Genetic risk factor for cholangiocarcinoma in PSC

[Guest guest]

Thanks for posting this article. It's nice to know that they are making progress in this arena!

Check out AOL Money Finance's list of the hottest products and top money wasters of 2007.

[Guest guest]

Dear Dave,

Thanks for posting this study on risk of CC. Also a great newsletter as usual. Thanks for all the hard work. I was obviously late with article for you but I had to go to Pitt which derailed my plans. But I will get it to you for the Dec. issue.

Happy Thanksgiving to you and your family.

Ali

Save Life - Be A Live Donor and An Organ and Tissue DonorAli Lingerfelt-Tait180 Blackberry Inn Rd.Weaverville, N.C. 28787www.caringbridge.compassword - alilingerfelttaitalso check out :http.//health.groups.yahoo.com/group/Livertx-PSC/It's a new sister site from the PSC Support Group that is for transplant issues.www.pscpartners.orgPSC Partners Support GroupBuy Notecards and Support Research for PSCCheck out AOL Money Finance's list of the hottest products and top money wasters of 2007.

[Guest guest]

Hepatology. 2007 Nov 19; [Epub ahead of print]

Cholangiocarcinoma in primary sclerosing cholangitis is associated

with NKG2D polymorphisms.

Melum E, Karlsen TH, Schrumpf E, Bergquist A, Thorsby E, Boberg KM,

Lie BA

Medical Department, Rikshospitalet]Radiumhospitalet Medical Center,

Oslo, Norway.

Primary sclerosing cholangitis (PSC) is often complicated by the

development of cholangiocarcinoma (CCA). Genetic variation of natural

killer cell receptor G2D (NKG2D) has been associated with cancer

susceptibility. An important ligand for NKG2D, major

histocompatibility complex class I chain-related molecule A (MICA),

serves as a marker of cellular stress. The 5.1 allele of the gene

encoding MICA has been associated with PSC. In this study, we aimed

to investigate the influence of genetic variations in the NKG2D-MICA

receptor-ligand pair on the risk of CCA in patients with PSC. Seven

single nucleotide polymorphisms (SNPs) covering the NKG2D gene were

genotyped in 365 Scandinavian PSC patients and 368 healthy controls

with TaqMan technology. Genotype data on the MICA 5.1 variant were

available from previous studies. Forty-nine of the PSC patients

(13.6%) had developed CCA at the time of study. Two of the NKG2D SNPs

were associated with an increased risk of CCA: rs11053781 [odds ratio

(OR) = 2.08, 95% confidence interval (CI) = 1.31-3.29, corrected P (P

©) = 0.011] and rs2617167 (OR = 2.32, 95% CI = 1.47-3.66, P© =

0.0020). rship of the MICA 5.1 allele was associated with

resistance against CCA (OR = 0.43, 95% CI = 0.20-0.95, not corrected

P = 0.032). Conclusion: Our results show that genetic variants of the

NKG2D receptor are associated with development of CCA in PSC

patients. This suggests that interaction between NKG2D and MICA is

involved in protection against CCA in PSC. Patients who are

homozygous for the nonrisk alleles are unlikely to develop CCA; this

finding could be helpful in identifying PSC patients with a low CCA

risk. PMID: 18023027.