Women who inherit one damaged copy of a gene called PALB2 have double the risk of developing breast cancer. And children who inherit two damaged copies have a newly identified serious disorder linked to childhood tumours, according to the findings from two papers published by scientists in Nature Genetics* today (Sunday).

A Cancer Research UK funded team at The Institute of Cancer Research looked for faults in the PALB2 gene in 923 women with breast cancer and a family history of the disease, not caused by the known breast cancer genes BRCA1 or BRCA2. The team also looked for faults in the PALB2 gene in 1084 healthy control women. Their discovery could eventually help identify women at greater risk of developing breast cancer. Understanding more about the specific genetic faults that lead to the disease will hopefully help with improving prevention, diagnosis and “tailor-made” treatment in the future.

The team found faults in ten breast cancer patients and no faults in the healthy women. This difference, which is bigger than would be expected by chance, indicates the gene is linked to some cases of breast cancer. The findings show that carrying a faulty version of PALB2 more than doubles a woman’s risk of developing breast cancer – taking her lifetime risk from one in nine to around one in five.

Professor Nazneen Rahman from The Institute of Cancer Research, who led both studies, said: “We estimate that faults in the PALB2 gene contribute to around 100 cases of breast cancer in the UK each year. Interestingly, one of the ten breast cancer cases we identified as being linked to PALB2 was a male breast cancer, which may mean faults in the PALB2 gene are associated with a higher risk of male breast cancer, but we need to investigate this link further before we know for sure.”

In the second study**, the research team associated the PALB2 gene with a new sub-type of the childhood disorder Fanconi anaemia. The researchers studied 82 children with Fanconi anaemia that was not due to any of the 11 genes known to be responsible for this disease. Seven children were identified as belonging to this new sub-type, – which is characterised by a high risk of childhood solid tumours including medulloblastoma, a type of brain tumour, and Wilms’ tumour, a form of kidney cancer. It is when, very rarely, two faults in the PALB2 gene are inherited that this newly identified sub-type of Fanconi anaemia develops.

Professor Rahman added: “Not only have we found that carrying a single faulty version of PALB2 leads to a small increased risk of breast cancer, but also that carrying two faulty copies of the gene is related to an aggressive form of the childhood disorder Fanconi anaemia.”

PALB2 is a DNA-repair gene, so people with a faulty version of this gene cannot repair damaged DNA correctly. Individuals who carry faulty DNA-repair genes are at an increased risk of cancer because their healthy cells are more likely to accumulate genetic damage that can trigger cells to replicate uncontrollably, causing cancer.

Professor John Toy, Cancer Research UK’s medical director, said: “The discovery of another gene that increases breast cancer risk albeit only for a small number of women is very important. Gradually, we are beginning to learn more and more about the rogue genes that cause cancer in some families, and we hope one day to use this knowledge to help those at an increased risk of the disease. All children with Fanconi anaemia are already monitored very closely for signs of cancer, particularly leukaemia. Identifying children with a unique type of this disease, one characterised by a high risk of developing certain solid tumours, is a significant finding that will assist doctors looking after these particular patients in the future.”


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*PALB2, which encodes a BRCA2 interacting protein, is a breast cancer susceptibility gene. Rahman et al. (2006). Nature Genetics

**Biallelic mutations in PALB2, which encodes a BRCA2 interacting protein, cause Fanconi anaemia subtype FA-N and predispose to childhood cancer. Reid et al. (2006). Nature Genetics

The PALB2 gene encodes the protein PALB2, which stands for ‘partner and localizer of BRCA2’.

Breast cancer genes

The relative risk of breast cancer associated with PALB2 mutations was estimated to be 2.3 (two-fold). This is similar to the increase in risk seen with the CHEK2, ATM and BRIP1 genes – all reported by the same research group since 2002. PALB2 is the first low-risk gene protein product found that interacts with BRCA2 – all of the other low-risk genes, CHEK2, ATM and BRIP1, are linked to BRCA1. Together, these genes are thought to account for around two per cent of all breast cancer cases.

Women who carry a faulty version of one of the well-known breast cancer causing genes, BRCA1 or BRCA2, have a much higher risk of developing the disease – around 80 per cent over their lifetime. Faults in the BRCA1 or BRCA2 genes are thought to account for approximately 5-10 per cent of all breast cancer cases.

Breast cancer is the most common form of cancer in the UK and many women have a family history of the disease. Women with a history of breast cancer in their family have a slightly increased risk of the disease, but most women with one or two affected relatives will not get breast cancer. The risk is greater if a close relative, such as a mother or sister, had breast cancer before the age of 50, or if two or more close relatives have been affected.

Women who have a strong family history of the disease and who are worried about their risk should discuss this with their doctor who may refer them to a breast cancer clinic or a genetics unit. There are several gene faults that can increase breast cancer risk, but at the moment doctors can only test for two of them, BRCA1 and BRCA2, as these are associated with high risks of developing cancer.

Breast cancer statistics

Around 44,000 women are diagnosed each year – equating to 120 women every day. The risk of breast cancer increases with age – four out of five cases occur in after the age of 50. Men can also get breast cancer but it is very rare – around 300 cases each year.

Survival rates for breast cancer have been improving for more than twenty years and more women are being successfully treated than ever before. The estimated five-year survival for women diagnosed is 80 per cent, compared with only 52 per for women diagnosed in the early 1970s. Nowadays, nearly two-thirds of women are surviving breast cancer for twenty years or more, an improvement of 20 per cent over the past decade.

For more information about cancer or cancer treatments visit our patient information website CancerHelp UK

Fanconi Anaemia

Fanconi anaemia (FA) is one of the inherited anaemias that leads to bone marrow failure (aplastic anaemia). It is a recessive disorder: if both parents carry a defect (mutation) in the same FA gene, each of their children has a 25 per cent chance of inheriting the defective gene from both parents. When this happens, the child will have FA. There were previously eleven known FA genes, which account for the great majority of FA cases.

FA occurs equally in males and females and it is found in all ethnic groups. Though considered primarily a blood disease, it can affect all systems of the body. Many patients develop acute myelogenous leukemia (AML) and at a very early age. FA patients also have a high risk of developing head and neck, gynaecological, and/or gastrointestinal squamous cell carcinomas, again at a much earlier age than in patients in the general population. Patients who have had a successful bone marrow transplant and, thus, are cured of the blood problem associated with FA still must have regular examinations to watch for signs of cancer.

The Institute of Cancer Research

The Institute of Cancer Research is Europe’s leading cancer research centre with expert scientists working on cutting edge research. It was founded in 1909 to carry out research into the causes of cancer and to develop new strategies for its prevention, diagnosis, treatment and care. Click here to visit the Institute of Cancer Research’s website.

The Institute works in a unique partnership with The Royal Marsden NHS Foundation Trust, forming the largest Comprehensive Cancer Centre in Europe. This relationship enables close daily contact with those on the frontline in the fight against cancer – the clinicians, the carers and most importantly, the patients.

The Institute is a charity that relies on voluntary income. The Institute is one of the world’s most cost-effective major cancer research organisations with over 90p in every £ directly supporting research.

Cancer Research UK

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