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
Affiliations
Eva Dunkhase
Institute of Human Genetics, University of Bonn, Sigmund-Freud-Straße 25, 53127 Bonn, Germany
Kerstin U. Ludwig
Institute of Human Genetics, University of Bonn, Sigmund-Freud-Straße 25, 53127 Bonn, Germany
Michael Knapp
Institute of Medical Biometry, Informatics, and Epidemiology, University of Bonn, Sigmund-Freud-Straße 25, 53127 Bonn, Germany
Christine F. Skibola
Department of Epidemiology, University of Alabama at Birmingham, 1665 University Boulevard, Birmingham, AL 35294, USA
Jane C. Figueiredo
Department of Preventive Medicine, Keck School of Medicine, University of Southern California, 1975 Zonal Ave, Los Angeles, CA 90033, USA
Fay Julie Hosking
Division of Genetics and Epidemiology, The Institute of Cancer Research, 15 Cotswold Road, Sutton SM2 5NG, Surrey, UK
Eva Ellinghaus
Institute of Clinical Molecular Biology, Christian-Albrechts-University Kiel, Schittenhelmstr. 12, 24105 Kiel, Germany
Maria Teresa Landi
National Cancer Institute, NIH, DHHS, 9609 Medical Center Dr, Rockville, MD 20850, USA
Hongxia Ma
Department of Epidemiology, School of Public Health, Nanjing Medical University, 140 Hanzhong Rd, Gulou, Nanjing 210029, Jiangsu, China
Hidewaki Nakagawa
Laboratory for Genome Sequencing Analysis, RIKEN Center for Integrative Medical Sciences, 1-7-22 Suehiro-cho, Tsurumi-ku,Yokohama, Kanagawa 230-0045, Japan
Jong-Won Kim
Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, (06351) 81 Irwon-Ro Gangnam-gu. Seoul, Republic of Korea
Jiali Han
Department of Epidemiology, Richard M. Fairbanks School of Public Health, Melvin & Bren Simon Cancer Center, Indiana University, 535 Barnhill Dr, Indianapolis, IN 46202, USA
Ping Yang
Mayo Clinic, 200 First St. SW Rochester, MN 55905, USA
Anne C. Böhmer
Department of Genomics, Life and Brain Center, University of Bonn, Sigmund-Freud-Straße 25, 53127 Bonn, Germany
Manuel Mattheisen
Institute of Human Genetics, University of Bonn, Sigmund-Freud-Straße 25, 53127 Bonn, Germany
Markus M. Nöthen
Institute of Human Genetics, University of Bonn, Sigmund-Freud-Straße 25, 53127 Bonn, Germany
Elisabeth Mangold
Institute of Human Genetics, University of Bonn, Sigmund-Freud-Straße 25, 53127 Bonn, Germany
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.
