Identification of the <i>NKG2D</i> Haplotypes Associated with Natural Cytotoxic Activity of Peripheral Blood Lymphocytes and Cancer Immunosurveillance

Hayashi, Tomonori; Imai, Kazue; Morishita, Yukari; Hayashi, Ikue; Kusunoki, Yoichiro; Nakachi, Kei

doi:10.1158/0008-5472.can-05-2776

Cited by 114 publications

(158 citation statements)

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“…The haplotype frequencies of LNK1/LNK1, HNK1/LNK1 and HNK1/HNK1 were 43%, 42% and 15%, respectively in donors and 35%, 45% and 20%, respectively in recipients. These frequencies were similar to those reported in previous studies in Japanese populations 21,24 and were in accordance with the Hardy-Weinberg equilibrium (p=0.80).…”

Section: Frequencies Of Nkg2d Haplotypesupporting

confidence: 91%

“…C_9345347_10; Applied Biosystems) for rs1049174, a single locus featuring a G-C substitution to distinguish between the HNK1 (G) and LNK1 (C) haplotypes of the NKG2D gene. 21,23,24 Data management and statistical analysis Data were collected by the JMDP using a standardized report form. Follow-up reports were submitted at 100 days, 1 year and annually after transplantation.…”

Section: Nkg2d Genotypingmentioning

confidence: 99%

“…[16][17][18]20 Recently, SNP were identified between LNK1 and HNK1 haplotypes of the NKG2D gene. 21 In Japanese individuals, the HNK1 haplotype is associated with greater activity of NK cells in the peripheral blood 21,22 and a lower prevalence of cancers originating from epithelial cells. 21,23,24 The present study investigates the impact of donor and recipient polymorphisms in the NKG2D gene on the clinical outcomes of patients undergoing allogeneic myeloablative bone marrow transplantation using an HLA allele-matched unrelated donor.…”

Section: Introductionmentioning

confidence: 99%

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NKG2D gene polymorphism has a significant impact on transplant outcomes after HLA-fully-matched unrelated bone marrow transplantation for standard risk hematologic malignancies

et al. 2009

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BackgroundNKG2D, an activating and co-stimulatory receptor expressed on natural killer cells and T cells, plays pivotal roles in immunity to microbial infections as well as in cancer immunosurveillance. This study examined the impact of donor and recipient polymorphisms in the NKG2D gene on the clinical outcomes of patients undergoing allogeneic T-cell-replete myeloablative bone marrow transplantation using an HLA-matched unrelated donor. Design and MethodsThe NKG2D polymorphism was retrospectively analyzed in a total 145 recipients with hematologic malignancies and their unrelated donors. The patients underwent transplantation following myeloablative conditioning; the recipients and donors were matched through the Japan Marrow Donor Program. ResultsIn patients with standard-risk disease, the donor NKG2D-HNK1 haplotype, a haplotype expected to induce greater natural killer cell activity, was associated with significantly improved overall survival (adjusted hazard ratio, 0.44; 95% confidence interval, 0.23 to 0.85; p=0.01) as well as transplant related mortality (adjusted hazard ratio, 0.42; 95% confidence interval, 0.21 to 0.86; p=0.02), but had no impact on disease relapse or the development of grade II-IV acute graft-versus-host disease or chronic graft-versus-host disease. The NKG2D polymorphism did not significantly influence the transplant outcomes in patients with high-risk disease. ConclusionsThese data suggest an association between the donor HNK1 haplotype and better clinical outcome among recipients, with standard-risk disease, of bone marrow transplants from HLA-matched unrelated donors.

