Genome-wide association study identifies new susceptibility loci for epithelial ovarian cancer in Han Chinese women

Kexin Chen; Hongxia Ma; Lian Li; Rongyu Zang; Cheng Wang; Fengju Song; Tingyan Shi; Dianke Yu; Ming Yang; Wenqiong Xue; Juncheng Dai; Shuang Li; Hong Zheng; Chen Wu; Ying Zhang; Xiaohua Wu; Dake Li; Fengxia Xue; Haixin Li; Zhi Jiang; Jibin Liu; Yuexin Liu; Pei Li; Wen Tan; Jing Han; Jiang Jie; Quan Hao; Zhibin Hu; Dongxin Lin; Ding Ma; Weihua Jia; Hongbing Shen; Qingyi Wei

doi:10.1038/ncomms5682

Genome-wide association study identifies new susceptibility loci for epithelial ovarian cancer in Han Chinese women

Nat Commun. 2014 Aug 19:5:4682. doi: 10.1038/ncomms5682.

Authors

Kexin Chen¹, Hongxia Ma², Lian Li¹, Rongyu Zang³, Cheng Wang⁴, Fengju Song⁵, Tingyan Shi⁶, Dianke Yu⁷, Ming Yang⁸, Wenqiong Xue⁹, Juncheng Dai⁴, Shuang Li¹⁰, Hong Zheng⁵, Chen Wu⁷, Ying Zhang⁹, Xiaohua Wu¹¹, Dake Li¹², Fengxia Xue¹³, Haixin Li⁵, Zhi Jiang¹⁴, Jibin Liu¹⁵, Yuexin Liu¹⁶, Pei Li⁵, Wen Tan⁷, Jing Han⁴, Jiang Jie⁴, Quan Hao¹⁷, Zhibin Hu⁴, Dongxin Lin⁷, Ding Ma¹⁰, Weihua Jia⁹, Hongbing Shen⁴, Qingyi Wei¹⁸

Affiliations

¹ 1] Department of Epidemiology and Biostatistics, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy of Tianjin, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, China [2].
² 1] State Key Laboratory of Reproductive Medicine, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, School of Public Health, Nanjing Medical University, Nanjing 211166, China [2].
³ 1] Department of Gynecologic Oncology, Fudan University Shanghai Cancer Center, Shanghai 200032, China [2].
⁴ State Key Laboratory of Reproductive Medicine, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, School of Public Health, Nanjing Medical University, Nanjing 211166, China.
⁵ Department of Epidemiology and Biostatistics, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy of Tianjin, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, China.
⁶ 1] Department of Gynecologic Oncology, Fudan University Shanghai Cancer Center, Shanghai 200032, China [2] Cancer Institute, Fudan University Shanghai Cancer Center, Shanghai 200032, China.
⁷ Department of Etiology and Carcinogenesis, Cancer Institute and Hospital, Chinese Academy of Medical Sciences, Beijing 100021, China.
⁸ College of Life Science and Technology, Beijing University of Chemical Technology, Beijing 100029, China.
⁹ State Key Laboratory of Oncology in Southern China, Cancer Center, Sun Yat-sen University, Guangzhou, Guangdong 510060, China.
¹⁰ Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China.
¹¹ Department of Gynecologic Oncology, Fudan University Shanghai Cancer Center, Shanghai 200032, China.
¹² Department of Gynecology, Jiangsu Province Hospital of TCM, Affiliated Hospital of Nanjing University of TCM, Nanjing 210029, China.
¹³ Department of Gynecology and Obstetrics, Tianjin Medical University General Hospital, Tianjin 300052, China.
¹⁴ Department of Gynecologic Surgery, Jiangsu Cancer Hospital, Nanjing Medical University, Nanjing, Jiangsu 210009, China.
¹⁵ Department of Tissue Bank, Nantong Tumor Hospital, Nantong, Jiangsu 226361, China.
¹⁶ Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
¹⁷ Department of Urology, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, China.
¹⁸ 1] Cancer Institute, Fudan University Shanghai Cancer Center, Shanghai 200032, China [2] Duke Cancer Institute, Duke University Medical Center, Durham, North Carolina 27710, USA.

PMID: 25134534
DOI: 10.1038/ncomms5682

Abstract

Ovarian cancer is the leading cause of death from gynaecological malignancies worldwide. Here we perform a three-stage genome-wide association study (GWAS) in Han Chinese women to identify risk genetic variants for epithelial ovarian cancer (EOC). We scan 900,015 single-nucleotide polymorphisms (SNPs) in 1,057 EOC cases and 1,191 controls in stage I, and replicate 41 SNPs (P(meta)<10(-4)) in 960 EOC cases and 1,799 controls (stage II), and an additional 492 EOC cases and 1,004 controls (stage III). Finally, we identify two EOC susceptibility loci at 9q22.33 (rs1413299 in COL15A1, P(meta) = 1.88 × 10(-8)) and 10p11.21 (rs1192691 near ANKRD30A, P(meta) = 2.62 × 10(-8)), and two consistently replicated loci at 12q14.2 (rs11175194 in SRGAP1, P(meta) = 1.14 × 10(-7)) and 9q34.2 (rs633862 near ABO and SURF6, P(meta) = 8.57 × 10(-7)) (P<0.05 in all three stages). These results may advance our understanding of genetic susceptibility to EOC.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Asian People / genetics*
Carcinoma, Ovarian Epithelial
Case-Control Studies
Collagen / genetics
Female
GTPase-Activating Proteins / genetics
Genetic Loci / genetics*
Genetic Predisposition to Disease / ethnology
Genetic Predisposition to Disease / genetics*
Genome-Wide Association Study*
Humans
Middle Aged
Neoplasms, Glandular and Epithelial / ethnology
Neoplasms, Glandular and Epithelial / genetics*
Nuclear Proteins / genetics
Ovarian Neoplasms / ethnology
Ovarian Neoplasms / genetics*
Polymorphism, Single Nucleotide / genetics
Protein Serine-Threonine Kinases / genetics
Risk Factors

Substances

COL15A1 protein, human
GTPase-Activating Proteins
Nuclear Proteins
SRGAP1 protein, human
SURF6 protein, human
Collagen
RIPK4 protein, human
Protein Serine-Threonine Kinases