflicts.
In 1977, I moved to the University of Utah, Salt Lake City, for a post-doc (followed by Faculty appointments) to work with Professor Mark Skolnick and the late Professor Roger Williams developing statistical approaches to study disease aggregation in families. As part of our activities, we worked on early approaches to use recombinant DNA technology to study and utilize genetic variation to understand human disease. As such, we were highly involved in the early phases of the Human Genome Project and in applying the rudimentary map to map and clone disease genes, notably genes associated with neurofibromatosis, haemochromatosis, breast cancer, bowel cancer and melanoma. The initial success with finding NF1 (the neurofibromatosis gene) and understanding the association between haemochromatosis and HLA showed the potential for the technology.
I was recruited to Leeds by the Imperial Cancer Research Fund (now Cancer Research UK) in 1989 to develop a Genetic Epidemiology Unit associated with the University of Leeds. Cancer Research UK has supported our activities since that time.
My research aims to:
a) identify the genes and the specific germline variation which influences a person’s risk of developing cancer and/or surviving that cancer
b) quantify the impact of this genetic variation within the general population and
c) the understand the joint effects of this genetic variation together with non-genetic exposures as modifiers of this risk and/or outcome.
Melanoma skin cancer rates are increasing and until recently there were no treatment options other than surgery. Risk has been long known to be associated with pigmentation and numbers of skin naevi (benign lesions); both of these traits are highly heritable. We have conducted large-scale recruitment of melanoma cases locally and nationally to (i) identify further genetic variation associated with melanoma risk (and categorise by risk phenotype), (ii) determine the high risk profile UV exposure (the main environmental exposure for melanoma), (iii) examine the joint effects of pattern of UV exposure and genetic susceptibility and (iv) determine the determinants of survival after a diagnosis of melanoma – especially as to how this involves the genetic makeup of the tumour and the immune system. For such activities, we have brought together extensive case recruitment primarily in the local region and international collaborations through the shared community of GenoMEL,
Studies of high penetrance risk have been particularly successful in identifying the precise genetic mechanisms underlying susceptibility. These mechanisms have included failure of such basic processes as DNA repair and/or cell cycle regulation. Cancer risks tend to be high, although variable, within particular families. With Professor Richard Kolodner, my team showed that germline mutations in the mismatch repair genes (MLH1, MSH2) were responsible for the syndrome Hereditary Non-Polyposis Colorectal Cancer (HNPCC, alternatively known as Lynch Syndrome). Lifetime risk for colorectal cancer in men is around 60% with a somewhat lower risk for females but the high risk of endometrial cancer means that overall the cancer burden is very similar between males and females within these families.
Epidemiological literature suggests that regular aspirin usage (or other NSAIDs) is associated with a lower risk of bowel cancer and so in a close collaboration with Professor Sir John Burn and Professor John Mathers at the University of Newcastle, we developed a study addressing the protective effect of aspirin (the CAPP2 study). This study confirmed that persons with germ-line mutations in mismatch repair genes, who took aspirin (600mg per day) for at least 2 years, halved their cancer risk for the next 5 years. CAPP3 is now underway, it focuses on a similar cohort of patients and is trying to identify the appropriate dose of aspirin to have a protective effect on bowel neoplasia while minimising the risk of side effects from the aspirin.
- Ph.D. (University of Sheffield, Probability and Statistics)
- M.Sc. (University of Bristol, Statistics)
- B.Sc. (University of Bristol, Mathematics with Computer Science)
- American Association of Cancer Research
- Society of Melanoma Research
- International Genetic Epidemiology Society
Research groups and institutes
- Leeds Institute of Medical Research at St James's
- Epidemiology and Biostatistics
- Immunity and inflammation