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Identification of 12 new susceptibility loci for different histotypes of epithelial ovarian cancer.


ABSTRACT: To identify common alleles associated with different histotypes of epithelial ovarian cancer (EOC), we pooled data from multiple genome-wide genotyping projects totaling 25,509 EOC cases and 40,941 controls. We identified nine new susceptibility loci for different EOC histotypes: six for serous EOC histotypes (3q28, 4q32.3, 8q21.11, 10q24.33, 18q11.2 and 22q12.1), two for mucinous EOC (3q22.3 and 9q31.1) and one for endometrioid EOC (5q12.3). We then performed meta-analysis on the results for high-grade serous ovarian cancer with the results from analysis of 31,448 BRCA1 and BRCA2 mutation carriers, including 3,887 mutation carriers with EOC. This identified three additional susceptibility loci at 2q13, 8q24.1 and 12q24.31. Integrated analyses of genes and regulatory biofeatures at each locus predicted candidate susceptibility genes, including OBFC1, a new candidate susceptibility gene for low-grade and borderline serous EOC.

SUBMITTER: Phelan CM 

PROVIDER: S-EPMC5612337 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature

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Identification of 12 new susceptibility loci for different histotypes of epithelial ovarian cancer.

Phelan Catherine M CM   Kuchenbaecker Karoline B KB   Tyrer Jonathan P JP   Kar Siddhartha P SP   Lawrenson Kate K   Winham Stacey J SJ   Dennis Joe J   Pirie Ailith A   Riggan Marjorie J MJ   Chornokur Ganna G   Earp Madalene A MA   Lyra Paulo C PC   Lee Janet M JM   Coetzee Simon S   Beesley Jonathan J   McGuffog Lesley L   Soucy Penny P   Dicks Ed E   Lee Andrew A   Barrowdale Daniel D   Lecarpentier Julie J   Leslie Goska G   Aalfs Cora M CM   Aben Katja K H KKH   Adams Marcia M   Adlard Julian J   Andrulis Irene L IL   Anton-Culver Hoda H   Antonenkova Natalia N   Aravantinos Gerasimos G   Arnold Norbert N   Arun Banu K BK   Arver Brita B   Azzollini Jacopo J   Balmaña Judith J   Banerjee Susana N SN   Barjhoux Laure L   Barkardottir Rosa B RB   Bean Yukie Y   Beckmann Matthias W MW   Beeghly-Fadiel Alicia A   Benitez Javier J   Bermisheva Marina M   Bernardini Marcus Q MQ   Birrer Michael J MJ   Bjorge Line L   Black Amanda A   Blankstein Kenneth K   Blok Marinus J MJ   Bodelon Clara C   Bogdanova Natalia N   Bojesen Anders A   Bonanni Bernardo B   Borg Åke Å   Bradbury Angela R AR   Brenton James D JD   Brewer Carole C   Brinton Louise L   Broberg Per P   Brooks-Wilson Angela A   Bruinsma Fiona F   Brunet Joan J   Buecher Bruno B   Butzow Ralf R   Buys Saundra S SS   Caldes Trinidad T   Caligo Maria A MA   Campbell Ian I   Cannioto Rikki R   Carney Michael E ME   Cescon Terence T   Chan Salina B SB   Chang-Claude Jenny J   Chanock Stephen S   Chen Xiao Qing XQ   Chiew Yoke-Eng YE   Chiquette Jocelyne J   Chung Wendy K WK   Claes Kathleen B M KBM   Conner Thomas T   Cook Linda S LS   Cook Jackie J   Cramer Daniel W DW   Cunningham Julie M JM   D'Aloisio Aimee A AA   Daly Mary B MB   Damiola Francesca F   Damirovna Sakaeva Dina SD   Dansonka-Mieszkowska Agnieszka A   Dao Fanny F   Davidson Rosemarie R   DeFazio Anna A   Delnatte Capucine C   Doheny Kimberly F KF   Diez Orland O   Ding Yuan Chun YC   Doherty Jennifer Anne JA   Domchek Susan M SM   Dorfling Cecilia M CM   Dörk Thilo T   Dossus Laure L   Duran Mercedes M   Dürst Matthias M   Dworniczak Bernd B   Eccles Diana D   Edwards Todd