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Genome-wide association studies identify susceptibility loci for epithelial ovarian cancer in east Asian women.
Lawrenson, Kate; Song, Fengju; Hazelett, Dennis J; Kar, Siddhartha P; Tyrer, Jonathan; Phelan, Catherine M; Corona, Rosario I; Rodríguez-Malavé, Norma I; Seo, Ji-Hei; Adler, Emily; Coetzee, Simon G; Segato, Felipe; Fonseca, Marcos A S; Amos, Christopher I; Carney, Michael E; Chenevix-Trench, Georgia; Choi, Jiyeob; Doherty, Jennifer A; Jia, Weihua; Jin, Gang J; Kim, Byoung-Gie; Le, Nhu D; Lee, Juyeon; Li, Lian; Lim, Boon K; Adenan, Noor A; Mizuno, Mika; Park, Boyoung; Pearce, Celeste L; Shan, Kang; Shi, Yongyong; Shu, Xiao-Ou; Sieh, Weiva; Thompson, Pamela J; Wilkens, Lynne R; Wei, Qingyi; Woo, Yin L; Yan, Li; Karlan, Beth Y; Freedman, Matthew L; Noushmehr, Houtan; Goode, Ellen L; Berchuck, Andrew; Sellers, Thomas A; Teo, Soo-Hwang; Zheng, Wei; Matsuo, Keitaro; Park, Sue; Chen, Kexin; Pharoah, Paul D P.
Affiliation
  • Lawrenson K; Women's Cancer Program at the Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Suite 290W, Los Angeles, CA, USA; Center for Bioinformatics and Functional Genomics, Cedars Sinai Genomics Core, Cedars-Sinai Medical Center, Los Angeles, CA, USA. Electro
  • Song F; National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China; Department of Epidemiology and Biostatistics, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China.
  • Hazelett DJ; Center for Bioinformatics and Functional Genomics, Cedars Sinai Genomics Core, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
  • Kar SP; Department of Oncology, Centre for Cancer Genetic Epidemiology, University of Cambridge, Strangeways Research Laboratory, Cambridge, UK.
  • Tyrer J; Department of Oncology, Centre for Cancer Genetic Epidemiology, University of Cambridge, Strangeways Research Laboratory, Cambridge, UK.
  • Phelan CM; Department of Gynecologic Oncology, Moffitt Cancer Center, Tampa, FL, USA; Department of Cancer Epidemiology, Moffitt Cancer Center, Tampa, FL, USA.
  • Corona RI; Women's Cancer Program at the Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Suite 290W, Los Angeles, CA, USA; Center for Bioinformatics and Functional Genomics, Cedars Sinai Genomics Core, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
  • Rodríguez-Malavé NI; Center for Bioinformatics and Functional Genomics, Cedars Sinai Genomics Core, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
  • Seo JH; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
  • Adler E; Department of Preventive Medicine, University of Southern California, Keck School of Medicine, 1450 Biggy Street, Los Angeles, CA, USA.
  • Coetzee SG; Center for Bioinformatics and Functional Genomics, Cedars Sinai Genomics Core, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
  • Segato F; Department of Genetics, Ribeirão Preto Medical School, University of São Paulo, 14049-900, Brazil.
  • Fonseca MAS; Department of Genetics, Ribeirão Preto Medical School, University of São Paulo, 14049-900, Brazil.
  • Amos CI; Institute for Clinical and Translational Research, Department of Medicine, Baylor School of Medicine, Houston,TX, USA.
  • Carney ME; Department of Obstetrics and Gynecology, John A. Burns School of Medicine, University of Hawaii, Honolulu, HI, USA.
  • Chenevix-Trench G; Genetics and Computational Biology Department, QIMR Berghofer Medical Research Institute, 300 Herston Road, Herston, QLD 4006, Australia.
  • Choi J; Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea; Cancer Research Institute, Seoul National University, Seoul, Republic of Korea; Department of Biomedical Science, Graduate School, Seoul National University, Seoul, Republic of Korea.
  • Doherty JA; Jon M. and Karen Huntsman Endowed Associate Professor in Cancer Research Huntsman Cancer Institute, Department of Population Health Sciences, University of Utah, USA.
  • Jia W; State Key Laboratory of Oncology in Southern China, Cancer Center, Sun Yat-sen University, Guangzhou, Guangdong 510060, China.
  • Jin GJ; ShanghaiBio Corporation, Shanghai, China; CloudHealth Genomics Ltd, Shanghai, China.
  • Kim BG; Department of Obstetrics and Gynecology, Samsung Medical Center, Sungkyunkwan University, School of Medicine, Republic of Korea.
  • Le ND; Cancer Control Research, BC Cancer Agency, Vancouver, BC, Canada.
  • Lee J; Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea; Department of Biomedical Science, Graduate School, Seoul National University, 103 Daehak-ro, Jongno-gu, Seoul 110-799, Republic of Korea.
  • Li L; National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China; Department of Epidemiology and Biostatistics, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China.
  • Lim BK; The Department of Obstetrics and Gynaecology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
  • Adenan NA; The Department of Obstetrics and Gynaecology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
  • Mizuno M; Department of Gynecological Oncology, Aichi Cancer Center Hospital, Japan.
  • Park B; Department of Preventive Medicine, College of Medicine, Hanyang, Seoul, Republic of Korea.
  • Pearce CL; Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor, MI, USA.
  • Shan K; Department of Obstetrics and Gynaecology,Hebei Medical University, Fourth Hospital, Shijiazhuang, China.
  • Shi Y; Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Ministry of Education, Shanghai Jiao Tong University, Shanghai, China.
  • Shu XO; Division of Epidemiology, Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN, USA.
  • Sieh W; Department of Population Health Science and Policy, Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Thompson PJ; Cancer Prevention and Control, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
  • Wilkens LR; Cancer Epidemiology Program, University of Hawaii Cancer Center, HI, USA.
  • Wei Q; Cancer Institute, Fudan University Shanghai Cancer Center, Shanghai 200032, China; Duke Cancer Institute, Duke University Medical Center, Durham, NC 27710, USA.
  • Woo YL; The Department of Obstetrics and Gynaecology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
  • Yan L; Department of Molecular Biology, Hebei Medical University, Fourth Hospital, Shijiazhuang, China.
  • Karlan BY; Women's Cancer Program at the Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Suite 290W, Los Angeles, CA, USA.
  • Freedman ML; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
  • Noushmehr H; Department of Genetics, Ribeirão Preto Medical School, University of São Paulo, 14049-900, Brazil; Department of Neurosurgery, Henry Ford Health System, Detroit, MI, USA.
  • Goode EL; Department of Health Science Research, Division of Epidemiology, Mayo Clinic, Rochester, MN, USA.
  • Berchuck A; Department of Obstetrics and Gynecology, Duke University Medical Center, Durham, NC, USA.
  • Sellers TA; Department of Cancer Epidemiology, Moffitt Cancer Center, Tampa, FL, USA.
  • Teo SH; Cancer Research Initiatives Foundation, Subang Jaya, Selangor, Malaysia.
  • Zheng W; Division of Epidemiology, Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN, USA.
  • Matsuo K; Division of Molecular and Clinical Epidemiology, Aichi Cancer Center Research Institute, Japan.
  • Park S; Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea; Cancer Research Institute, Seoul National University, Seoul, Republic of Korea; Department of Biomedical Science, Graduate School, Seoul National University, Seoul, Republic of Korea.
  • Chen K; National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China; Department of Epidemiology and Biostatistics, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China.
  • Pharoah PDP; Department of Oncology, Centre for Cancer Genetic Epidemiology, University of Cambridge, Strangeways Research Laboratory, Cambridge, UK; Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Strangeways Research Laboratory, Worts Causeway, Cam
Gynecol Oncol ; 153(2): 343-355, 2019 05.
Article in En | MEDLINE | ID: mdl-30898391
ABSTRACT

