title: Inherited deleterious variants in GALNT12 are associated with CRC susceptibility.
abstract: A recent report detailed the occurrence of both somatic and constitutional variants in the GALNT12 gene, located at 9q22.33, in some colorectal cancer (CRC) patients. In this study, we investigate the occurrence of inherited deleterious variants in GALNT12 in 118 families referred to a cancer genetics clinic. We discovered two deleterious variants (c.907G>A (p.Asp303Asn); c.1187A>G (p.Tyr396Cys)) in 4/118 probands. The variants, which were not found in 149 control individuals (P = 0.0376), cosegregate with CRC and/or adenomatous polyps in other family members. The probability by chance that cosegregation of c.907G>A with CRC and/or adenomatous polyps occurred, in the two pedigrees combined, was 1.56%. Although this study does not provide irrefutable evidence that GALNT12 variants are highly penetrant alleles that predispose to CRC in the majority of unexplained hereditary CRC families, it does provide additional evidence to support an important role of these variants in a proportion of this considerable high-risk group.
authors.affiliation: Discipline of Genetics, Memorial University, St. John's, Newfoundland, Canada.
authors.forename: Erica
authors.initials: E
authors.lastname: Clarke
authors.forename: Roger C
authors.initials: RC
authors.lastname: Green
authors.forename: Jane S
authors.initials: JS
authors.lastname: Green
authors.forename: Krista
authors.initials: K
authors.lastname: Mahoney
authors.forename: Patrick S
authors.initials: PS
authors.lastname: Parfrey
authors.forename: H Banfield
authors.initials: HB
authors.lastname: Younghusband
authors.forename: Michael O
authors.initials: MO
authors.lastname: Woods
mesh_terms: D015179:Colorectal Neoplasms / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D009154:Mutation; D017350:N-Acetylgalactosaminyltransferases / Q000235:genetics*
chemical_list: C465011:GALNT12 protein, human; D017350:N-Acetylgalactosaminyltransferases