The CHEK2 1100delC mutation is not present in Korean patients with breast cancer cases tested for BRCA1 and BRCA2 mutation

Abstract

The germline CHEK2 1100delC mutation is a low penetrance breast cancer susceptibility allele, frequently observed in patient with family history of breast cancer and/or young age and the frequency varied according to race or ethnicity. In this study, we evaluated the significance of CHEK2 1100delC in predisposition to breast cancer by assessing its frequency in a material of 493 Korean breast cancer patients who had been screened for BRCA1 and BRCA2 mutations (42 patients had deleterious mutation of BRCA1/2). Mutation detection of CHEK2 1100delC was based upon analysis of primer extension products generated for previously amplified genomic DNA using a chip based MALDI-TOP mass spectrometry platform. After overall measurement automatically, assays which had bad peaks were checked again manually. None of the 493 Korean patients with breast cancer who were candidate for BRCA1 and BRCA2 test carried the 1100delC mutation observed in Caucasians with limited frequency. In the previous studies, we observed higher or comparable prevalence of BRCA1 and BRCA2 mutations in Korean patients with breast cancer compared to Caucasian breast cancer population. In the present study, we evaluated the role of a CHEK2 1100delC as a susceptibility mutation of breast cancer in the Korean population. However, our results suggest that this mutation is absent or may be very infrequent in Korean patients with breast cancer who have high risk of BRCA1 and BRCA2 mutation, making its screening irrelevant from the practical point view.

CHEK2 1100delC Variant and Breast Cancer Risk in Caucasians: A Meta-analysis Based on 25 Studies with 29,154 Cases and 37,064 Controls

“…Because the results in those two countries showed that no target variant was found in the cases and controls. Similar results were found for the CHEK2 gene in other studies conducted using Asian populations (Rajkumar et al, 2003;Song et al, 2006;Choi, 2008;Bell et al, 2007;Lee and Ang, 2008;Thirthagiri et al, 2009). Therefore, we excluded these studies in our metaanalysis.…”

“…It also occurs at a very low frequency in familial breast cancer patients (1.50%). Furthermore, it is rarely found in Asians (Rajkumar et al, 2003;Song et al, 2006;Bell et al, 2007;Choi, 2008;Lee and Ang, 2008;Thirthagiri et al, 2009). Secondly, in the previous meta-analysis, the cumulative risk of breast cancer at 70 years of age was calculated based on another meta-analysis done in 2007, which estimated the cumulative risk of two other gene heterozygotes, BRCA1 and BRCA2 (Chen and Parmigiani, 2007).…”

“…Reviews, editorials, meeting abstracts, and commentaries were excluded from our analysis. We also excluded studies that did not detect the CHEK2 1100delC allele in both cases and controls (Rajkumar et al, 2003;Song et al, 2006;Bell et al, 2007;Choi, 2008;Lee and Ang, 2008;Thirthagiri et al, 2009). …”

“…However, this widely discussed variant of CHEK2 -which seemed clearly associated with the predominance of breast cancer in western countries -was rarely detected in Asian populations, such as the Chinese (Song et al, 2006), Koreans (Choi, 2008), Japanese (Bell et al, 2007), Singaporeans (Lee and Ang, 2008), Malaysians (Thirthagiri et al, 2009) and South Indians (Rajkumar et al, 2003). With the influx of recent studies concerning these particular findings, a stricter meta-analysis with the recent data is necessary.…”

PALB2 mutations 1592delT and 229delT are not present in Korean breast cancer patients negative for BRCA1 and BRCA2 mutations

“…Three-hundred patients were confirmed free of mutations in BRCA1 and BRCA2 and constituted the subjects of the study. The study was originally approved by each institutional review board and informed consent for genetic testing of breast cancer was obtained from all the subjects, as described in previous study [23]. The mean age was 41 years (SD 9.7 years).…”