Genetic variations in the PI3K/AKT pathway predict platinum-based neoadjuvant chemotherapeutic sensitivity in squamous cervical cancer

Aims: Cervical cancer is one of the most frequent malignant turnouts in women. The PI3K/Akt pathway plays a role in chemoresistance to platinum-based neoadjuvant chemotherapy (NAC). The objective of this study was to evaluate the association between genetic polymorphisms in the PI3K/Akt pathway and chemotherapeutic outcomes following platinum-based NAC in Northwestern Chinese Han patients with squamous cervical cancer (SCC). Main methods: In total, 17 tagging single nucleotide polymorphisms (tSNPs) in four genes (PIK3CA, Akt1, Akt2, PTEN) were identified as being associated with chemotherapeutic response in 259 patients with stage IB2-IIB SCC. Each of these patients received more than two cycles of NAC. These tSNPs were genotyped by the Sequenom MassArray system. Key findings: The heterozygous genotype of two loci in the PIK3CA gene (rs3729679: uncorrected P = 0.022 and rs12494623: uncorrected P = 0.018) was associated with an increased risk of chemoresistance in SCC patients. The stratified analysis also showed that these same SNP polymorphisms were associated with a poor response to NAC in the cisplatin-based subgroup. Furthermore, NAC non-responders had a higher frequency of the rs10416620 and rs62107593 G alleles in the Akt2 gene (rs10416620 and rs62107593: uncorrected P = 0.037). The rs34716810 A allele was associated with a poor response to chemotherapy (uncorrected P = 0.037). Moreover, rs2498786 (uncorrected P = 0.036) and the GGCC haplotype of polymorphisms in Akt1 showed a high risk for non-response to NAC (uncorrected P = 0.018). Significance: The findings from this study demonstrate that genetic polymorphisms in the PI3K/Akt pathway are associated with sensitivity to platinum-based chemotherapy in SCC patients. (C) 2015 Published by Elsevier Inc.