@article{4da73503671e4d1eb012821a725d535e,
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).",
author = "Ward, {Christopher J.} and Yanhong Wu and Johnson, {Ruth A.} and Woollard, {John R.} and Bergstralh, {Eric J.} and Cicek, {Mine S.} and Jason Bakeberg and Sandro Rossetti and Heyer, {Christina M.} and Petersen, {Gloria M.} and Lindor, {Noralene M.} and Thibodeau, {Stephen N.} and Harris, {Peter C.} and Torres, {Vicente E.} and Hogan, {Marie C.} and Boardman, {Lisa A.}",
note = "Funding Information: Acknowledgments Funding for the TaqMan assay was provided by the Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN, Research Committee and the PKD Foundation. This work was supported by the Clinical Core of the Mayo Clinic Center for Cell Signaling in Gastroenterology (P30DK084567); Mayo Clinic SPORE in Pancreatic Cancer (P50 CA102701); the Lustgarten Foundation for Pancreatic Cancer Research and National Institutes of Health R01 grants DK59597 and DK065056. This work was supported by the National Cancer Institute, National Institutes of Health under RFA # CA-95-011 and through cooperative agreements with members of the Colon Cancer Family Registry and P.I.s. Collaborating centers include {\textquoteleft}{\textquoteleft}Australasian Colorectal Cancer Family Registry (U01 CA097735){\textquoteright}{\textquoteright}, {\textquoteleft}{\textquoteleft}Familial Colorectal Neoplasia Collaborative Group (U01 CA074799){\textquoteright}{\textquoteright}, [USC] {\textquoteleft}{\textquoteleft}Mayo Clinic Cooperative Family Registry for Colon Cancer Studies (U01 CA074800){\textquoteright}{\textquoteright}, {\textquoteleft}{\textquoteleft}Ontario Registry for Studies of Familial Colorectal Cancer (U01 CA074783){\textquoteright}{\textquoteright}, {\textquoteleft}{\textquoteleft}Seattle Colorectal Cancer Family Registry (U01 CA074794){\textquoteright}{\textquoteright}, {\textquoteleft}{\textquoteleft}University of Hawaii Colorectal Cancer Family Registry (U01 CA074806){\textquoteright}{\textquoteright}, {\textquoteleft}{\textquoteleft}University of California, Irvine Informatics Center (U01 CA078296){\textquoteright}{\textquoteright}.",
year = "2011",
month = mar,
doi = "10.1007/s00439-011-0950-8",
language = "English (US)",
volume = "129",
pages = "345--349",
journal = "Human genetics",
issn = "0340-6717",
publisher = "Springer Verlag",
number = "3",
}