Association of recurrent mutations in BRCA1, BRCA2, RAD51C, PALB2, and CHEK2 with the risk of borderline ovarian tumor

Abstract

Background There are several genes associated with ovarian cancer risk. Molecular changes in borderline ovarian tumor (BOT) indicate linkage of this disease to type I ovarian tumors (low-grade ovarian carcinomas). This study determined the prevalence and association of mutations in BRCA1, BRCA2, PALB2, RAD51C, and CHEK2 with the risk of BOTs. Methods The study group consisted of 102 patients with histologically confirmed BOT and 1743 healthy controls. In addition, 167 cases with ovarian cancer G1 were analyzed. The analyses included genotyping of 21 founder and recurrent mutations localized in 5 genes (BRCA1, BRCA2, PALB2, RAD51C, and CHEK2). The risk for developing BOT and low-grade ovarian cancer, as well as the association of tested mutations with survival, was estimated. Results The CHEK2 missense mutation (c.470T>C) was associated with 2-times increased risk of BOT (OR=2.05, p=0.03), at an earlier age at diagnosis and about 10% worse rate of a 10-year survival. Mutations in BRCA1 and PALB2 were associated with a high risk of ovarian cancer G1 (OR=8.53, p=0.005 and OR=7.03, p=0.03, respectively) and were related to worse all-cause survival for BRCA1 carriers (HR=4.73, 95%CI 1.45–15.43, p=0.01). Conclusions Results suggest that CHEK2 (c.470T>C) may possibly play a role in the pathogenesis of BOT, but due to the low number of BOT patients, obtained results should be considered as preliminary. Larger more in-depth studies are required.

Do survivors of borderline ovarian tumors have susceptibility to secondary primary malignancies? A SEER population‐based study

“…The mutation profiles in BOT were more dissimilar compared with ovarian cancer. A germline mutation of BRCA1 or BRCA2 was rarely found in patients with BOT, 20–22 but a missense mutation (c.470T>C) in the CHEK2 gene was found in 10.8% of BOT patients 20 . Although CHEK2 germline mutations were reported in patients with hereditary breast, prostate, kidney, thyroid, and colon cancers, 23 no cases of a second primary tumors have been reported in CHEK2 mutation carriers with BOT.…”

“…A germline mutation of BRCA1 or BRCA2 was rarely found in patients with BOT, [20][21][22] but a missense mutation (c.470T>C) in the CHEK2 gene was found in 10.8% of BOT patients. 20 Although CHEK2 germline mutations were reported in patients with hereditary breast, prostate, kidney, thyroid, and colon cancers, 23 no cases of a second primary tumors have been reported in CHEK2 mutation carriers with BOT. Even now, we are faced with challenges in reaching consistent conclusions regarding the types and the risk of SPM.…”

Mutation characteristics of cancer susceptibility genes in Chinese ovarian cancer patients

“…However, there are few studies on the association of CHEK2 mutations and age at the onset of ovarian cancer. A study ( 47 ) in Poland containing 2012 ovarian cancer patients showed that the average age of the ovarian cancer group with CHEK2 was 38 years, while the average age of the CHEK2 -negative ovarian cancer group was 49 years.…”

Molecular Landscape of Borderline Ovarian Tumors: A Systematic Review

“…Furthermore, available evidence points to the potential involvement of CHEK2 mutations in BOTs. One study demonstrated that patients with BOTs carried a common missense mutation (c.470T>C) within the CHEK2 gene [54]. The role of that mutation was further analyzed in patients with ovarian cystadenomas, BOTs, and ovarian cancers.…”

“…Furthermore, available evidence suggests that the CHEK2 missense mutation might be associated with a two-fold increase in BOT risk. Additionally, a link has been found between the presence of the CHEK2 missense mutation (c.470T>C) and an earlier age at the diagnosis of BOT [54]. While overall survival rates in BOT patients are generally more favorable than in those with ovarian cancer, the 10-year survival rates in the mutation carriers were shown to be approximately 10% lower than in non-carriers.…”