Defining the genetic susceptibility to cervical neoplasia-A genome-wide association study. PLoS Genet 2017 Aug;13(8):e1006866
Date
08/15/2017Pubmed ID
28806749Pubmed Central ID
PMC5570502DOI
10.1371/journal.pgen.1006866Scopus ID
2-s2.0-85028836715 (requires institutional sign-in at Scopus site) 98 CitationsAbstract
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.
Author List
Leo PJ, Madeleine MM, Wang S, Schwartz SM, Newell F, Pettersson-Kymmer U, Hemminki K, Hallmans G, Tiews S, Steinberg W, Rader JS, Castro F, Safaeian M, Franco EL, Coutlée F, Ohlsson C, Cortes A, Marshall M, Mukhopadhyay P, Cremin K, Johnson LG, Trimble CL, Garland S, Tabrizi SN, Wentzensen N, Sitas F, Little J, Cruickshank M, Frazer IH, Hildesheim A, Brown MAAuthor
Janet Sue Rader MD Chair, Professor in the Obstetrics and Gynecology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AllelesCase-Control Studies
Female
Genetic Predisposition to Disease
Genome-Wide Association Study
Genotyping Techniques
HLA-B Antigens
HLA-DRB1 Chains
Haplotypes
Humans
Linkage Disequilibrium
Logistic Models
Major Histocompatibility Complex
Papillomaviridae
Polymorphism, Single Nucleotide
Risk Factors
Uterine Cervical Neoplasms
