Haplotypes of the I157T CHEK2 germline mutation in ethnically diverse populations

Bella Kaufman, Yael Laitman, Jacek Gronwald, Robert Winqvist, Arvids Irmejs, Jan Lubinski, Katri Pylkäs, Janis Gardovskis, Edvins Miklasevics, Eitan Friedman

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)


The CHEK2 I157T missense mutation, reported in ethnically diverse, high-risk families, moderately increases breast and colon cancer risk. The present study assessed whether this mutation represents a founder mutation. Participants identified in high risk clinics or from consecutive cancer patients in Israel, Poland, Latvia, and Finland, were either carriers of the CHEK2 I157T mutation or non-carrier family members. Multi-locus genotyping employed two intragenic markers and five CHEK2 gene flanking markers, spanning about 645 kb. Haplotyping was done when families were available for phasing. Overall, 101 individuals (83 I157T CHEK2 mutation carriers) were genotyped: 16 Finnish individuals from 11 families (14 mutation carriers, two non-carrier family members), 50 Polish individuals (20 families) (35 carriers, 15 non-carriers), 28 unrelated Latvian mutation carriers, and seven Israeli participants (two families) (six mutation carriers, one non-carrier). Overall 36/83 mutation carriers (43%) were diagnosed with breast cancer, 15/83 (18%)-colon cancer, three-ovarian cancer, one-thyroid cancer, and the rest (n = 28) were asymptomatic. A common core haplotype was detected in all I157T CHEK2 mutation carriers of Israeli, Polish, and Finnish origin between markers D22S275-D22S689 (~258 kb), with a different allele pattern in Latvians. In conclusion, CHEK2 I157T missense mutation is a founder mutation in ethnically diverse populations, but may also be a mutational hotspot.

Original languageEnglish
Pages (from-to)473-478
Number of pages6
JournalFamilial Cancer
Issue number4
Publication statusPublished - Dec 2009


  • CHEK2 gene
  • Founder mutation
  • Germline mutations
  • Haplotype
  • High risk cancer families

Field of Science*

  • 3.1 Basic medicine
  • 3.2 Clinical medicine

Publication Type*

  • 1.1. Scientific article indexed in Web of Science and/or Scopus database


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