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@article{Bowden:2021:10.1016/S1470-2045(21)00028-0,
author = {Bowden, S and Bodinier, B and Kalliala, I and Zuber, V and Vuckovic, D and Doulgeraki, T and Whitaker, M and Wielscher, M and Cartwright, R and Tsilidis, K and Bennett, P and Jarvelin, M-R and Flanagan, J and Chadeau, M and Kyrgiou, M and FinnGen, consortium},
doi = {10.1016/S1470-2045(21)00028-0},
journal = {The Lancet Oncology},
pages = {548--557},
title = {Genetic variation in cervical preinvasive and invasive disease: a genome-wide association study},
url = {http://dx.doi.org/10.1016/S1470-2045(21)00028-0},
volume = {22},
year = {2021}
}

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TY  - JOUR
AB  - Background: Most uterine cervical high-risk HPV infections (hrHPV) are transient, with only a small 3fraction developing into cervical cancer. Family aggregation studies and heritability estimates suggest 4a  significant  inherited  genetic  component. Candidate  gene  studies  and  previous  genome-wide 5association  studies  (GWAS)  report  associations between  the  human  leukocyte  antigen  (HLA)  region 6and cervical cancer. 78Methods: Adopting  a  genome-wide  approach,  we  compared  the  genetic  variation  in  women  with 9invasive cervical cancer (ICC) and cervical intra-epithelial neoplasia (CIN) grade 3, to that in healthy 10controls using the largest reported cohort of unrelated European individuals (N=150,314)to date. We 11sought for replication in a second large independent dataset (N=128,123). We further performed a two-12sample  Mendelian  Randomisation  approach  to  explore  the  role  of  risk  factors  in  the  genetic  risk  of 13cervical cancer.1415Findings: In our analysis (N=4,769 CIN3 and ICC cases; N=145,545 controls), of the (N=9,600,464) 16assayed and imputed SNPs, six independent variants were found associated with CIN3and ICC. These 17included  novel  loci  rs10175462(PAX8;  OR=0.87(95%CI=0.84-0.91); P=1.07x10-9)  and  rs27069 18(CLPTM1L;OR=0.88(95%CI=0.84-0.92); P=2.51x10-9), and previously reported signals at rs9272050 19(HLA-DQA1;OR=1.27(95%CI=1.21-1.32); P=2.51x10-28),     rs6938453     (MICA;OR=0.7920(95%CI=0.75-0.83); P=1.97x10-17), rs55986091    (HLA-DQB1;OR=0.66(95%CI=0.60-0.72); 21P=6.42x10-22)   and   rs9266183   (HLA-B;OR=0.73(95%CI=0.64-0.83); P=1.53x10-6). Mendelian 22randomisation further supported the complementary role of smoking, age at first pregnancy, and number 23of sexual partners in the risk of developing cervical cancer.2425Interpretation: Our results provide substantial new evidence for genetic susceptibility to cervical cancer, 26including PAX8, CLPTM1LandHLA genes, suggesting disruption in apoptotic and immun
AU  - Bowden,S
AU  - Bodinier,B
AU  - Kalliala,I
AU  - Zuber,V
AU  - Vuckovic,D
AU  - Doulgeraki,T
AU  - Whitaker,M
AU  - Wielscher,M
AU  - Cartwright,R
AU  - Tsilidis,K
AU  - Bennett,P
AU  - Jarvelin,M-R
AU  - Flanagan,J
AU  - Chadeau,M
AU  - Kyrgiou,M
AU  - FinnGen,consortium
DO  - 10.1016/S1470-2045(21)00028-0
EP  - 557
PY  - 2021///
SN  - 1213-9432
SP  - 548
TI  - Genetic variation in cervical preinvasive and invasive disease: a genome-wide association study
T2  - The Lancet Oncology
UR  - http://dx.doi.org/10.1016/S1470-2045(21)00028-0
UR  - https://www.sciencedirect.com/science/article/pii/S1470204521000280
UR  - http://hdl.handle.net/10044/1/86837
VL  - 22
ER  -

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