Defining the Genetic Susceptibility to Cervical Neoplasia-A Genome-wide Association Study

Overview

Journal PLoS Genet

Specialty Genetics

Date 2017 Aug 15

PMID 28806749

Citations 56

Authors

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

Francois Coutlee

Claes Ohlsson

Adrian Cortes

Mhairi Marshall

Pamela Mukhopadhyay

Katie Cremin

Lisa G Johnson

Cornelia L Trimble

Suzanne Garland

Sepehr N Tabrizi

Nicolas Wentzensen

Freddy Sitas

Julian Little

Maggie Cruickshank

Ian H Frazer

Allan Hildesheim

Matthew A Brown

Affiliations

Soon will be listed here.

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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