Defining the genetic susceptibility to cervical neoplasia—A genome-wide association study
by Paul J. Leo, Margaret M. Madeleine, Sophia Wang, Stephen M. Schwartz, Felicity Newell, Ulrika Pettersson-Kymmer, Kari Hemminki, Goran Hallmans, Sven Tiews, Winfried Steinberg, Janet S. Rader, Felipe Castro, Mahboobeh Safaeian, Eduardo L. Franco, François Coutlée, Claes Ohlsson, Adrian Cortes, Mhairi Marshall, Pamela Mukhopadhyay, Katie Cremin, Lisa G. Johnson, Suzanne Garland, Sepehr N. Tabrizi, Nicolas Wentzensen, Freddy Sitas, Julian Little, Maggie Cruickshank, Ian H. Frazer, Allan Hildesheim, Matthew A. Brown
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.Publisher URL: http://feeds.plos.org/~r/plosgenetics/NewArticles/~3/3pNXsM94dcA/article
DOI: 10.1371/journal.pgen.1006866
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