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

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 s...

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Bibliographic Details
Published in:PLoS genetics 2017-08, Vol.13 (8), p.e1006866-e1006866
Main Authors: Leo, Paul J, Madeleine, Margaret M, Wang, Sophia, Schwartz, Stephen M, Newell, Felicity, Pettersson-Kymmer, Ulrika, Hemminki, Kari, Hallmans, Goran, Tiews, Sven, Steinberg, Winfried, Rader, Janet S, Castro, Felipe, Safaeian, Mahboobeh, Franco, Eduardo L, Coutlée, François, Ohlsson, Claes, Cortes, Adrian, Marshall, Mhairi, Mukhopadhyay, Pamela, Cremin, Katie, Johnson, Lisa G, Trimble, Cornelia L, Garland, Suzanne, Tabrizi, Sepehr N, Wentzensen, Nicolas, Sitas, Freddy, Little, Julian, Cruickshank, Maggie, Frazer, Ian H, Hildesheim, Allan, Brown, Matthew A
Format: Article
Language:English
Subjects:
Alleles
analysis
Basic Medicine
Biology and Life Sciences
Cancer
Cancer Epidemiology
cancerepidemiologi
Case-Control Studies
Cervical cancer
cervical neoplasia
Cervix
Clinical Medicine
complex traits
comprehensive
Drb1 protein
Epidemiology
familial risks
Female
Genetic Predisposition to Disease
genetic susceptibility
Genetics
Genetics & Heredity
Genome-wide association studies
Genome-Wide Association Study
Genomes
Genotyping Techniques
GWAS
Gynecology
Haplotypes
Health care
Heritability
Histocompatibility antigen HLA
hla-b
HLA-B Antigens - genetics
HLA-DRB1 Chains - genetics
Hospitals
HPV infection
Human papillomavirus
human-papillomavirus infection
Humans
Klinisk medicin
Laboratories
Linkage Disequilibrium
loci
Logistic Models
Major Histocompatibility Complex
Medical and Health Sciences
Medical Genetics
Medical research
Medicin och hälsovetenskap
Medicine and Health Sciences
Medicinsk genetik
Medicinska och farmaceutiska grundvetenskaper
molecular medicine (genetics and pathology)
molekylär medicin (genetik och patologi)
Obstetrics
Papillomaviridae
Polymorphism, Single Nucleotide
Preventive medicine
Public health
Risk Factors
squamous-cell carcinoma
Standard error
Supervision
united-states
Uterine Cervical Neoplasms - diagnosis
Uterine Cervical Neoplasms - genetics
Uterine Cervical Neoplasms - virology
women
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Summary: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.
ISSN:1553-7404
1553-7390
1553-7404
DOI:10.1371/journal.pgen.1006866