Recent reports have implicated the cell-cycle-checkpoint kinase CHEK2 gene in the susceptibility to breast and other cancers. Among all gene sequence alterations reported thus far, the truncating c.1100delC mutation, commonly referred to as 1100delC, appears to be the most relevant for breast cancer predisposition. In order to evaluate the prevalence and significance of this mutation in Italy, we performed a multicenter study with a total of 1,273 subjects, including unrelated breast cancer patients and unaffected individuals representative of the Italian population. While 1100delC has recently been proven to be associated with an increased risk of breast cancer by more than one study, the identification of this mutation in only 1 out of 939 (0.11%, 95% CI = 0.00–0.59%) unrelated patients from Italian breast cancer families, indicates that it is of little consequence to breast cancer predisposition in the Italian population. Notably, this frequency is significantly lower than that observed in breast cancer families of northern Europe (P o 0.0001, Fisher’s exact test). Evidence for a common founder of Northern European 1100delC carriers was obtained in a previous study and may explain the observed frequency variation among different European populations. Lower than expected frequencies were also reported by a recent study that identified the mutation in 1% of selected New York breast cancer patients. Thus, the relevance of 1100delC mutation in breast cancer predisposition remains limited to specific populations, possibly of Northern European origin.
The CHEK2 c.1100delC mutation plays an irrelevant role in breast cancer predisposition in Italy
ACETO, Gitana;VESCHI, SERENA;CAMA, Alessandro;
2004-01-01
Abstract
Recent reports have implicated the cell-cycle-checkpoint kinase CHEK2 gene in the susceptibility to breast and other cancers. Among all gene sequence alterations reported thus far, the truncating c.1100delC mutation, commonly referred to as 1100delC, appears to be the most relevant for breast cancer predisposition. In order to evaluate the prevalence and significance of this mutation in Italy, we performed a multicenter study with a total of 1,273 subjects, including unrelated breast cancer patients and unaffected individuals representative of the Italian population. While 1100delC has recently been proven to be associated with an increased risk of breast cancer by more than one study, the identification of this mutation in only 1 out of 939 (0.11%, 95% CI = 0.00–0.59%) unrelated patients from Italian breast cancer families, indicates that it is of little consequence to breast cancer predisposition in the Italian population. Notably, this frequency is significantly lower than that observed in breast cancer families of northern Europe (P o 0.0001, Fisher’s exact test). Evidence for a common founder of Northern European 1100delC carriers was obtained in a previous study and may explain the observed frequency variation among different European populations. Lower than expected frequencies were also reported by a recent study that identified the mutation in 1% of selected New York breast cancer patients. Thus, the relevance of 1100delC mutation in breast cancer predisposition remains limited to specific populations, possibly of Northern European origin.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
