Ερευνητικό υλικό ΕΚΠΑ

Identification of a novel susceptibility locus at 13q34 and refinement
of the 20p12.2 region as a multi-signal locus associated with bladder
cancer risk in individuals of European ancestry

Αγγλικά

Candidate gene and genome-wide association studies (GWAS) have
identified 15 independent genomic regions associated with bladder cancer
risk. In search for additional susceptibility variants, we followed up
on four promising single-nucleotide polymorphisms (SNPs) that had not
achieved genome-wide significance in 6911 cases and 11 814 controls
(rs6104690, rs4510656, rs5003154 and rs4907479, P < 1x 10(-6)), using
additional data from existing GWAS datasets and targeted genotyping for
studies that did not have GWAS data. In a combined analysis, which
included data on up to 15 058 cases and 286 270 controls, two SNPs
achieved genome-wide statistical significance: rs6104690 in a gene
desert at 20p12.2 (P = 2.19 x 10(-11)) and rs4907479 within the MCF2L
gene at 13q34 (P = 3.3 x 10(-10)). Imputation and fine-mapping analyses
were performed in these two regions for a subset of 5551 bladder cancer
cases and 10 242 controls. Analyses at the 13q34 region suggest a single
signal marked by rs4907479. In contrast, we detected two signals in the
20p12.2 region-the first signal is marked by rs6104690, and the second
signal is marked by two moderately correlated SNPs (r(2) = 0.53),
rs6108803 and the previously reported rs62185668. The second 20p12.2
signal is more strongly associated with the risk of muscle-invasive
(T2-T4 stage) compared with non-muscle-invasive (Ta, T1 stage) bladder
cancer (case-case P <= 0.02 for both rs62185668 and rs6108803).
Functional analyses are needed to explore the biological mechanisms
underlying these novel genetic associations with risk for bladder
cancer.

2016

Figueroa, Jonine D.
Middlebrooks, Candace D.
Banday, A. Rouf and
Ye, Yuanqing
Garcia-Closas, Montserrat
Chatterjee, Nilanjan and
Koutros, Stella
Kiemeney, Lambertus A.
Rafnar, Thorunn and
Bishop, Timothy
Furberg, Helena
Matullo, Giuseppe
Golka,
Klaus
Gago-Dominguez, Manuela
Taylor, Jack A.
Fletcher, Tony
and Siddiq, Afshan
Cortessis, Victoria K.
Kooperberg, Charles
and Cussenot, Olivier
Benhamou, Simone
Prescott, Jennifer and
Porru, Stefano
Dinney, Colin P.
Malats, Nuria
Baris, Dalsu
and Purdue, Mark P.
Jacobs, Eric J.
Albanes, Demetrius
Wang,
Zhaoming
Chung, Charles C.
Vermeulen, Sita H.
Aben, Katja K.
and Galesloot, Tessel E.
Thorleifsson, Gudmar
Sulem, Patrick and
Stefansson, Kari
Kiltie, Anne E.
Harland, Mark
Teo, Mark and
Offit, Kenneth
Vijai, Joseph
Bajorin, Dean
Kopp, Ryan and
Fiorito, Giovanni
Guarrera, Simonetta
Sacerdote, Carlotta and
Selinski, Silvia
Hengstler, Jan G.
Gerullis, Holger and
Ovsiannikov, Daniel
Blaszkewicz, Meinolf
Esteban Castelao, Jose
and Calaza, Manuel
Martinez, Maria Elena
Cordeiro, Patricia and
Xu, Zongli
Panduri, Vijayalakshmi
Kumar, Rajiv
Gurzau,
Eugene
Koppova, Kvetoslava
Bueno-De-Mesquita, H. Bas and
Ljungberg, Borje
Clavel-Chapelon, Francoise
Weiderpass,
Elisabete
Krogh, Vittorio
Dorronsoro, Miren
Travis, Ruth C.
and Tjonneland, Anne
Brennan, Paul
Chang-Claude, Jenny and
Riboli, Elio
Conti, David
Stern, Marianna C.
Pike, Malcolm
C.
Van den Berg, David
Yuan, Jian-Min
Hohensee, Chancellor
and Jeppson, Rebecca P.
Cancel-Tassin, Geraldine
Roupret, Morgan
and Comperat, Eva
Turman, Constance
De Vivo, Immaculata and
Giovannucci, Edward
Hunter, David J.
Kraft, Peter
Lindstrom,
Sara
Carta, Angela
Pavanello, Sofia
Arici, Cecilia and
Mastrangelo, Giuseppe
Kamat, Ashish M.
Zhang, Liren
Gong,
Yilei
Pu, Xia
Hutchinson, Amy
Burdett, Laurie
Wheeler,
William A.
Karagas, Margaret R.
Johnson, Alison
Schned, Alan
and Hosain, G. M. Monawar
Schwenn, Molly
Kogevinas, Manolis and
Tardon, Adonina
Serra, Consol
Carrato, Alfredo and
Garcia-Closas, Reina
Lloreta, Josep
Andriole, Jr., Gerald and
Grubb, III, Robert
Black, Amanda
Diver, W. Ryan
Gapstur,
Susan M.
Weinstein, Stephanie
Virtamo, Jarmo
Haiman,
Christopher A.
Landi, Maria Teresa
Caporaso, Neil E. and
Fraumeni, Jr., Joseph F.
Vineis, Paolo
Wu, Xifeng
Chanock,
Stephen J.
Silverman, Debra T.
Prokunina-Olsson, Ludmila and
Rothman, Nathaniel

Human Molecular Genetics

Oxford University Press

25

6

1203-1214

https://doi.org/10.1093/hmg/ddv492

10.1093/hmg/ddv492

https://pergamos.lib.uoa.gr/uoa/dl/object/3169519