T   Eeles Ros R   Eilber Ursula U   Ejlertsen Bent B   Ekici Arif B AB   Ellis Steve S   Elvira Mingajeva M   Eng Kevin H KH   Engel Christoph C   Evans D Gareth DG   Fasching Peter A PA   Ferguson Sarah S   Ferrer Sandra Fert SF   Flanagan James M JM   Fogarty Zachary C ZC   Fortner Renée T RT   Fostira Florentia F   Foulkes William D WD   Fountzilas George G   Fridley Brooke L BL   Friebel Tara M TM   Friedman Eitan E   Frost Debra D   Ganz Patricia A PA   Garber Judy J   García María J MJ   Garcia-Barberan Vanesa V   Gehrig Andrea A   Gentry-Maharaj Aleksandra A   Gerdes Anne-Marie AM   Giles Graham G GG   Glasspool Rosalind R   Glendon Gord G   Godwin Andrew K AK   Goldgar David E DE   Goranova Teodora T   Gore Martin M   Greene Mark H MH   Gronwald Jacek J   Gruber Stephen S   Hahnen Eric E   Haiman Christopher A CA   Håkansson Niclas N   Hamann Ute U   Hansen Thomas V O TVO   Harrington Patricia A PA   Harris Holly R HR   Hauke Jan J   Hein Alexander A   Henderson Alex A   Hildebrandt Michelle A T MAT   Hillemanns Peter P   Hodgson Shirley S   Høgdall Claus K CK   Høgdall Estrid E   Hogervorst Frans B L FBL   Holland Helene H   Hooning Maartje J MJ   Hosking Karen K   Huang Ruea-Yea RY   Hulick Peter J PJ   Hung Jillian J   Hunter David J DJ   Huntsman David G DG   Huzarski Tomasz T   Imyanitov Evgeny N EN   Isaacs Claudine C   Iversen Edwin S ES   Izatt Louise L   Izquierdo Angel A   Jakubowska Anna A   James Paul P   Janavicius Ramunas R   Jernetz Mats M   Jensen Allan A   Jensen Uffe Birk UB   John Esther M EM   Johnatty Sharon S   Jones Michael E ME   Kannisto Päivi P   Karlan Beth Y BY   Karnezis Anthony A   Kast Karin K   Kennedy Catherine J CJ   Khusnutdinova Elza E   Kiemeney Lambertus A LA   Kiiski Johanna I JI   Kim Sung-Won SW   Kjaer Susanne K SK   Köbel Martin M   Kopperud Reidun K RK   Kruse Torben A TA   Kupryjanczyk Jolanta J   Kwong Ava A   Laitman Yael Y   Lambrechts Diether D   Larrañaga Nerea N   Larson Melissa C MC   Lazaro Conxi C   Le Nhu D ND   Le Marchand Loic L   Lee Jong Won JW   Lele Shashikant B SB   Leminen Arto A   Leroux Dominique D   Lester Jenny J   Lesueur Fabienne F   Levine Douglas A DA   Liang Dong D   Liebrich Clemens C   Lilyquist Jenna J   Lipworth Loren L   Lissowska Jolanta J   Lu Karen H KH   Lubinński Jan J   Luccarini Craig C   Lundvall Lene L   Mai Phuong L PL   Mendoza-Fandiño Gustavo G   Manoukian Siranoush S   Massuger Leon F A G LFAG   May Taymaa T   Mazoyer Sylvie S   McAlpine Jessica N JN   McGuire Valerie V   McLaughlin John R JR   McNeish Iain I   Meijers-Heijboer Hanne H   Meindl Alfons A   Menon Usha U   Mensenkamp Arjen R AR   Merritt Melissa A MA   Milne Roger L RL   Mitchell Gillian G   Modugno Francesmary F   Moes-Sosnowska Joanna J   Moffitt Melissa M   Montagna Marco M   Moysich Kirsten B KB   Mulligan Anna Marie AM   Musinsky Jacob J   Nathanson Katherine L KL   Nedergaard Lotte L   Ness Roberta B RB   Neuhausen Susan L SL   Nevanlinna Heli H   Niederacher Dieter D   Nussbaum Robert L RL   Odunsi Kunle K   Olah Edith E   Olopade Olufunmilayo I OI   Olsson Håkan H   Olswold Curtis C   O'Malley David M DM   Ong Kai-Ren KR   Onland-Moret N Charlotte NC   Orr Nicholas N   Orsulic Sandra S   Osorio Ana A   Palli Domenico D   Papi Laura L   Park-Simon Tjoung-Won TW   Paul James J   Pearce Celeste L CL   Pedersen Inge Søkilde IS   Peeters Petra H M PHM   Peissel Bernard B   Peixoto Ana A   Pejovic Tanja T   Pelttari Liisa M LM   Permuth Jennifer B JB   Peterlongo Paolo P   