CHEK2 Gene Mutation Indicates Breast Cancer Risk in Family Members

CHEK2 Gene Mutation Indicates Breast Cancer Risk in Family Members

First-degree relatives of women with a CHEK2 gene mutation and bilateral breast cancer have a high lifetime risk of developing breast cancer themselves, according to a study published in Lancet .

While BRCA1 or BRCA2 mutations are implicated in certain cases of familial cancers, they do not explain all such cases. In order to further understand familial breast cancer, researchers are evaluating other inherited genetic mutations that increase the risk of cancer. Mutations in the CHEK2 gene appear to be important.

The CHEK2 gene is believed to play a role in controlling the growth of cells. A particular mutation in the CHEK2 gene, known as 1100delC, inactivates the CHEK2 gene and appears to increase the risk of cancer. This gene mutation is present in an estimated 0.5% to 1.3% of white northern Europeans.

Researchers in the UK conducted a study to assess the risk of breast cancer in family members of women with bilateral breast cancer and the 1100delC mutation of the CHEK2 gene. Four hundred and sixty-nine women with bilateral breast cancer were identified from cancer registries, and seven of these women (1.5%) tested positive for the 1100delC mutation.

Risk of breast cancer was elevated in all first-degree relatives of women with bilateral breast cancer, but risk was greatest if a CHEK2 gene mutation was present.

When the woman with bilateral breast cancer had a CHEK2 mutation, her female first-degree relatives had a risk of breast cancer that was roughly 12-times higher than that of the general population. By the age of 80, 59% of these female relatives were expected to develop breast cancer. Because of the small number study participants with a CHEK2 mutation, it was not possible to estimate risk of breast cancer in male family members.

In contrast, when the woman with bilateral breast cancer did not have a CHEK2 mutation, her female first-degree relatives had a risk of breast cancer that was roughly three-and-one-half-times higher than that of the general population. By the age of 80, 24% of these female relatives were expected to develop breast cancer. Male first-degree relatives also had an increased risk of developing breast cancer.

These results suggest that first-degree relatives of women with bilateral breast cancer have an increased risk of developing breast cancer themselves; the risk is greatest if a CHEK2 gene mutation is present. The researchers note that testing women with a family history of bilateral breast cancer for the 1100delC mutation of the CHEK2 gene may provide important information about their lifetime risk of breast cancer.

Reference: Johnson N, Fletcher O, Naceur-Lombardelli C et al. Interaction Between CHEK2*1100delC and Other Low-Penetrance Breast-Cancer Susceptibility Genes: A Familial Study. Lancet. 2004;366:1554-57.

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