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A genome-wide association study identifies susceptibility loci for ovarian cancer at 2q31 and 8q24.

ABSTRACT: Ovarian cancer accounts for more deaths than all other gynecological cancers combined. To identify common low-penetrance ovarian cancer susceptibility genes, we conducted a genome-wide association study of 507,094 SNPs in 1,768 individuals with ovarian cancer (cases) and 2,354 controls, with follow up of 21,955 SNPs in 4,162 cases and 4,810 controls, leading to the identification of a confirmed susceptibility locus at 9p22 (in BNC2). Here, we report on nine additional candidate loci (defined as having P ? 10??) identified after stratifying cases by histology, which we genotyped in an additional 4,353 cases and 6,021 controls. We confirmed two new susceptibility loci with P ? 5 × 10?? (8q24, P = 8.0 × 10?¹? and 2q31, P = 3.8 × 10?¹?) and identified two additional loci that approached genome-wide significance (3q25, P = 7.1 × 10?? and 17q21, P = 1.4 × 10??). The associations of these loci with serous ovarian cancer were generally stronger than with other cancer subtypes. Analysis of HOXD1, MYC, TIPARP and SKAP1 at these loci and of BNC2 at 9p22 supports a functional role for these genes in ovarian cancer development.

SUBMITTER: Goode EL 

PROVIDER: S-EPMC3020231 | biostudies-literature | 2010 Oct

REPOSITORIES: biostudies-literature

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A genome-wide association study identifies susceptibility loci for ovarian cancer at 2q31 and 8q24.

Goode Ellen L EL   Chenevix-Trench Georgia G   Song Honglin H   Ramus Susan J SJ   Notaridou Maria M   Lawrenson Kate K   Widschwendter Martin M   Vierkant Robert A RA   Larson Melissa C MC   Kjaer Susanne K SK   Birrer Michael J MJ   Berchuck Andrew A   Schildkraut Joellen J   Tomlinson Ian I   Kiemeney Lambertus A LA   Cook Linda S LS   Gronwald Jacek J   Garcia-Closas Montserrat M   Gore Martin E ME   Campbell Ian I   Whittemore Alice S AS   Sutphen Rebecca R   Phelan Catherine C   Anton-Culver Hoda H   Pearce Celeste Leigh CL   Lambrechts Diether D   Rossing Mary Anne MA   Chang-Claude Jenny J   Moysich Kirsten B KB   Goodman Marc T MT   Dörk Thilo T   Nevanlinna Heli H   Ness Roberta B RB   Rafnar Thorunn T   Hogdall Claus C   Hogdall Estrid E   Fridley Brooke L BL   Cunningham Julie M JM   Sieh Weiva W   McGuire Valerie V   Godwin Andrew K AK   Cramer Daniel W DW   Hernandez Dena D   Levine Douglas D   Lu Karen K   Iversen Edwin S ES   Palmieri Rachel T RT   Houlston Richard R   van Altena Anne M AM   Aben Katja K H KK   Massuger Leon F A G LF   Brooks-Wilson Angela A   Kelemen Linda E LE   Le Nhu D ND   Jakubowska Anna A   Lubinski Jan J   Medrek Krzysztof K   Stafford Anne A   Easton Douglas F DF   Tyrer Jonathan J   Bolton Kelly L KL   Harrington Patricia P   Eccles Diana D   Chen Ann A   Molina Ashley N AN   Davila Barbara N BN   Arango Hector H   Tsai Ya-Yu YY   Chen Zhihua Z   Risch Harvey A HA   McLaughlin John J   Narod Steven A SA   Ziogas Argyrios A   Brewster Wendy W   Gentry-Maharaj Aleksandra A   Menon Usha U   Wu Anna H AH   Stram Daniel O DO   Pike Malcolm C MC   Beesley Jonathan J   Webb Penelope M PM   Chen Xiaoqing X   Ekici Arif B AB   Thiel Falk C FC   Beckmann Matthias W MW   Yang Hannah H   Wentzensen Nicolas N   Lissowska Jolanta J   Fasching Peter A PA   Despierre Evelyn E   Amant Frederic F   Vergote Ignace I   Doherty Jennifer J   Hein Rebecca R   Wang-Gohrke Shan S   Lurie Galina G   Carney Michael E ME   Thompson Pamela J PJ   Runnebaum Ingo I   Hillemanns Peter P   Dürst Matthias M   Antonenkova Natalia N   Bogdanova Natalia N   Leminen Arto A   Butzow Ralf R   Heikkinen Tuomas T   Stefansson Kari K   Sulem Patrick P   Besenbacher Sören S   Sellers Thomas A TA   Gayther Simon A SA   Pharoah Paul D P PD  

Nature genetics 20100919 10

Ovarian cancer accounts for more deaths than all other gynecological cancers combined. To identify common low-penetrance ovarian cancer susceptibility genes, we conducted a genome-wide association study of 507,094 SNPs in 1,768 individuals with ovarian cancer (cases) and 2,354 controls, with follow up of 21,955 SNPs in 4,162 cases and 4,810 controls, leading to the identification of a confirmed susceptibility locus at 9p22 (in BNC2). Here, we report on nine additional candidate loci (defined as  ...[more]

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