OBJECTIVE:

Genome-wide association studies (GWASs) for epithelial ovarian cancer (EOC) have focused largely on populations of European ancestry. We aimed to identify common germline variants associated with EOC risk in Asian women.

METHODS:

Genotyping was performed as part of the OncoArray project. Samples with >60% Asian ancestry were included in the analysis. Genotyping was performed on 533,631 SNPs in 3238 Asian subjects diagnosed with invasive or borderline EOC and 4083 unaffected controls. After imputation, genotypes were available for 11,595,112 SNPs to identify associations.

RESULTS:

At chromosome 6p25.2, SNP rs7748275 was associated with risk of serous EOC (odds ratio [OR] = 1.34, P = 8.7 × 10-9) and high-grade serous EOC (HGSOC) (OR = 1.34, P = 4.3 × 10-9). SNP rs6902488 at 6p25.2 (r2 = 0.97 with rs7748275) lies in an active enhancer and is predicted to impact binding of STAT3, P300 and ELF1. We identified additional risk loci with low Bayesian false discovery probability (BFDP) scores, indicating they are likely to be true risk associations (BFDP <10%). At chromosome 20q11.22, rs74272064 was associated with HGSOC risk (OR = 1.27, P = 9.0 × 10-8). Overall EOC risk was associated with rs10260419 at chromosome 7p21.3 (OR = 1.33, P = 1.2 × 10-7) and rs74917072 at chromosome 2q37.3 (OR = 1.25, P = 4.7 × 10-7). At 2q37.3, expression quantitative trait locus analysis in 404 HGSOC tissues identified ESPNL as a putative candidate susceptibility gene (P = 1.2 × 10-7).

CONCLUSION:

While some risk loci were shared between East Asian and European populations, others were population-specific, indicating that the landscape of EOC risk in Asian women has both shared and unique features compared to women of European ancestry.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Carcinoma, Ovarian Epithelial Type of study: Observational_studies / Prognostic_studies / Risk_factors_studies Limits: Female / Humans Language: En Journal: Gynecol Oncol Year: 2019 Document type: Article
Fulltext
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Carcinoma, Ovarian Epithelial Type of study: Observational_studies / Prognostic_studies / Risk_factors_studies Limits: Female / Humans Language: En Journal: Gynecol Oncol Year: 2019 Document type: Article