title: Germline PKHD1 mutations are protective against colorectal cancer.
abstract: The autosomal recessive polycystic kidney disease (ARPKD) gene, PKHD1, has been implicated in the genesis or growth of colorectal adenocarcinoma, as a high level of somatic mutations was found in colorectal tumor tissue. To determine whether carriers of a single PKHD1 mutation are at increased risk of colorectal carcinoma, we assessed the prevalence of the commonest European mutation, T36M. First, we assayed a European cohort of ARPKD patients and found T36M was responsible for 13.1% of mutations. We then investigated two European cohorts with colorectal adenocarcinoma versus two control cohorts of similar age and gender. Screening for the most common PKHD1 mutation, T36M, we detected 15:3,603 (0.42%) controls versus 1:3,767 (0.027%) colorectal cancer individuals, indicating that heterozygous PKHD1 mutations are not a risk factor and are protective (p=0.0002). We also show that the carriage rate for PKHD1 mutations in the European population is higher than previous accepted at 3.2% (1:31 genomes).
authors.affiliation: Division of Nephrology and Hypertension, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA. ward.christopher@mayo.edu
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Ward
authors.forename: Yanhong
authors.initials: Y
authors.lastname: Wu
authors.forename: Ruth A
authors.initials: RA
authors.lastname: Johnson
authors.forename: John R
authors.initials: JR
authors.lastname: Woollard
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Bergstralh
authors.forename: Mine S
authors.initials: MS
authors.lastname: Cicek
authors.forename: Jason
authors.initials: J
authors.lastname: Bakeberg
authors.forename: Sandro
authors.initials: S
authors.lastname: Rossetti
authors.forename: Christina M
authors.initials: CM
authors.lastname: Heyer
authors.forename: Gloria M
authors.initials: GM
authors.lastname: Petersen
authors.forename: Noralene M
authors.initials: NM
authors.lastname: Lindor
authors.forename: Stephen N
authors.initials: SN
authors.lastname: Thibodeau
authors.forename: Peter C
authors.initials: PC
authors.lastname: Harris
authors.forename: Vicente E
authors.initials: VE
authors.lastname: Torres
authors.forename: Marie C
authors.initials: MC
authors.lastname: Hogan
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Boardman
mesh_terms: D000230:Adenocarcinoma / Q000453:epidemiology / Q000235:genetics*; D000368:Aged; D015331:Cohort Studies; D015179:Colorectal Neoplasms / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D018095:Germ-Line Mutation; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D015995:Prevalence; D011956:Receptors, Cell Surface / Q000235:genetics*; D044465:White People / Q000235:genetics
chemical_list: C451750:PKHD1 protein, human; D011956:Receptors, Cell Surface