CHEK2 1100delC mutation is frequent among Russian breast cancer patients

Chekmariova, Elena V.; Sokolenko, Anna P.; Buslov, Konstantin G.; Iyevleva, Aglaya G.; Ulibina, Yulia M.; Rozanov, Maxim E.; Mitiushkina, Natalia V.; Togo, Alexandr V.; Matsko, Dmitry E.; Voskresenskiy, Dmitry A.; Chagunava, Oleg L.; Devilee, Peter; Cornelisse, Cees J.; Семиглазов, Владимир; Imyanitov, Evgeny N.

doi:10.1007/s10549-006-9227-7

Cited by 36 publications

(23 citation statements)

References 16 publications

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“…Several studies have shown higher frequencies (ranging from 1.7 to 14.3%) of mutation among women with bilateral breast cancer (Oldenburg et al, 2003;Broeks et al, 2004;Kilpivaara et al, 2005;Chekmariova et al, 2006;Kwiatkowska et al, 2006); however, none of these were population-based. Two of these studies reported that the frequency of mutation was significantly increased among women with bilateral breast cancer compared to women with UBC (Broeks et al, 2004;Kilpivaara et al, 2005).…”

Section: Discussionmentioning

confidence: 99%

Risk for contralateral breast cancer among carriers of the CHEK2*1100delC mutation in the WECARE Study

et al. 2008

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The protein encoded by the CHEK2 gene is involved in cellular repair of DNA damage. The truncating mutation, CHEK2*1100delC, seems to increase the risk for breast cancer. We investigated whether the CHEK2*1100delC mutation carrier status increases the risk for asynchronous contralateral breast cancer (CBC) and whether it interacts with radiation therapy (RT) or chemotherapy in regard to CBC risk. The germline mutation frequency was assessed in 708 women with CBC and 1395 women with unilateral breast cancer (UBC) in the Women's Environment, Cancer and Radiation Epidemiology (WECARE) Study whose first primary breast cancer was diagnosed before age 55 years and during 1985 -1999. Seven women with CBC (1.0%) and 10 women with UBC (0.7%) were CHEK2*1100delC variant carriers (rate ratio (RR) ¼ 1.8, 95% confidence interval (CI) ¼ 0.6 -5.4 for CBC vs UBC). Carriers who received RT for their first breast cancer, compared with non-carriers not treated with RT, had an RR of developing CBC of 2.6 (95% CI ¼ 0.8 -8.7). We found no significant associations between the CHEK2*1100delC mutation and CBC overall or among those treated with RT. However, the sampling variability was such that modest increases in risk could not be excluded. Nonetheless, because this is a rare mutation, it is unlikely to explain a major fraction of CBC in the population.

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Section: Discussionmentioning

confidence: 99%

Risk for contralateral breast cancer among carriers of the CHEK2*1100delC mutation in the WECARE Study

et al. 2008

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“…The results of breast cancer studies led to the identification of several predominant founder mutations within the CHEK2 gene and suggested that these mutations were unevenly distributed within the world populations. The c.1100delC mutation most frequently studied in CHEK2 that leads to translation of truncated protein lacking kinase domain, is highly incident in Northern and Western Europe [13] and in Russia [14] but its occurrence in Southern Europe [15,16], South America [17] or China [18] is very low. Similar differences in distribution were also found in other CHEK2 frequently analyzed mutations located within its FHA domain-c.470T [ C (I157T) and IVS2 + 1G [ A (fs154X) [19].…”

Section: Introductionmentioning

confidence: 99%

Analysis of CHEK2 FHA domain in Czech patients with sporadic breast cancer revealed distinct rare genetic alterations

Kleibl

Havránek

Novotný

et al. 2007

Breast Cancer Res Treat

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The CHEK2 gene mutations I157T (c.470T>C) and IVS2+1G>A affecting the forkhead-associated domain (FHA) have been shown to increase the risk of breast cancer development in several populations. We analyzed the CHEK2 gene segment coding for FHA domain in 673 unselected breast cancer patients and 683 controls from the Czech Republic using the denaturant high-performance liquid chromatography. The found frequency of predominant FHA alteration I157T did not differ between breast cancer patients (19/673; 2.82%) and controls (17/683; 2.49%; P=0.71). Besides this mutation we characterized another nine alterations-six located within FHA coding sequence and three occurring in introns 1 or 2). Eight variants occurred once each in patients with breast cancer and two were present in controls. Three alterations found in breast cancer patients were novel missense variants (Y159H, T172A, and L174F) affecting highly conservative residues in FHA domain. Despite the lack of association of I157T mutation with breast cancer development in our population we deduced that the FHA domain is the subject of rare population-specific alterations that might modify risk of various cancers.

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“…Petrov Institute of Oncology (St.-Petersburg) within years [10][11][12][13]. In addition, we considered previously obtained results of the analysis of entire BRCA1-coding region [14].…”

Section: Methodsmentioning

confidence: 99%

Breast cancer sensitivity to neoadjuvant therapy in BRCA1 and CHEK2 mutation carriers and non-carriers

Pfeifer

Sokolenko

Potapova

et al. 2014

Breast Cancer Res Treat

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Breast carcinomas caused by inheritance of cancer-predisposing germ-line mutations have specific bioclinical features. This study aimed to analyze the efficacy of conventional cytotoxic treatment in BRCA1 and CHEK2 mutation carriers and non-carriers. The study included 415 Russian breast cancer patients aged 50 years or younger, who were subjected to various standard schemes of neoadjuvant therapy. The choice of therapy was done without the knowledge of the mutations status, because DNA testing was performed retrospectively using the archival tissue samples. 19 BRCA1 (4.6%) and 8 CHEK2 (1.9%) heterozygous genotypes were identified. BRCA1 mutation carriers achieved pathological complete response more frequently than non-carriers [6/19 (31.6%) vs. 46/388 (11.9%), p = 0.024]; this effect was limited to women treated by anthracycline-based therapy without taxanes [5/9 (55.6%) vs. 28/247 (11.3%), p = 0.002] and was not observed in any of 7 BRCA1 carriers receiving taxane-containing regimens. CHEK2 heterozygotes did not experience pathological complete response and showed lower frequency of objective clinical responses as compared to mutation non-carriers [4/8 (50%) vs. 333/388 (85.5%), p = 0.020]; the efficacy of neoadjuvant therapy was particularly poor in CHEK2 carriers receiving anthracyclines without taxanes. This study provides evidence for distinct sensitivity of BRCA1 and CHEK2 mutation-driven breast carcinomas to standard chemotherapeutic schemes.

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CHEK2 1100delC mutation is frequent among Russian breast cancer patients

Cited by 36 publications

References 16 publications

Risk for contralateral breast cancer among carriers of the CHEK2*1100delC mutation in the WECARE Study

Risk for contralateral breast cancer among carriers of the CHEK2*1100delC mutation in the WECARE Study

Analysis of CHEK2 FHA domain in Czech patients with sporadic breast cancer revealed distinct rare genetic alterations

Breast cancer sensitivity to neoadjuvant therapy in BRCA1 and CHEK2 mutation carriers and non-carriers

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