Nonsyndromic cleft lip with or without cleft palate and cancer: Evaluation of a possible common genetic background through the analysis of GWAS data

Eva Dunkhase; Kerstin U Ludwig; Michael Knapp; Christine F Skibola; Jane C Figueiredo; Fay Julie Hosking; Eva Ellinghaus; Maria Teresa Landi; Hongxia Ma; Hidewaki Nakagawa; Jong-Won Kim; Jiali Han; Ping Yang; Anne C Böhmer; Manuel Mattheisen; Markus M Nöthen; Elisabeth Mangold

doi:10.1016/j.gdata.2016.08.017

Nonsyndromic cleft lip with or without cleft palate and cancer: Evaluation of a possible common genetic background through the analysis of GWAS data

Genom Data. 2016 Aug 26:10:22-9. doi: 10.1016/j.gdata.2016.08.017. eCollection 2016 Dec.

Authors

Eva Dunkhase¹, Kerstin U Ludwig², Michael Knapp³, Christine F Skibola⁴, Jane C Figueiredo⁵, Fay Julie Hosking⁶, Eva Ellinghaus⁷, Maria Teresa Landi⁸, Hongxia Ma⁹, Hidewaki Nakagawa¹⁰, Jong-Won Kim¹¹, Jiali Han¹², Ping Yang¹³, Anne C Böhmer¹⁴, Manuel Mattheisen¹⁵, Markus M Nöthen², Elisabeth Mangold¹

Affiliations

¹ Institute of Human Genetics, University of Bonn, Sigmund-Freud-Straße 25, 53127 Bonn, Germany.
² Institute of Human Genetics, University of Bonn, Sigmund-Freud-Straße 25, 53127 Bonn, Germany; Department of Genomics, Life and Brain Center, University of Bonn, Sigmund-Freud-Straße 25, 53127 Bonn, Germany.
³ Institute of Medical Biometry, Informatics, and Epidemiology, University of Bonn, Sigmund-Freud-Straße 25, 53127 Bonn, Germany.
⁴ Department of Epidemiology, University of Alabama at Birmingham, 1665 University Boulevard, Birmingham, AL 35294, USA.
⁵ Department of Preventive Medicine, Keck School of Medicine, University of Southern California, 1975 Zonal Ave, Los Angeles, CA 90033, USA.
⁶ Division of Genetics and Epidemiology, The Institute of Cancer Research, 15 Cotswold Road, Sutton SM2 5NG, Surrey, UK.
⁷ Institute of Clinical Molecular Biology, Christian-Albrechts-University Kiel, Schittenhelmstr. 12, 24105 Kiel, Germany.
⁸ National Cancer Institute, NIH, DHHS, 9609 Medical Center Dr, Rockville, MD 20850, USA.
⁹ Department of Epidemiology, School of Public Health, Nanjing Medical University, 140 Hanzhong Rd, Gulou, Nanjing 210029, Jiangsu, China.
¹⁰ Laboratory for Genome Sequencing Analysis, RIKEN Center for Integrative Medical Sciences, 1-7-22 Suehiro-cho, Tsurumi-ku,Yokohama, Kanagawa 230-0045, Japan.
¹¹ Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, (06351) 81 Irwon-Ro Gangnam-gu. Seoul, Republic of Korea.
¹² Department of Epidemiology, Richard M. Fairbanks School of Public Health, Melvin & Bren Simon Cancer Center, Indiana University, 535 Barnhill Dr, Indianapolis, IN 46202, USA.
¹³ Mayo Clinic, 200 First St. SW Rochester, MN 55905, USA.
¹⁴ Department of Genomics, Life and Brain Center, University of Bonn, Sigmund-Freud-Straße 25, 53127 Bonn, Germany.
¹⁵ Institute of Human Genetics, University of Bonn, Sigmund-Freud-Straße 25, 53127 Bonn, Germany; Department of Genomics, Life and Brain Center, University of Bonn, Sigmund-Freud-Straße 25, 53127 Bonn, Germany; Institute of Medical Biometry, Informatics, and Epidemiology, University of Bonn, Sigmund-Freud-Straße 25, 53127 Bonn, Germany.

Abstract

Previous research suggests a genetic overlap between nonsyndromic cleft lip with or without cleft palate (NSCL/P) and cancer. The aim of the present study was to identify common genetic risk loci for NSCL/P and cancer entities that have been reported to co-occur with orofacial clefting. This was achieved through the investigation of large genome-wide association study datasets. Investigations of 12 NSCL/P single nucleotide polymorphisms (SNPs) in 32 cancer datasets, and 204 cancer SNPs in two NSCL/P datasets, were performed. The SNPs rs13041247 (20q12) and rs6457327 (6p21.33) showed suggestive evidence for an association with both NSCL/P and a specific cancer entity. These loci harbor genes of biological relevance to oncogenesis (MAFB and OCT4, respectively). This study is the first to characterize possible pleiotropic risk loci for NSCL/P and cancer in a systematic manner. The data represent a starting point for future research by identifying a genetic link between NSCL/P and cancer.

Keywords: Cancer; Cleft lip; Cleft palate; Genome-wide association study; Single nucleotide polymorphism.

Abstract

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