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MHC loci affecting cervical cancer risk: distinguishing the effects of HLA-DQB1 and non-HLA genes TNF, LTA, TAP1 and TAP2

Genes & Immunity volume 9, pages 613–623 (2008)Cite this article

Abstract

Cervical cancer has been associated with specific human leukocyte antigen (HLA) haplotypes/alleles and with polymorphisms at the nearby non-HLA loci TNF, LTA, TAP1 and TAP2. Distinguishing effects of individual loci in the major histocompatibility complex (MHC) region are difficult due to the complex linkage disequilibrium (LD) pattern characterized by high LD, punctuated by recombination hot spots. We have evaluated the association of polymorphism at HLA class II DQB1 and the TNF, LTA, TAP1 and TAP2 genes with cervical cancer risk, using 1306 familial cases and 288 controls. DQB1 was strongly associated; alleles *0301, *0402 and *0602 increased cancer susceptibility, whereas *0501 and *0603 decreased susceptibility. Among the non-HLA loci, association was only detected for the TAP2 665 polymorphism, and interallelic disequilibrium analysis indicated that this could be due to LD with DQB1. As the TAP2 665 association was seen predominantly in non-carriers of DQB1 susceptibility alleles, we hypothesized that TAP2 665 may have an effect not attributable to LD with DQB1. However, a logistic regression analysis suggested that TAP2 665 was strongly influenced by LD with DQB1. Our results emphasize the importance of large sample sizes and underscore the necessity of examining both HLA and non-HLA loci in the MHC to assign association to the correct locus.

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Acknowledgements

We are grateful to all women who participated in this study. This work was funded by grants to UBG from the Swedish Cancer Society and the Knut and Alice Wallenberg Foundation, Sweden. PKEM acknowledges support from the Beijer Foundation, Sweden.

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Authors and Affiliations

  1. Department of Genetics and Pathology, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden

    E L Ivansson, J J Magnusson & U B Gyllensten

  2. Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden

    P K E Magnusson

  3. Department of Human Genetics, Roche Molecular Systems, Alameda, CA, USA

    H A Erlich

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  1. E L Ivansson
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  2. J J Magnusson
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Correspondence to U B Gyllensten.

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Henry Erlich is employed by Roche Molecular Systems who provided reagents for genotyping.

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Ivansson, E., Magnusson, J., Magnusson, P. et al. MHC loci affecting cervical cancer risk: distinguishing the effects of HLA-DQB1 and non-HLA genes TNF, LTA, TAP1 and TAP2. Genes Immun 9, 613–623 (2008). https://doi.org/10.1038/gene.2008.58

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