PMID- 24420788
OWN - NLM
STAT- MEDLINE
DCOM- 20150207
LR  - 20221207
IS  - 1573-7292 (Electronic)
IS  - 1389-9600 (Linking)
VI  - 13
IP  - 2
DP  - 2014 Jun
TI  - The MUTYH hotspot mutations p.G396D and p.Y179C do not cause substantial genetic 
      susceptibility to biliary cancer.
PG  - 243-7
LID - 10.1007/s10689-014-9699-2 [doi]
AB  - Inflammation-associated oxidative stress and DNA damage are involved in malignant 
      transformation of cholangiocytes. Defective DNA repair mechanisms may predispose 
      to cholangiocarcinoma (CCA) formation, and an elevated CCA risk for MutY human 
      homologue (MUTYH) germline mutation carriers has been proposed previously. The 
      aim of this study was to re-evaluate the MUTYH hotspot mutations p.Y179C 
      (rs34612342) and p.G396D (rs36053993) as genetic susceptibility factors in a 
      large CCA cohort. The study population consisted of 219 Caucasian CCA patients 
      (66.2 +/- 11.9 years, 130 males, 89 females; 43 intrahepatic and 176 extrahepatic 
      tumours; tissue diagnosis in 77.6 %) and 355 healthy controls (61.0 +/- 11.0 years; 
      158 males, 197 females). MUTYH hotspot variants were genotyped using TaqMan 
      assays. Four CCA patients were monoallelic mutation carriers (3 p.G396D; 1 
      p.Y179C) whereas 6 control subjects were heterozygotes (5 p.G396D; 1 p.Y179C). 
      None of the patients carried a biallelic hotspot mutation. The observed allele 
      frequencies did not differ significantly between cases and controls (p > 0.05) 
      and association tests did not provide evidence for an involvement of p.Y179C (OR 
      1.6 [95 % CI 0.1-26.0]) or p.G396D (OR 1.0 [95 % CI 0.2-4.1]) in the 
      susceptibility to CCA. Power analysis identified a sufficient power only for 
      large effect sizes (>90 % for OR > 5.8 for p.G396D and OR > 18.5 for p.Y179C). 
      Monoallelic MUTYH hotspot mutations do not act as major genetic susceptibility 
      factors causing a substantial CCA risk in the Caucasian population. Due to the 
      low statistical power for the identification of small effect sizes, much larger 
      studies will be needed to detect such effects of minor clinical significance.
FAU - Casper, M
AU  - Casper M
AD  - Department of Medicine II, Saarland University Medical Center, Kirrberger Strasse 
      100, 66421, Homburg, Germany, markus.casper@uks.eu.
FAU - Acalovschi, M
AU  - Acalovschi M
FAU - Lammert, F
AU  - Lammert F
FAU - Zimmer, V
AU  - Zimmer V
LA  - eng
PT  - Journal Article
PL  - Netherlands
TA  - Fam Cancer
JT  - Familial cancer
JID - 100898211
RN  - EC 3.2.2.- (DNA Glycosylases)
RN  - EC 3.2.2.- (mutY adenine glycosylase)
SB  - IM
MH  - Aged
MH  - Bile Duct Neoplasms/*genetics
MH  - *Bile Ducts, Intrahepatic
MH  - Case-Control Studies
MH  - Cholangiocarcinoma/*genetics
MH  - DNA Glycosylases/*genetics
MH  - Female
MH  - Gene Frequency
MH  - Genetic Predisposition to Disease/*genetics
MH  - Heterozygote
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Mutation
MH  - White People/genetics
EDAT- 2014/01/15 06:00
MHDA- 2015/02/11 06:00
CRDT- 2014/01/15 06:00
PHST- 2014/01/15 06:00 [entrez]
PHST- 2014/01/15 06:00 [pubmed]
PHST- 2015/02/11 06:00 [medline]
AID - 10.1007/s10689-014-9699-2 [doi]
PST - ppublish
SO  - Fam Cancer. 2014 Jun;13(2):243-7. doi: 10.1007/s10689-014-9699-2.