Endocrine Abstracts

CHEK2, located on chromosome 22q, is a tumor suppressor gene. Its’ pathogenic variants are often associated with a tumor predisposition syndrome 4, with an increased risk of breast, prostate and colorectal cancers. There are some reports of an increased risk of papillary thyroid cancer (PTC) in carriers of the CHEK2 pathogenic variants. Current guidelines, however, do not recommend general screening of TC patients. The study assessed the prevalence of pathogenic CHEK2 variants in patients diagnosed with TC with a personal and/or familial history of other malignancies. The study was a retrospective analysis of a group of 163 patients (138 females and 25 males, mean age of 48.9 years) diagnosed with TC and with a positive personal and/or familial history of other mutation-related malignancies. CHEK2 (exons 4, 5, 12) were analyzed by Sanger sequencing. If negative – deletions analysis was performed with MLPA. Pathogenic or likely pathogenic CHEK2 variants were found in 25 patients (21 females and four males; 15, 3% of the study group). There was no significant difference in the mean age at diagnosis in patients positive and negative for CHEK2 pathogenic variants (46 vs 49 years, respectively; P=0.39). The average number of malignancies in the family members was higher in patients harboring CHEK2 pathogenic variants; the difference was not statistically significant (1.88 vs 1.63; P= 0.36). There was no difference in the personal history (12% vs 29.7%, respectively) or family history (84% vs 83%, respectively) of other malignancies in CHEK2- positive and negative PT cancers. There was no significant difference between CHEK2 positive and negative patients in number of breast, prostate and colon cancers combined in family members. Thyroid cancer was significantly more common in family members of patients with CHEK2 pathogenic variants (9 cases vs 12 cases in CHEK2 negative group, P= 0.006).

Conclusions: The frequency of CHEK2 pathogenic variants in a preselected group of PT patients with a personal and/or familial history of other malignancies is similar to that previously reported in the unselected group of Polish patients with PTC. There is currently no convincing data justifying the selective screening for CHEK2 in such a group. It seems reasonable to advise genetic testing for CHEK2 pathogenic variants in TC patients with positive family history of thyroid cancer.