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    Defining the genetic susceptibility to cervical neoplasia-A genome-wide association study

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    Author
    Leo, PJ; Madeleine, MM; Wang, S; Schwartz, SM; Newell, F; Pettersson-Kymmer, U; Hemminki, K; Hallmans, G; Tiews, S; Steinberg, W; ...
    Date
    2017-08-01
    Source Title
    PLoS Genetics
    Publisher
    PUBLIC LIBRARY SCIENCE
    University of Melbourne Author/s
    Tabrizi, Sepehr; Wark, Suzanne
    Affiliation
    Obstetrics and Gynaecology
    Metadata
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    Document Type
    Journal Article
    Citations
    Leo, P. J., Madeleine, M. M., Wang, S., Schwartz, S. M., Newell, F., Pettersson-Kymmer, U., Hemminki, K., Hallmans, G., Tiews, S., Steinberg, W., Rader, J. S., Castro, F., Safaeian, M., Franco, E. L., Coutlee, F., Ohlsson, C., Cortes, A., Marshall, M., Mukhopadhyay, P. ,... Brown, M. A. (2017). Defining the genetic susceptibility to cervical neoplasia-A genome-wide association study. PLOS GENETICS, 13 (8), https://doi.org/10.1371/journal.pgen.1006866.
    Access Status
    Open Access
    URI
    http://hdl.handle.net/11343/256709
    DOI
    10.1371/journal.pgen.1006866
    Abstract
    A small percentage of women with cervical HPV infection progress to cervical neoplasia, and the risk factors determining progression are incompletely understood. We sought to define the genetic loci involved in cervical neoplasia and to assess its heritability using unbiased unrelated case/control statistical approaches. We demonstrated strong association of cervical neoplasia with risk and protective HLA haplotypes that are determined by the amino-acids carried at positions 13 and 71 in pocket 4 of HLA-DRB1 and position 156 in HLA-B. Furthermore, 36% (standard error 2.4%) of liability of HPV-associated cervical pre-cancer and cancer is determined by common genetic variants. Women in the highest 10% of genetic risk scores have approximately >7.1% risk, and those in the highest 5% have approximately >21.6% risk, of developing cervical neoplasia. Future studies should examine genetic risk prediction in assessing the risk of cervical neoplasia further, in combination with other screening methods.

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