Scientists in major prostate cancer gene discovery

Cancer Research UK

SCIENTISTS have discovered nine new sites in the human genome that have variants that can increase a man's risk of developing prostate cancer by three fold. Their findings are published in two papers in Nature Genetics* today (Sunday).

In the first study, an international team of scientists led by Cancer Research UK funded researchers at The Institute of Cancer Research (ICR) and the University of Cambridge analysed variations in the genomes of almost 38,000 men and found seven regions in the genome that increase the risk of developing prostate cancer. They are located at sites on chromosomes 2, 4, 8, 11 and 22.

One of the genes, NKX3.1, could be a useful as a new target for treating prostate cancer. It helps control how cells die and when damaged can be a key element in developing cancer.

Drugs called HDAC1 inhibitors, that play a similar role to this gene, are currently in clinical trials and this research could help doctors target this treatment to men with variations in the NKX3.1 gene.

Another gene, ITGA6, could also be a potential target for new drugs. It plays an important role in cell growth, movement and survival and when overactive it is associated with some prostate cancers.

Lead author Dr Ros Eeles, from the ICR, said: "Our study adds further compelling evidence that genetic factors can influence a man's risk of developing prostate cancer. These results will help us to more accurately calculate the risk that a man could develop prostate cancer which will enable more targeted screening. Understanding more about these genes could also lead to the development of new treatments."

The team examined the genetic differences in 19,879 men with prostate cancer and 18,761 healthy individuals - using data from 21 studies worldwide. This looked at differences in over 43,000 SNPs, pieces of DNA that vary between individuals. The team identified seven regions that were all linked to a man’s risk of developing prostate cancer.

This research takes the total number of regions of the human genome associated with an increased prostate cancer risk to over 20.

In the second paper, the scientists studied a region on chromosome 8 which has previously been identified as having an important link to prostate cancer risk. They found two new SNPs that each, independently, affect the risk of developing prostate cancer, bringing the total number in this region to eight.

Based on all the studies to date, the scientists estimate that one in 100 men carry most of the genetic variants and their lifetime risk of developing prostate cancer is one in five compared with the average of one in ten.

Joint lead author, Professor Doug Easton, director of Cancer Research UK's Genetic Epidemiology Unit at the University of Cambridge added: "Prostate cancer has the greatest number of independent genes affecting risk of any cancer but we still understand very little about how it develops. This study provides new clues about the processes involved, which could be used to aid the development of new treatments in the future."

Prostate cancer is the most common cancer in men in the UK. A quarter of all new cases of cancer diagnosed in men are prostate cancers. In 2006, more than 35,000 men in the UK were diagnosed with the disease. Around seven in ten newly diagnosed prostate cancer patients now survive beyond five years. In the 1970s, when the numbers of men detected with slow growing prostate cancers were lower, it was three in ten. Each year around 10,200 men in the UK die from prostate cancer.

Harpal Kumar, chief executive of Cancer Research UK, said: "This important research increases our knowledge of how some genes can affect men's risk of developing prostate cancer. Thanks to international collaborations like this, funded by Cancer Research UK and others, we have been able to scan the DNA of thousands of men to discover more about the genes that affect prostate cancer risk. This is ground-breaking research that we hope will open up more avenues worldwide to diagnose, prevent and treat this disease better."

For media enquiries please contact the Cancer Research UK press office on 020 7061 8300 or, out-of-hours, the duty press officer on 07050 264 059.

References

Eeles, R et al. (2009). Identification of seven new prostate cancer susceptibility loci through a genome-wide association study Nature Genetics, 41 (10), 1116-1121 DOI: 10.1038/ng.450

Al Olama AA, et al (2009). Multiple loci on 8q24 associated with prostate cancer susceptibility. Nature genetics, 41 (10), 1058-60 PMID: 19767752

Notes to Editor

This research will also be presented at the NCRI Cancer Conference on Tuesday 6 October. Find out more about the 2009 NCRI Cancer Conference

Family history and prostate cancer risk

A family history of prostate cancer is one of the strongest known risk factors for this disease. It has been estimated that 5-10 per cent of all prostate cancer cases and 30-40 per cent of early-onset cases (men diagnosed under the age of 55 years) are caused by inherited susceptibility genes.

Risk increases two to three times for men with a first-degree relative diagnosed with prostate cancer. If the relative is less than 60 years old at diagnosis or more than one relative is affected (at any age), the individual's risk is four times the average. These factors combine so that if more than one relative is affected by early-onset prostate cancer, the risk is increased by seven-fold.

A strong family history of breast cancer may also affect a man's risk of prostate cancer, particularly if the family members were diagnosed under the age of 60. In particular, germline mutations in the breast cancer susceptibility genes, BRCA1 and BRCA2, can predispose men to prostate cancer.

Recently, genome-wide association studies have identified several genetic variants that each slightly increase prostate cancer risk. However, because such genetic variants are common in the population, they may contribute to a significant proportion of all prostate cancer cases. Current research in this area is likely to identify further variants in the next few years. Genetic profiling is being used to inform prostate screening and treatment.