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Mutation In PALB2 Elevates Risk of Cancer

tive individuals, about one per cent of the studied patients, most of whom turned out to have a familial pattern of disease development. The study also involved 141 unselected male breast cancer patients, 188 familial and 288 unselected colorectal cancers, as well as 164 familial and 475 unselected prostate cancer patients.

In prostate cancer, one multigenerational cancer family was found where cancer occurred in several generations and all patients showed the single mutation in PALB2 that was studied. According to Winqvist, this suggests that this Finnish founder mutation may be important in heritable prostate cancer as well. Male breast cancer and colorectal cancer cases did not display the mutation.

The constitutional mutation elevates the risk of breast cancer four-fold 'Present results show that the discovered PALB2 mutation elevates the risk of breast cancer four-fold. However, we still need more research to better assess the effect on cancer development. As the comprehensive mutation analysis was originally conducted on only 113 cancer families, it may be that there still are other PALB2 genetic defects accounting for heritable breast and prostate cancer susceptibility. Recent results also imply that PALB2 might be a cancer susceptibility gene in other populations as well.

It's been shown that two of the mutations identified in Fanconi anemia patients in non-Finnish populations seem to be associated with familial breast cancer,' says Winqvist. Winqvist points out that, in spite of recent advances, known factors can only explain a fraction of heritable susceptibility to breast cancer. He is nonetheless disposed to believe that the evaluation of yet other biologically significant factors will in time improve the situation. 'Hopefully, increased knowledge of underlying mechanisms will provide better conditions for cancer prevention, diagnostics and treatment,' Winqvist says.



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