CHEK2 mutation in renal cell carcinoma (RCC): Single center experience.

480 Background: Renal cell cancer (RCC) accounts for about 4% of all the adult malignancies. RCC occurs in both sporadic and heritable forms. Genetic mutations have been identified as the cause of inherited cancer risk in 1% to 2% of RCC cases overall. In some studies, variant I157T of CHEK2 gene were found to be associated with increased risk of clear cell renal cancer. The aim of this study was to evaluate the association between CHEK2 mutation and RCC in our centre. Methods: We reviewed the medical records of 43 clear cell renal cancer patients (pts) who were diagnosed and treated in COI in Gliwice. Mutation profile was assessed by RFLP-PCR technique. In Poland, there are three polymorphic variants of CHEK2 1100delC, IVS2+1G →A (premature protein truncation), and a common missense variant (I157T) (substitution of an isoleucine for a threonine). We evaluated the presence of CHEK2 mutation in clear cell carcinoma. Results: In our study CHEK2 mutation (variant I157T) was detected in 7% pts. The median age of pts was 57 years (range from 34 to 74). Most of the patients were women (87%). All CHEK2 mutation carriers were women and were >65 years old. Cancer in family history were reported in 80% pts. Most frequently were: breast cancer (33%), gynecological cancers (33%), gastrointestinal cancers (27%), and renal cell carcinoma (20%). There was also described lung cancer in family history (7%). The most frequent cancers in family history in CHEK2 mutation carriers were: breast cancer and gynecological cancers. 20% of pts had other cancers in their history (breast cancer, ovarian cancer, and contralateral renal cell carcinoma). Contralateral renal cell carcinoma was reported in CHEK2 mutation carrier. All pts had nephrectomy due to RCC and all had clear cell renal cancer in histopathologic examination. All CHEK2 mutation carriers had higher grade (grade 3) and capsular invasion. 5% of CHEK2 mutation carriers had TP53 (c.[215G>C])polymorphism. Conclusions: Variant I157T of CHEK2 gene were found to be associated with increased risk of cancer in family history (breast cancer, gynecological cancer), and renal cancer of contralateral kidney. Factors associated with CHEK2 mutation carriers were higher histologic grade (G3) and elderly age.