title: The Amerindian mtDNA haplogroup B2 enhances the risk of HPV for cervical cancer: de-regulation of mitochondrial genes may be involved.
abstract: Although human papillomavirus (HPV) infection is the main causal factor for cervical cancer (CC), there are data suggesting that genetic factors could modulate the risk for CC. Sibling studies suggest that maternally inherited factors could be involved in CC. To assess whether mitochondrial DNA (mtDNA) polymorphisms are associated to CC, HPV infection and HPV types, a case-control study was performed in the Mexican population. Polymorphism of mtDNA D-loop was investigated in 187 CC patients and 270 healthy controls. HPV was detected and typed in cervical scrapes. The expression of 29 mitochondrial genes was analyzed in a subset of 45 tumor biopsies using the expression microarray ST1.0. The Amerindian haplogroup B2 increased the risk for CC (odds ratio (OR)=1.6; 95% confidence interval (CI): 1.05-2.58) and enhanced 36% (OR=208; 95% CI: 25.2-1735.5) the risk conferred by the HPV alone (OR=152.9; 95% CI: 65.4-357.5). In cases, the distribution of HPV types was similar in all haplogroups but one (D1), in which is remarkable the absence of HPV18, a very low frequency of HPV16 and high frequencies of HPV45, HPV31 and other HPV types. Two mtDNA genes (mitochondrial aspartic acid tRNA (MT-TD), mitochondrial lysine tRNA (MT-TK)) could be involved in the increased risk conferred by the haplogroup B2, as they were upregulated exclusively in B2 tumors (P<0.01, t-test). Although the association of mtDNA with CC and HPV infection is clear, other studies with higher sample size will be needed to elucidate the role of mtDNA in cervical carcinogenesis.
authors.affiliation: Unidad de Medicina Genómica, Hospital General de México, Universidad Nacional Autónoma de México, Mexico City, Mexico.
authors.forename: Mariano
authors.initials: M
authors.lastname: Guardado-Estrada
authors.forename: Ingrid
authors.initials: I
authors.lastname: Medina-Martínez
authors.forename: Eligia
authors.initials: E
authors.lastname: Juárez-Torres
authors.forename: Edgar
authors.initials: E
authors.lastname: Roman-Bassaure
authors.forename: Luis
authors.initials: L
authors.lastname: Macías
authors.forename: Ana
authors.initials: A
authors.lastname: Alfaro
authors.forename: Avissai
authors.initials: A
authors.lastname: Alcántara-Vázquez
authors.forename: Patricia
authors.initials: P
authors.lastname: Alonso
authors.forename: Guillermo
authors.initials: G
authors.lastname: Gomez
authors.forename: Fernando
authors.initials: F
authors.lastname: Cruz-Talonia
authors.forename: Luis
authors.initials: L
authors.lastname: Serna
authors.forename: Sergio
authors.initials: S
authors.lastname: Muñoz-Cortez
authors.forename: Manuel
authors.initials: M
authors.lastname: Borges-Ibañez
authors.forename: Ana
authors.initials: A
authors.lastname: Espinosa
authors.forename: Susana
authors.initials: S
authors.lastname: Kofman
authors.forename: Jaime
authors.initials: J
authors.lastname: Berumen
mesh_terms: D000328:Adult; D000483:Alleles; D016022:Case-Control Studies; D004272:DNA, Mitochondrial / Q000235:genetics*; D004279:DNA, Viral / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005787:Gene Frequency; D050259:Genes, Mitochondrial; D006239:Haplotypes; D052162:Human papillomavirus 16 / Q000235:genetics / Q000472:pathogenicity; D052161:Human papillomavirus 18 / Q000235:genetics / Q000472:pathogenicity; D058952:Human papillomavirus 31 / Q000235:genetics / Q000472:pathogenicity; D006801:Humans; D007198:Indians, North American / Q000235:genetics*; D008875:Middle Aged; D008928:Mitochondria / Q000235:genetics; D012307:Risk Factors; D002583:Uterine Cervical Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000821:virology; D055815:Young Adult
chemical_list: D004272:DNA, Mitochondrial; D004279:DNA, Viral