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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. The PALB2 gene encodes the protein PALB2, which stands for 'partner and localiser of BRCA2'.
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. PALB2 and breast cancerThe 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. News: CHEK2 gene increases risk of breast cancer (17/05/04) 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. Adapted from a news release by The Institute of Cancer Research. Further readingRahman N et al. PALB2, which encodes a BRCA2-interacting protein, is a breast cancer susceptibility gene. Nat Genet 2007;39(2):165-7. Abstract Reid S et al. Biallelic mutations in PALB2 cause Fanconi anemia subtype FA-N and predispose to childhood cancer. Nat Genet 2007;39(2):162-4. Abstract |
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