HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

CHEK2 mutations and the risk of papillary thyroid cancer.

Abstract
Mutations in the cell cycle checkpoint kinase 2 (CHEK2) tumor suppressor gene are associated with multi-organ cancer susceptibility including cancers of the breast and prostate. A genetic association between thyroid and breast cancer has been suggested, however little is known about the determinants of this association. To characterize the association of CHEK2 mutations with thyroid cancer, we genotyped 468 unselected patients with papillary thyroid cancer and 468 (matched) cancer-free controls for four founder mutations of CHEK2 (1100delC, IVS2 + 1G>A, del5395 and I157T). We compared the family histories reported by patients with a CHEK2 mutation to those of non-carriers. A CHEK2 mutation was seen in 73 of 468 (15.6%) unselected patients with papillary thyroid cancer, compared to 28 of 460 (6.0%) age- and sex-matched controls (OR 3.3; p < 0.0001). A truncating mutation (IVS2 + 1G>A, 1100delC or del5395) was associated with a higher risk of thyroid cancer (OR = 5.7; p = 0.006), than was the missense mutation I157T (OR = 2.8; p = 0.0001). CHEK2 mutation carriers reported a family history of breast cancer 2.2 times more commonly than non-carriers (16.4% vs.8.1%; p = 0.05). A CHEK2 mutation was found in seven of 11 women (63%) with multiple primary cancers of the breast and thyroid (OR = 10; p = 0.0004). These results suggest that CHEK2 mutations predispose to thyroid cancer, familial aggregations of breast and thyroid cancer and to double primary cancers of the breast and thyroid.
AuthorsMonika Siołek, Cezary Cybulski, Danuta Gąsior-Perczak, Artur Kowalik, Beata Kozak-Klonowska, Aldona Kowalska, Małgorzata Chłopek, Wojciech Kluźniak, Dominika Wokołorczyk, Iwona Pałyga, Agnieszka Walczyk, Katarzyna Lizis-Kolus, Ping Sun, Jan Lubiński, Steven A Narod, Stanisław Góźdż
JournalInternational journal of cancer (Int J Cancer) Vol. 137 Issue 3 Pg. 548-52 (Aug 01 2015) ISSN: 1097-0215 [Electronic] United States
PMID25583358 (Publication Type: Journal Article)
Copyright© 2015 UICC.
Chemical References
  • Checkpoint Kinase 2
Topics
  • Adolescent
  • Adult
  • Aged
  • Carcinoma (diagnosis, epidemiology, genetics)
  • Carcinoma, Papillary
  • Case-Control Studies
  • Checkpoint Kinase 2 (genetics)
  • Female
  • Genetic Predisposition to Disease
  • Genotype
  • Heterozygote
  • Humans
  • Male
  • Middle Aged
  • Mutation
  • Neoplasm Metastasis
  • Neoplasm Staging
  • Neoplasms, Second Primary (epidemiology, genetics)
  • Odds Ratio
  • Risk
  • Thyroid Cancer, Papillary
  • Thyroid Neoplasms (diagnosis, epidemiology, genetics)
  • Young Adult

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: