<i>HLA</i>and<i>KIR</i>Associations of Cervical Neoplasia

Bao, Xiaojing; Hanson, Aimee L.; Madeleine, Margaret M.; Wang, Sophia; Schwartz, Stephen M.; Newell, Felicity; Pettersson-Kymmer, Ulrika; Hemminki, Kari; Tiews, Sven; Steinberg, Winfried; Rader, Janet S.; Castro, Felipe A.; Safaeian, Mahboobeh; Franco, Eduardo L.; Coutlée, François; Ohlsson, Claes; Cortés, Adrián; Marshall, Mhairi; Mukhopadhyay, Pamela; Cremin, Katie; Johnson, Lisa G.; Garland, Suzanne M.; Tabrizi, Sepehr N.; Wentzensen, Nicolas; Sitas, Freddy; Trimble, Cornelia L.; Little, Julian; Cruickshank, Margaret; Frazer, Ian H.; Hildesheim, Allan; Brown, Matthew A.; Duncan, Emma L.; Sun, Ying; Leo, Paul

doi:10.1093/infdis/jiy483

Cited by 25 publications

(23 citation statements)

References 29 publications

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“…These findings are consistent with previous reports of KIR and HLA genotyping, indicating that the absence of HLA ligands for inhibitory KIRs could be associated with a significant reduction of CMV infection [11]. The cumulative evidence shows that KIR2DL2 –HLA-C1 and KIR2DL3 may be molecular biomarkers of virus-induced diseases [22,23,24].…”

Section: Discussionsupporting

confidence: 91%

Killer Immunoglobulin-Like Receptor 2DS2 (KIR2DS2), KIR2DL2-HLA-C1, and KIR2DL3 as Genetic Markers for Stratifying the Risk of Cytomegalovirus Infection in Kidney Transplant Recipients

Dęborska−Materkowska

Perkowska‐Ptasińska

Sadowska-Jakubowicz

et al. 2019

IJMS

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Infection with cytomegalovirus (CMV) remains a major problem in kidney transplant recipients, resulting in serious infectious complications and occasionally mortality. Accumulating evidence indicates that natural killer cell immunoglobulin-like receptors (KIRs) and their ligands affect the susceptibility to various diseases, including viral infections (e.g., CMV infection). We investigated whether KIR genes and their ligands affect the occurrence of CMV infection in a group of 138 kidney transplant recipients who were observed for 720 days posttransplantation. We typed the recipients for the presence of KIR genes (human leukocyte antigen C1 [HLA-C1], HLA-C2, HLA-A, HLA-B, and HLA-DR1) by polymerase chain reaction with sequence-specific primers. The multivariate analysis revealed that the lack of KIR2DS2 (p = 0.035), the presence of KIR2DL3 (p = 0.075), and the presence of KIR2DL2–HLA-C1 (p = 0.044) were risk factors for posttransplant CMV infection. We also found that a lower estimated glomerular filtration rate (p = 0.036), an earlier time of antiviral prophylaxis initiation (p = 0.025), lymphocytopenia (p = 0.012), and pretransplant serostatus (donor-positive/recipient-negative; p = 0.042) were independent risk factors for posttransplant CMV infection. In conclusion, our findings confirm that the KIR/HLA genotype plays a significant role in anti-CMV immunity and suggest the contribution of both environmental and genetic factors to the incidence of CMV infection after kidney transplantation.

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Section: Discussionsupporting

confidence: 91%

Killer Immunoglobulin-Like Receptor 2DS2 (KIR2DS2), KIR2DL2-HLA-C1, and KIR2DL3 as Genetic Markers for Stratifying the Risk of Cytomegalovirus Infection in Kidney Transplant Recipients

Dęborska−Materkowska

Perkowska‐Ptasińska

Sadowska-Jakubowicz

et al. 2019

IJMS

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“…9,11 The human leukocyte antigen (HLA) locus controls several hostpathogen interactions and has been proposed as a cervical cancer susceptibility locus in different populations. [12][13][14][15][16] A cervical cancer genome-wide association study (GWAS) in the Swedish population implicated rs9272143, located at the HLA-DQA1 gene and rs2516448, located downstream of the MHC class I polypeptiderelated sequence A (MICA), with increased susceptibility to cervical cancer. 12,13 It has remained largely unknown which genes or functional consequences underlie this association.…”

Section: Introductionmentioning

confidence: 99%

Association of genomic variants at the human leukocyte antigen locus with cervical cancer risk, HPV status and gene expression levels

