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

Leo, Paul J; Madeleine, Margaret M.; Wang, Sophia S; Schwartz, Stephen M.; Newell, Felicity S.; Pettersson-Kymmer, Ulrika; Hemminki, Kari LU ; Hallmans, Goran; Tiews, Sven and Steinberg, Winfried, et al. (2017) In PLoS Genetics 13(8).
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... (More)

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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@article{b3457f9d-7d1b-49f3-b681-0330ee37ede0,
  abstract     = {<p>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 &gt;7.1% risk, and those in the highest 5% have approximately &gt;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.</p>},
  articleno    = {e1006866},
  author       = {Leo, Paul J and Madeleine, Margaret M. and Wang, Sophia S and Schwartz, Stephen M. and Newell, Felicity S. and Pettersson-Kymmer, Ulrika and Hemminki, Kari and Hallmans, Goran and Tiews, Sven and Steinberg, Winfried and Rader, Janet S. and Castro, Felipe A and Safaeian, Mahboobeh and Franco, Eduardo L. and Coutlée, François and Ohlsson, Claes and Cortes, Adrian and Marshall, Mhairi and Mukhopadhyay, Pamela and Cremin, Katie and Johnson, Lisa G. and Garland, Suzanne M and Tabrizi, Sepehr N. and Wentzensen, Nicolas and Sitas, Freddy and Little, Julian and Cruickshank, Maggie and Frazer, Ian H. and Hildesheim, Allan and Brown, Matthew A},
  issn         = {1553-7390},
  keyword      = {GWAS,cervical neoplasia, genetic susceptibility },
  language     = {eng},
  month        = {08},
  number       = {8},
  publisher    = {Public Library of Science},
  series       = {PLoS Genetics},
  title        = {Defining the genetic susceptibility to cervical neoplasia—A genome-wide association study},
  url          = {http://dx.doi.org/10.1371/journal.pgen.1006866},
  volume       = {13},
  year         = {2017},
}