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Section: Frequencies Of Nkg2d Haplotypesupporting

confidence: 91%

Section: Nkg2d Genotypingmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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NKG2D gene polymorphism has a significant impact on transplant outcomes after HLA-fully-matched unrelated bone marrow transplantation for standard risk hematologic malignancies

et al. 2009

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“…MICA functions as a ligand for the activating NKG2D receptor on NK cells [66] . It was recently recognised that the two risk haplotypes in question share alleles not only at MICA, but also at the neighbouring HLA-B and -C loci, when these are defined according to the KIR binding properties of the HLA classⅠ molecules [67] .…”

Section: The Hla Complex and Genetic Associations Observed In Pscmentioning

confidence: 99%

“…Recently, a highly significant association between polymorphisms in the NKG2D gene and cholangiocarcinoma in PSC was detected [71] . Previous studies have highlighted the importance of this activating NK cell receptor in protection against other cancer types [66] . Persistent exposure to effector molecules of inflammatory pathways (e.g., IL-6 [101] ), along with chronic cholestasis [102] , is probably important for the malignant transformation of cholangiocytes.…”

Section: Genetic Associations With Clinical Subsets Of Psc Patientsmentioning

confidence: 99%

Genetic epidemiology of primary sclerosing cholangitis

Karlsen

Schrumpf²,

Boberg³

2007

WJG

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The aetiology of primary sclerosing cholangitis (PSC) is not known. A more than 80-fold increased risk of PSC among first-degree relatives emphasizes the importance of genetic factors. Genetic associations within the human leukocyte antigen (HLA) complex on chromosome 6p21 were detected in PSC 25 years ago. Subsequent studies have substantiated beyond doubt that one or more genetic variants located within this genetic region are important. The true identities of these variants, however, remain to be identified. Several candidate genes at other chromosomal loci have also been investigated. However, according to strict criteria for what may be denominated a susceptibility gene in complex diseases, no such gene exists for PSC today. This review summarises present knowledge on the genetic susceptibility to PSC, as well as genetic associations with disease progression and clinical subsets of particular interest (inflammatory bowel disease and cholangiocarcinoma).

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Incorporation of Inter‐individual Heterogeneity into the Multistage Carcinogenesis Model: Approach to the Analysis of Cancer Incidence Data

Izumi

Ohtaki

2007

Biometrical J

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We investigate a multistage carcinogenesis frailty model to incorporate inter-individual heterogeneity into carcinogenic response. Attention is focused on inference concerning the effects of different sources of population heterogeneity on cancer rates. The authors consider unobserved variability arising from either carcinogen exposure or background characteristics. Gamma and Inverse-Gaussian distributions are selected for frailty models, and the baseline hazard function is the generalized Armitage-Doll model (i.e. non-frailty model) in which exposure effects shift the age scale instead of acting multiplicatively on cancer rates. For illustration, we apply the method to solid cancer data from a cohort of atomic bomb survivors to examine some features of proposed models. The results show that the Gamma frailty model for the heterogeneity of baseline rates provides the best goodness-of-fit of the model and a non-zero frailty variance. Parameter estimates are, for the most part, comparable between the Gamma and Inverse-Gaussian frailty models. In a heterogeneous population the exposure effects on young adulthood cancer rates might be underestimated for the non-frailty model. Meaningful information regarding each source of heterogeneity has been provided by the proposed method. Therefore, the multistage carcinogenesis frailty model approach is useful for analyses of epidemiological cancer data to assess population heterogeneity and heterogeneity-influenced exposure effects.

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Identification of the NKG2D Haplotypes Associated with Natural Cytotoxic Activity of Peripheral Blood Lymphocytes and Cancer Immunosurveillance

Cited by 114 publications

References 30 publications

NKG2D gene polymorphism has a significant impact on transplant outcomes after HLA-fully-matched unrelated bone marrow transplantation for standard risk hematologic malignancies

NKG2D gene polymorphism has a significant impact on transplant outcomes after HLA-fully-matched unrelated bone marrow transplantation for standard risk hematologic malignancies

Genetic epidemiology of primary sclerosing cholangitis

Incorporation of Inter‐individual Heterogeneity into the Multistage Carcinogenesis Model: Approach to the Analysis of Cancer Incidence Data

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