title: Integrative genomic analysis identifies ancestry-related expression quantitative trait loci on DNA polymerase β and supports the association of genetic ancestry with survival disparities in head and neck squamous cell carcinoma.
abstract: African Americans with head and neck squamous cell carcinoma (HNSCC) have a lower survival rate than whites. This study investigated the functional importance of ancestry-informative single-nucleotide polymorphisms (SNPs) in HNSCC and also examined the effect of functionally important genetic elements on racial disparities in HNSCC survival.
  
  
  
  Ancestry-informative SNPs, RNA sequencing, methylation, and copy number variation data for 316 oral cavity and laryngeal cancer patients were analyzed across 178 DNA repair genes. The results of expression quantitative trait locus (eQTL) analyses were also replicated with a Gene Expression Omnibus (GEO) data set. The effects of eQTLs on overall survival (OS) and disease-free survival (DFS) were evaluated.
  
  
  
  Five ancestry-related SNPs were identified as cis-eQTLs in the DNA polymerase β (POLB) gene (false discovery rate [FDR] < 0.01). The homozygous/heterozygous genotypes containing the African allele showed higher POLB expression than the homozygous white allele genotype (P < .001). A replication study using a GEO data set validated all 5 eQTLs and also showed a statistically significant difference in POLB expression based on genetic ancestry (P = .002). An association was observed between these eQTLs and OS (P < .037; FDR < 0.0363) as well as DFS (P = .018 to .0629; FDR < 0.079) for oral cavity and laryngeal cancer patients treated with platinum-based chemotherapy and/or radiotherapy. Genotypes containing the African allele were associated with poor OS/DFS in comparison with homozygous genotypes harboring the white allele.
  
  
  
  Analyses show that ancestry-related alleles could act as eQTLs in HNSCC and support the association of ancestry-related genetic factors with survival disparities in patients diagnosed with oral cavity and laryngeal cancer. Cancer 2017;123:849-60. © 2016 American Cancer Society.
authors.affiliation: Cancer Prevention and Control Program, Fox Chase Cancer Center-Temple Health, Philadelphia, Pennsylvania.|Department of Biology, Temple University, Philadelphia, Pennsylvania.|Center for Computational Genetics and Genomics, Temple University, Philadelphia, Pennsylvania.|Institute for Genomics and Evolutionary Medicine, Temple University, Philadelphia, Pennsylvania.|African-Caribbean Cancer Consortium, Philadelphia, Pennsylvania.
authors.forename: Meganathan P
authors.initials: MP
authors.lastname: Ramakodi
authors.affiliation: Biostatistics and Bioinformatics Facility, Fox Chase Cancer Center-Temple Health, Philadelphia, Pennsylvania.|Department of Epidemiology and Biostatistics, College of Public Health, Temple University, Philadelphia, Pennsylvania.|Center for High-Dimensional Statistics, Big Data Institute, Temple University, Philadelphia, Pennsylvania.
authors.forename: Karthik
authors.initials: K
authors.lastname: Devarajan
authors.affiliation: Cancer Prevention and Control Program, Fox Chase Cancer Center-Temple Health, Philadelphia, Pennsylvania.|African-Caribbean Cancer Consortium, Philadelphia, Pennsylvania.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Blackman
authors.affiliation: Cancer Prevention and Control Program, Fox Chase Cancer Center-Temple Health, Philadelphia, Pennsylvania.|African-Caribbean Cancer Consortium, Philadelphia, Pennsylvania.
authors.forename: Denise
authors.initials: D
authors.lastname: Gibbs
authors.affiliation: African-Caribbean Cancer Consortium, Philadelphia, Pennsylvania.|National Institute for Health and Medical Research (INSERM), Unit 1085;, Institute for Research in Health, Environment, and Work (IRSET), Pointe-à-Pitre, Guadeloupe, French West Indies.
authors.forename: Danièle
authors.initials: D
authors.lastname: Luce
authors.affiliation: African-Caribbean Cancer Consortium, Philadelphia, Pennsylvania.|General Cancer Registry of Guadeloupe, University Hospital of Pointe-à-Pitre, Pointe-a-Pitre, Guadeloupe, French West Indies.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Deloumeaux
authors.affiliation: Department of Oto-Rhino-Laryngology and Head and Neck Surgery, University Hospital of Pointe à Pitre, Pointe-a-Pitre, Guadeloupe, French West Indies.
authors.forename: Suzy
authors.initials: S
authors.lastname: Duflo
authors.affiliation: Head and Neck Surgery, Fox Chase Cancer Center-Temple Health, Philadelphia, Pennsylvania.|Department of Otolaryngology-Head and Neck Surgery, Lewis Katz School of Medicine, Temple University School of Medicine, Philadelphia, Pennsylvania.
authors.forename: Jeffrey C
authors.initials: JC
authors.lastname: Liu
authors.affiliation: Department of Hematology/Oncology, Fox Chase Cancer Center-Temple Health, Philadelphia, Pennsylvania.
authors.forename: Ranee
authors.initials: R
authors.lastname: Mehra
authors.affiliation: Department of Biology, Temple University, Philadelphia, Pennsylvania.|Center for Computational Genetics and Genomics, Temple University, Philadelphia, Pennsylvania.|Institute for Genomics and Evolutionary Medicine, Temple University, Philadelphia, Pennsylvania.|African-Caribbean Cancer Consortium, Philadelphia, Pennsylvania.
authors.forename: Rob J
authors.initials: RJ
authors.lastname: Kulathinal
authors.affiliation: Cancer Prevention and Control Program, Fox Chase Cancer Center-Temple Health, Philadelphia, Pennsylvania.|African-Caribbean Cancer Consortium, Philadelphia, Pennsylvania.|Department of Epidemiology and Biostatistics, College of Public Health, Temple University, Philadelphia, Pennsylvania.|Department of Otolaryngology-Head and Neck Surgery, Lewis Katz School of Medicine, Temple University School of Medicine, Philadelphia, Pennsylvania.
authors.forename: Camille C
authors.initials: CC
authors.lastname: Ragin
mesh_terms: D000328:Adult; D001741:Black or African American / Q000235:genetics; D000368:Aged; D000483:Alleles; D002294:Carcinoma, Squamous Cell / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D056915:DNA Copy Number Variations; D019951:DNA Polymerase beta / Q000235:genetics*; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D056726:Genetic Association Studies; D005838:Genotype; D006258:Head and Neck Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D006801:Humans; D007822:Laryngeal Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009055:Mouth / Q000473:pathology; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D040641:Quantitative Trait Loci / Q000235:genetics*; D017423:Sequence Analysis, RNA; D000077195:Squamous Cell Carcinoma of Head and Neck; D044465:White People / Q000235:genetics
chemical_list: D019951:DNA Polymerase beta
keywords: DNA polymerase β; expression quantitative trait locus (eQTL); genetic ancestry; head and neck squamous cell carcinoma; survival disparity