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Cervical cancer-associated promoter polymorphism affects akna expression levels

Genes & Immunity volume 16, pages 43–53 (2015)Cite this article

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Abstract

Cervical cancer (CC) is responsible for >260 000 deaths worldwide each year. Efforts are being focused on identifying genetic susceptibility factors, especially in genes related to the immune response. Akna has been proposed to be one of them, but data regarding its functional role in the disease is scarce. Supporting the notion of akna as a CC susceptibility gene, we found two polymorphisms associated with squamous intraepithelial lesion (SIL) and CC; moreover, we identified an association between high akna expression levels and CC and SIL, but its direction differs in each disease stage. To show the potential existence of a cis-acting polymorphism, we assessed akna allelic expression imbalance for the alleles of the −1372C>A polymorphism. We found that, regardless of the study group, the number of transcripts derived from the A allele was significantly higher than those from the C allele. Our results support the hypothesis that akna is a CC susceptibility genetic factor and suggest that akna transcriptional regulation has a role in the disease. We anticipate our study to be a starting point for in vitro evaluation of akna transcriptional regulation and for the identification of transcription factors and cis-elements regulating AKNA function that are involved in carcinogenesis.

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Acknowledgements

We thank all the patients for their participation in the study and MD Guillermina López-Estrada, Karina Delgado-Romero and David Cantú for the gynecological sampling and patient care that constitute the biological sample bank used. This work was supported by the Instituto Nacional de Salud Pública de México (INSP) and grants from CONACYT—FONSEC SSA/IMSS/ISSSTE-2011-01-161710, Mexico. GAM-N was recipient of a PhD fellowship from CONACYT. This study was also supported by the Consejo Nacional de Ciencia y Tecnología (CONACyT) and the Fondo Sectorial de Investigación en Salud y Seguridad Social, México. The supporting agency had no role in the study design; in the collection, analysis and interpretation of the data; in the preparation of the report; or in the decision to submit the article for publication. This work was submitted in partial fulfillment of the requirements for the PhD degree of GAM-N from the Doctoral Program in Health Sciences of the School of Public Health of Mexico.

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Author notes

  1. V Madrid-Marina and A I Burguete-García: These authors contributed equally to this work.

Authors and Affiliations

  1. Área de Infecciones Crónicas y Cáncer, Centro de Investigación sobre Enfermedades Infecciosas, Instituto Nacional de Salud Pública, Cuernavaca, Mexico

    G A Martínez-Nava, K Torres-Poveda, A Lagunas-Martínez, M Bahena-Román, M A Zurita-Díaz, E Ortíz-Flores, V Madrid-Marina & A I Burguete-García

  2. Unidad de Investigación Biomédica en Cáncer, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México and Instituto Nacional de Cancerología, Secretaría de Salud, Distrito Federal, Mexico

    A García-Carrancá

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  1. G A Martínez-Nava
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Martínez-Nava, G., Torres-Poveda, K., Lagunas-Martínez, A. et al. Cervical cancer-associated promoter polymorphism affects akna expression levels. Genes Immun 16, 43–53 (2015). https://doi.org/10.1038/gene.2014.60

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