Ramachandran

Schürmann

Mao

et al. 2020

Intl Journal of Cancer

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The human leukocyte antigen (HLA) locus on chromosome 6 has been reported to be associated with cervical cancer. We investigated two independent single‐nucleotide polymorphisms in a large case‐control series of cervical dysplasia and carcinoma that has been newly established by the German Cervigen Consortium, comprising a total of 2481 cases and 1556 healthy females. We find significant associations for both variants, rs9272117 at HLA‐DQA1 and rs2844511 at MICA and HCP5, with cervical disease. Both variants showed evidence of association with invasive cervical cancer (rs9272117: OR 0.89, 95% CI 0.79‐0.99, P = .036; rs2844511: OR 1.17, 95% CI 1.04‐1.31, P = .008) and with high‐grade dysplasia (rs9272117: OR 0.78, 95% CI 0.70‐0.87, P = 7.1 × 10−6; rs2844511: OR 1.13, 95% CI 1.01‐1.26, P = .035), as well as in a combined analysis of both groups (rs9272117: OR 0.83, 95% CI 0.75‐0.91, P = 6.9 × 10−5; rs2844511: OR 1.14, 95% CI 1.04‐1.26, P = .005). Variant rs2844511, but not rs9272117, also showed modest evidence of association with low‐grade dysplasia (OR 1.26, 95% CI 1.04‐1.54, P = .019). In case‐only analyses, rs2844511 tended to predict HPV status (P = .044) and rs9272117 tended to associate with HPV16 (P = .022). RNA studies in cervical samples showed a significant correlation in the transcript levels of MICA, HCP5 and HLA‐DQA1, suggesting extensive co‐regulation. All three genes were upregulated in HPV16‐positive samples. In stratified analyses, rs9272117 was associated with HLA‐DQA1 levels, specifically in HPV‐positive samples, while rs2844511 was associated with MICA and HCP5 levels. The risk allele of rs2844511 was required for correlations between MICA or HCP5 with HLA‐DQA1. Altogether, our results support 6p21.32‐33 as the first consistent cervical cancer susceptibility locus and provide evidence for a link between genetic risk variants, HPV16 status and transcript levels of HLA‐DQA1, HCP5 and MICA, which may contribute to tumor immune evasion.

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“…How can we consolidate the findings? Inherited genetic factors are likely to contribute to the associations, and for example in cervical cancer certain human leukocyte antigen (HLA) alleles show strong risk 14,15 . However, we need to consider also the contribution by other non-genetic risk factors, such as HPV-infection and smoking.…”

Section: Discussionmentioning

confidence: 99%

Familial Clustering, Second Primary Cancers and Causes of Death in Penile, Vulvar and Vaginal Cancers

Zhang

Hemminki

Chen

et al. 2019

Sci Rep

Self Cite

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Data on familial risks in penile and vulvar/vaginal cancers and in second primary cancers (SPCs) following these cancers are limited. We used the Swedish Family-Cancer Database from years 1958 through 2015 to identify 3641 penile and 8856 vulvar/vaginal cancers and to calculate relative risks (RRs) and 95% confidence intervals (CIs) for these cancers according to site-specific cancer in family members; additionally risk for SPCs was calculated. The familial RR for concordant (same) penile cancer was 3.22 (1.34–7.74), and it was 2.72 (1.69–4.39) for vulvar/vaginal cancer; RRs were increased for vulvar/vaginal cancer in families of anal cancer patients. RR for second penile cancer after penile cancers was 11.68 (7.95–17.18), while that for concordant vulvar/vaginal cancer was 9.03 (7.31–11.15). SPCs were diagnosed in 16.8% of penile cancer patients and in them 45.9% of deaths were caused by SPC (other than penile cancer). In vulvar/vaginal cancer patients with SPC, 36.4% of deaths were due to SPC. The results showed that these genital cancers might run in families and as SPCs are associated with human papilloma virus and smoking related cancers. Risk for these genital and anal SPCs are high and a follow-up plan should be agreed at diagnosis of these cancers.

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HLAandKIRAssociations of Cervical Neoplasia

Abstract: Our findings suggest that HLA-C1 group alleles play a role in protecting against HPV16-related cervical neoplasia, mainly through a KIR-mediated mechanism.

Cited by 25 publications

References 29 publications

Killer Immunoglobulin-Like Receptor 2DS2 (KIR2DS2), KIR2DL2-HLA-C1, and KIR2DL3 as Genetic Markers for Stratifying the Risk of Cytomegalovirus Infection in Kidney Transplant Recipients

Killer Immunoglobulin-Like Receptor 2DS2 (KIR2DS2), KIR2DL2-HLA-C1, and KIR2DL3 as Genetic Markers for Stratifying the Risk of Cytomegalovirus Infection in Kidney Transplant Recipients

Association of genomic variants at the human leukocyte antigen locus with cervical cancer risk, HPV status and gene expression levels

Familial Clustering, Second Primary Cancers and Causes of Death in Penile, Vulvar and Vaginal Cancers

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