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

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.