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Systematic Review of Candidate Single-nucleotide Polymorphisms as Biomarkers for Responsiveness to Neoadjuvant
Elizabeth D Maring1, Patrick S Tawadros2, Clifford J Steer3
1Department of Genetics, Cell Biology and Development, College of Biological Sciences, University of Minnesota, Minneapolis, MN, U.S.A.
Background/Aim:
Treatment of rectal cancer has improved significantly with the addition of neoadjuvant chemoradiation. Certain patients have experienced a complete pathological response to chemoradiation, as observed in surgically resected tissue samples, thus calling into question the necessity of radical surgery in this population of patients. Pharmacogenetic studies now implicate the role that genetic biomarkers, such as single nucleotide polymorphisms, play in an individual's response to chemoradiation. The aim of this review was to provide a comprehensive evaluation of a group of candidate single nucleotide polymorphisms associated with chemoradiotherapy response and an assessment of techniques that can be used to easily identify the presence of these single nucleotide polymorphisms in patient samples.
Materials And Methods:
Relevant primary research articles were identified in the Medline Database from January 1, 2006 to May 31, 2012. We included nine relevant articles addressing the correlation between six candidate single nucleotide polymorphisms and one candidate variable number tandem repeat in six genes, namely thymidylate synthase, epidermal growth factor, epidermal growth factor receptor, superoxide dismutase 2, interleukin-13, and cyclin D1, with tumor down-staging and patient survival after neoadjuvant chemotherapy or chemoradiotherapy.
Results:
Specific alleles of each of the candidate single nucleotide polymorphisms were significantly associated with either a major response in tumor down-staging or a minor to non-existent response following neoadjuvant chemotherapy, individually or in combination with other single nucleotide polymorphisms. However, studies present conflicting results regarding the effect of certain candidate single nucleotide polymorphisms on tumor down-staging.
Conclusion:
Through further research into candidate single nucleotide polymorphisms and potential identification of other polymorphisms, clinicians may be able to create individualized treatment plans in accordance with the genotype of individual patients with rectal cancer, in order to reduce morbidity and mortality.
