A Comparison between <b><i>CHEK2</i></b>*1100delC/I157T Mutation Carrier and Noncarrier Breast Cancer Patients: A Clinicopathological Analysis

Abstract

Objective: The suppressor gene CHEK2 encodes a cell cycle checkpoint kinase, involved in cell cycle regulation, apoptosis and response to DNA damage. The aim of this study was to analyze the differences between CHEK2 mutation carriers (CHEK2*1100delC/I157T) and noncarriers with respect to clinicopathological factors. Methods: We reviewed the medical records of 100 early breast cancer patients (46 mutation carriers and 54 noncarriers) who were treated with chemotherapy, hormonotherapy or trastuzumab. Results:CHEK2 mutation carriers were older (>65 years) than noncarriers (17 vs. 7%; p = 0.215). Twenty-five (54%) of them had a history of cancer in the family. Gastric cancer in the family history was detected in 11% of mutation carriers and in 2% of noncarriers (p = 0.092). There was a trend for more frequent lymph node metastases in patients without the mutation in comparison to mutation carriers (46 vs. 28%; p = 0.098). Luminal B type breast cancer was detected more often in carriers (39 vs. 20%; p = 0.048). Breast-conserving treatment was also conducted more often in mutation carriers (57 vs. 31%; p = 0.015). Histologic grades G1/G2 were detected more frequently in mutation carriers (82 vs. 70%; p = 0.212). Conclusion: Mutation carriers were characterized by older age, a history of gastric cancer in the family, locally advanced disease, lower histologic grade and luminal B type breast cancer.

Associations of pathogenic mutations responsible for breast cancer risk with histology and immunohistochemistry in Romanian population

“…HER2 was negative in 5 of the 6 cases, this data being in accordance with other studies on patients with CHEK2 mutations and breast cancer (Table 4) [25].…”

Checkpoint Kinase 2 (CHEK2) Mutation in Renal Cell Carcinoma: A Single-Center Experience

“…In some meta-analyses, CHEK2*1100delC heterozygotes have a two-fold risk of malignant melanoma ( 18 ).In addition, Złowocka et al have found that CHEK2 mutations increase the risk of bladder cancer ( 19 ). In our previous study, breast cancer patients with CHEK2 mutation were characterized by older age, history of gastric cancer in family, and lower stage of disease ( 10 ). Pertinent to RCC, a relationship with CHEK2 mutations has been reported previously ( 9 , 25 ).…”

“…CHEK2 mutation has been reported in breast cancer ( 8 – 15 ), colorectal cancer ( 16 , 17 ), malignant melanoma ( 18 ), and bladder cancer ( 17 , 19 ). Especially, the polymorphic variant of CHEK2 gene (1100delC) is associated with increased risk of breast, prostate, colorectal, and thyroid cancers ( 9 , 10 , 20 ), whereas the missense variant I157T, in addition to the above cancers, is known to increase the risk of kidney cancer, ovarian adenocarcinoma, and borderline ovarian cancers ( 16 , 21 ).…”

Molecular characteristics of breast cancer according to clinicopathological factors

“…Treatment strategies are illustrated in Table III. Preliminary results of this study for BRCA, CHEK2 and NOD2 mutations have been presented in our previous publications (16)(17)(18).…”