|| increased colon cancer risk
|| common in clinvar
rs1801166, also known as c.3949G>C, p.Glu1317Gln and E1317Q, represents a rare variant in the APC gene on chromosome 5.
There are conflicting views on whether the minor rs1801166(C) allele increases risk for familial adenomatous polyposis (FAP), a disorder often leading to colorectal cancer. One publication states the presence of this minor allele raises the risk of colon cancer 11 fold; other publications find no increase in risk.
Note that normally, APC gene mutations associated with FAP are dominant (and highly penetrant). Given that, the most conservative conclusion would be to say that if it's pathogenic at all, the E1317Q mutation is likely to lead to significantly increased risk primarily in rs1801166(C;C) homozygotes, but it might also be worth suggesting increased screening for heterozygotes anyway, and most especially for any E1317Q carriers with a family history of colon cancer.
[PMID 9724771] The APC variants I1307K and E1317Q are associated with colorectal tumors, but not always with a family history.
[PMID 11001924] Germline APC variants in patients with multiple colorectal adenomas, with evidence for the particular importance of E1317Q.
|| Moderate clinical importance, Uncertain pathogenic
|| This rare variant has been hypothesized to increase risk of colon cancer. Later studies have contradicted this, finding no significant enrichment and concluding the variant does not increase risk.
[PMID 17119068] APC E1317Q is not associated with Colorectal Cancer in a population-based case-control study in Northern Israel.
[PMID 23846443] Detailed molecular genetics of the APC*E1317Q mutation in tumor tissue suggest it may not be pathologically significant
[PMID 26863316] Detection of a Tumor Suppressor Gene Variant Predisposing to Colorectal Cancer in an 18th Century Hungarian Mummy.