Absence of CHEK2 1100delC mutation in familial breast cancer cases from a South American population

Excerpt

The most widely accepted model proposes that familial breast cancer susceptibility is a consequence of a small number of mutations in BRCA1 or BRCA2 (BRCA1/2) and a much higher proportion of mutations in ethnic-specific genes of moderate and/or low penetrance [1]. CHEK2 gene, involved in DNA damage and replication checkpoints, has been pointed out as a good candidate. Moreover, a specific variant in this gene, 1100delC, has been found to increase breast cancer susceptibility among familial breast cancer cases not attributable to mutations in BRCA1/2 [2]. Most of the studies evaluating this mutation as a female breast cancer susceptibility allele have been conducted in European populations, where the prevalence of the variant in controls ranged from 0 out of 400 controls in Spain to 2.8% in the Netherlands (Table 1). This variant has been detected in a considerable higher proportion (4–11%) in patients with a positive family history of breast cancer (usually known to be BRCA1/2 mutation-negative) from Northern Europe (Table 1) This variant has been estimated to be associated with an approximately 1.5–2.0 fold increased risk in female breast cancer cases with a positive family history [4‐6]. CHEK2 has not been well studied in other ethnic groups. …