INSR gene polymorphisms correlate with sensitivity to platinum-based chemotherapy and prognosis in patients with epithelial ovarian cancer

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Abstract

This study aimed to investigate the correlation between INSR gene polymorphisms on platinum-based chemotherapy sensitivity and prognosis in epithelial ovarian cancer (EOC). A total of 339 EOC patients receiving postoperative chemotherapy were recruited for the study. Tag single-nucleotide polymorphism of INSR gene was screened from HapMap combined with available literature. Frequency distribution of genotypes and alleles in INSR gene was sequenced by ABI3100-Avant. Compared with CC+GC genotype, INSR rs2252673 GG genotype and rs3745546 CC genotype showed less platinum-based chemotherapy sensitivity in EOC patients (odds ratio (OR) = 0.269, 95% confidence interval (CI) = 0.159 ˜ 0.456; OR = 0.445, 95% CI = 0.214 ˜ 0.926, respectively), as well as serous EOC patients (OR = 0.083, 95% CI = 0.024 ˜ 0.278; OR = 0.235, 95%CI = 0.053 ˜ 1.041, respectively). The clinical characteristics including age, clinical stage, histological grade and residual lesion size were significantly related with chemosensitivity to platinum drugs and mortality in EOC patients. According to Kaplan-Meier curve, compared with CC+GC genotype, rs2252673 GG genotype showed significantly decreased survival rate in EOC patients (P<0.05). Cox regression model indicated that rs2252673, age and clinical stage were independent risk factors for the prognosis in EOC (all P<0.05). These findings indicate that INSR rs2252673 and rs3745546 polymorphisms were associated with sensitivity to platinum-based chemotherapy in EOC patients and rs2252673 polymorphism may be an independent risk factor for EOC prognosis.

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