Pezzani Lidia L   Pfeiler Georg G   Phillips Kelly-Anne KA   Piedmonte Marion M   Pike Malcolm C MC   Piskorz Anna M AM   Poblete Samantha R SR   Pocza Timea T   Poole Elizabeth M EM   Poppe Bruce B   Porteous Mary E ME   Prieur Fabienne F   Prokofyeva Darya D   Pugh Elizabeth E   Pujana Miquel Angel MA   Pujol Pascal P   Radice Paolo P   Rantala Johanna J   Rappaport-Fuerhauser Christine C   Rennert Gad G   Rhiem Kerstin K   Rice Patricia P   Richardson Andrea A   Robson Mark M   Rodriguez Gustavo C GC   Rodríguez-Antona Cristina C   Romm Jane J   Rookus Matti A MA   Rossing Mary Anne MA   Rothstein Joseph H JH   Rudolph Anja A   Runnebaum Ingo B IB   Salvesen Helga B HB   Sandler Dale P DP   Schoemaker Minouk J MJ   Senter Leigha L   Setiawan V Wendy VW   Severi Gianluca G   Sharma Priyanka P   Shelford Tameka T   Siddiqui Nadeem N   Side Lucy E LE   Sieh Weiva W   Singer Christian F CF   Sobol Hagay H   Song Honglin H   Southey Melissa C MC   Spurdle Amanda B AB   Stadler Zsofia Z   Steinemann Doris D   Stoppa-Lyonnet Dominique D   Sucheston-Campbell Lara E LE   Sukiennicki Grzegorz G   Sutphen Rebecca R   Sutter Christian C   Swerdlow Anthony J AJ   Szabo Csilla I CI   Szafron Lukasz L   Tan Yen Y YY   Taylor Jack A JA   Tea Muy-Kheng MK   Teixeira Manuel R MR   Teo Soo-Hwang SH   Terry Kathryn L KL   Thompson Pamela J PJ   Thomsen Liv Cecilie Vestrheim LCV   Thull Darcy L DL   Tihomirova Laima L   Tinker Anna V AV   Tischkowitz Marc M   Tognazzo Silvia S   Toland Amanda Ewart AE   Tone Alicia A   Trabert Britton B   Travis Ruth C RC   Trichopoulou Antonia A   Tung Nadine N   Tworoger Shelley S SS   van Altena Anne M AM   Van Den Berg David D   van der Hout Annemarie H AH   van der Luijt Rob B RB   Van Heetvelde Mattias M   Van Nieuwenhuysen Els E   van Rensburg Elizabeth J EJ   Vanderstichele Adriaan A   Varon-Mateeva Raymonda R   Vega Ana A   Edwards Digna Velez DV   Vergote Ignace I   Vierkant Robert A RA   Vijai Joseph J   Vratimos Athanassios A   Walker Lisa L   Walsh Christine C   Wand Dorothea D   Wang-Gohrke Shan S   Wappenschmidt Barbara B   Webb Penelope M PM   Weinberg Clarice R CR   Weitzel Jeffrey N JN   Wentzensen Nicolas N   Whittemore Alice S AS   Wijnen Juul T JT   Wilkens Lynne R LR   Wolk Alicja A   Woo Michelle M   Wu Xifeng X   Wu Anna H AH   Yang Hannah H   Yannoukakos Drakoulis D   Ziogas Argyrios A   Zorn Kristin K KK   Narod Steven A SA   Easton Douglas F DF   Amos Christopher I CI   Schildkraut Joellen M JM   Ramus Susan J SJ   Ottini Laura L   Goodman Marc T MT   Park Sue K SK   Kelemen Linda E LE   Risch Harvey A HA   Thomassen Mads M   Offit Kenneth K   Simard Jacques J   Schmutzler Rita Katharina RK   Hazelett Dennis D   Monteiro Alvaro N AN   Couch Fergus J FJ   Berchuck Andrew A   Chenevix-Trench Georgia G   Goode Ellen L EL   Sellers Thomas A TA   Gayther Simon A SA   Antoniou Antonis C AC   Pharoah Paul D P PDP  

Nature genetics 20170327 5


To identify common alleles associated with different histotypes of epithelial ovarian cancer (EOC), we pooled data from multiple genome-wide genotyping projects totaling 25,509 EOC cases and 40,941 controls. We identified nine new susceptibility loci for different EOC histotypes: six for serous EOC histotypes (3q28, 4q32.3, 8q21.11, 10q24.33, 18q11.2 and 22q12.1), two for mucinous EOC (3q22.3 and 9q31.1) and one for endometrioid EOC (5q12.3). We then performed meta-analysis on the results for hi  ...[more]

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