eprintid: 10073989 rev_number: 24 eprint_status: archive userid: 608 dir: disk0/10/07/39/89 datestamp: 2019-05-16 13:12:41 lastmod: 2021-10-15 22:59:18 status_changed: 2019-05-16 13:12:41 type: article metadata_visibility: show creators_name: Wadsworth, CA creators_name: Dixon, PH creators_name: Taylor-Robinson, S creators_name: Kim, JU creators_name: Zabron, AA creators_name: Wong, JH creators_name: Chapman, MH creators_name: McKay, SC creators_name: Spalding, DR creators_name: Wasan, HS creators_name: Pereira, SP creators_name: Thomas, HC creators_name: Whittaker, JC creators_name: Williamson, C creators_name: Khan, SA title: Polymorphisms in Natural Killer Cell Receptor Protein 2D (NKG2D) as a Risk Factor for Cholangiocarcinoma ispublished: pub divisions: UCL divisions: B02 divisions: C10 divisions: D17 divisions: G91 keywords: CC, cholangiocarcinoma, GWAS, genome wide association study, NK, natural killer, NKG2D, NKG2D, natural killer cell receptor protein G2D, PSC, primary sclerosing cholangitis, SNP, single nucleotide polymorphism, cholangiocarcinoma, genetic, risk factor note: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. abstract: Background and aims: Understanding of the significant genetic risk factors for Cholangiocarcinoma (CC) remains limited. Polymorphisms in the natural killer cell receptor G2D (NKG2D) gene have been shown to increase risk of CC transformation in patients with Primary Sclerosing Cholangitis (PSC). We present a validation study of NKG2D polymorphisms in CC patients without PSC. Methods: Seven common Single Nucleotide Polymorphisms (SNPs) of the NKG2D gene were genotyped in 164 non-PSC related CC subjects and 257 controls with HaploView. The two SNPs that were positively identified in the previous Scandinavian study, rs11053781 and rs2617167, were included. Results: The seven genotyped SNPs were not associated with risk of CC. Furthermore, haplotype analysis revealed that there was no evidence to suggest that any haplotype differs in frequency between cases and controls (P > 0.1). Conclusion: The common genetic variation in NKG2D does not correlate significantly with sporadic CC risk. This is in contrast to the previous positive findings in the Scandinavian study with PSC-patients. The failure to reproduce the association may reflect an important difference between the pathogenesis of sporadic CC and that of PSC-related CC. Given that genetic susceptibility is likely to be multifaceted and complex, further validation studies that include both sporadic and PSC-related CC are required. date: 2019-03 date_type: published official_url: https://doi.org/10.1016/j.jceh.2018.06.521 oa_status: green full_text_type: other pmcid: PMC6477142 language: eng primo: open primo_central: open_green verified: verified_manual elements_id: 1653617 doi: 10.1016/j.jceh.2018.06.521 pii: S0973-6883(18)30609-1 lyricists_name: Pereira, Stephen lyricists_id: SPPER57 actors_name: Allington-Smith, Dominic actors_id: DAALL44 actors_role: owner full_text_status: public publication: Journal of Clinical and Experimental Hepatology volume: 9 number: 2 pagerange: 171-175 event_location: India issn: 0973-6883 citation: Wadsworth, CA; Dixon, PH; Taylor-Robinson, S; Kim, JU; Zabron, AA; Wong, JH; Chapman, MH; ... Khan, SA; + view all <#> Wadsworth, CA; Dixon, PH; Taylor-Robinson, S; Kim, JU; Zabron, AA; Wong, JH; Chapman, MH; McKay, SC; Spalding, DR; Wasan, HS; Pereira, SP; Thomas, HC; Whittaker, JC; Williamson, C; Khan, SA; - view fewer <#> (2019) Polymorphisms in Natural Killer Cell Receptor Protein 2D (NKG2D) as a Risk Factor for Cholangiocarcinoma. Journal of Clinical and Experimental Hepatology , 9 (2) pp. 171-175. 10.1016/j.jceh.2018.06.521 <https://doi.org/10.1016/j.jceh.2018.06.521>. Green open access document_url: https://discovery.ucl.ac.uk/id/eprint/10073989/1/Pereira_Wadsworth%20et%20al%20NKG2D_CW_STR_JCEH.pdf