GREM1 germline mutation screening in Ashkenazi Jewish patients with familial colorectal cancer

Genet Res (Camb). 2015 May 20:97:e11. doi: 10.1017/S0016672315000105.

Abstract

Background: A 40 kb ancestral germline duplication upstream of the GREM1 gene was reported in Ashkenazi families with hereditary mixed polyposis syndrome (HMPS).

Objective: Assess the contribution of the GREM1 mutation to familial colorectal cancer (CRC) in Ashkenazim.

Methods: Jewish Ashkenazi individuals (n = 472 155 males, 317 females) were genotyped for the GREM1 duplication, 194 with CRC, 131 had other cancer types (endometrial, pancreatic and ovarian) that show a syndromic association with CRC, and 147 were cancer-free with a suggestive family history of CRC.

Results: One mutation carrier was found who fulfills the Amsterdam criteria for Lynch Syndrome (LS). The prevalence of this mutation amongst LS Ashkenazim is 0·7%.

Conclusion: If validated in additional studies it seems rational to recommend to look for the GREM1 founder mutation in Ashkenazi individuals with multiple colorectal polyps and/or fulfill the criteria for LS.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Colorectal Neoplasms / diagnosis
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms, Hereditary Nonpolyposis / diagnosis
  • Colorectal Neoplasms, Hereditary Nonpolyposis / genetics
  • DNA Mutational Analysis
  • Family Health
  • Female
  • Genetic Predisposition to Disease / genetics*
  • Genetic Testing
  • Germ-Line Mutation*
  • Humans
  • Intercellular Signaling Peptides and Proteins / genetics*
  • Jews / genetics
  • Male
  • Middle Aged
  • Young Adult

Substances

  • GREM1 protein, human
  • Intercellular Signaling Peptides and Proteins