Genetic variation and cancer risk
About Paul Pharoah
Professor Paul Pharoah works at the University of Cambridge, studying how a person's genes, lifestyle and environment interact to determine their cancer risk. In particular, Professor Pharoah is hoping to identify small genetic differences that may affect a person's risk of breast cancer or how they will respond to treatment. He is also investigating the genes and risk factors involved in ovarian cancer.
Scientists have already found several 'high-risk' genes. For example, mutations in a woman's BRCA1 or BRCA2 genes can greatly increase her risk of breast and ovarian cancers. But these only account for a small proportion of cases.
As well as these rare 'high-risk' genes, scientists have found evidence that a person's cancer risk is also affected by the combined effect of subtle variations in many other genes. These gene variants are often called 'low-risk' or 'low-penetrance' genes.
By identifying these gene variations, it may be possible to assess a person's cancer risk more accurately. People at increased risk could then be offered advice, screening or other treatments to lower their chances of developing the disease.
Breast cancer genetics
Around 7,000 breast cancer patients in East Anglia are taking part in Professor Pharoah's study. By comparing their genetic makeup with that of unaffected people, the team hopes to identify certain gene combinations that increase a woman's risk.
These women could be offered specialist advice and be asked to attend regular screening to detect the disease at an early stage. In 2007, Professor Pharoah helped identify five new genetic regions that slightly increase a woman's risk of breast cancer.
As well as of influencing a person's risk of developing cancer, gene variants may affect the way people respond to cancer treatments.
In future, it may be possible to tailor treatment according to precisely which gene variations a person carries.
Ovarian cancer genetics
Professor Pharoah is also involved in work aimed at identifying women at increased risk of ovarian cancer. He runs the Familial Ovarian Cancer Registry (FOCR), a database of over 400 families with a strong history of ovarian cancer.
This registry is being analysed to see if any common genes and other risk factors can be found. In future, this information will be invaluable to doctors, helping them to provide accurate, tailored advice to people with a family history of the disease. The FOCR is thought to be the largest well-documented set of ovarian cancer families in the world.
Other research projects by Paul Pharoah
Funding period: 01 October 2008 to 30 September 2013
The Golestan Cohort Study follow-up: An investigation of environmental and genetic risk factors for esophageal cancer in north-east Iran
Funding period: 01 June 2009 to 31 May 2014
Vitamin D receptor rs2228570 polymorphism and invasive ovarian carcinoma risk: pooled analysis in five studies within the Ovarian Cancer Association Consortium
Int J Cancer.2011;128 :936-943
Endometrial cancer and genetic variation in PTEN, PIK3CA, AKT1, MLH1, and MSH2 within a population-based case-control study
Gynecol Oncol.2011;120 :167-173