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Significant association of the EXO1 rs851797 polymorphism with clinical outcome of ovarian cancer.

ABSTRACT: BACKGROUND:Exonuclease 1 (EXO1), one of DNA mismatch repair pathway genes, functions in maintaining genomic stability and affects tumor progression. We hypothesized that genetic variations in EXO1 may predict clinical outcomes in epithelial ovarian cancer (EOC). METHODS:In this cohort study with 1,030 consecutive EOC patients, we genotyped four potentially functional polymorphisms in EXO1 by the Taqman assay and evaluated their associations with patients' survival. RESULTS:Using multivariate Cox proportional hazards regression models, we found that rs851797AG/GG genotypes were significantly associated with recurrence and cancer death (HR =1.30 and 1.38, 95% CI =1.11-1.52 and 1.02-1.88, respectively). Kaplan-Meier survival estimates showed that patients who carried rs851797AG/GG genotypes had poorer progression-free survival and poorer overall survival, compared with rs851797AA genotype carriers (log-rank test, P=0.002 and 0.025, respectively). Moreover, patients with older age at menophania, advanced stage tumor, or being received incomplete cytoreduction were more likely to be recurrent and dead. CONCLUSION:EXO1 rs851797 polymorphism can predict the clinical outcomes in EOC patients. In addition, age at menophania, FIGO stage, and complete cytoreduction might be independently prognostic factors of ovarian cancer. Large studies with functional experiments are warranted to validate these findings.

SUBMITTER: Shi T

PROVIDER: S-EPMC5633322 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Significant association of the <i>EXO1</i> rs851797 polymorphism with clinical outcome of ovarian cancer.

Shi Tingyan T Jiang Rong R Wang Pan P Xu Yuan Y Yin Sheng S Cheng Xi X Zang Rongyu R

OncoTargets and therapy 20171003

<h4>Background</h4>Exonuclease 1 (<i>EXO1</i>), one of DNA mismatch repair pathway genes, functions in maintaining genomic stability and affects tumor progression. We hypothesized that genetic variations in <i>EXO1</i> may predict clinical outcomes in epithelial ovarian cancer (EOC).<h4>Methods</h4>In this cohort study with 1,030 consecutive EOC patients, we genotyped four potentially functional polymorphisms in <i>EXO1</i> by the Taqman assay and evaluated their associations with patients' surv ...[more]

PMID: 29042795

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Project description:There is evidence that some ovarian tumours evoke an immune response, which can be assessed by tumour infiltrating lymphocytes (TILs). To facilitate adoption of TILs as a clinical biomarker, a standardised method for their H&E visual evaluation has been validated in breast cancer.We sought to investigate the prognostic significance of TILs in a study of 953 invasive epithelial ovarian cancer tumour samples, both primary and metastatic, from 707 patients from the prospective population-based SEARCH study. TILs were analysed using a standardised method based on H&E staining producing a percentage score for stromal and intratumoral compartments. We used Cox regression to estimate hazard ratios of the association between TILs and survival.The extent of stromal and intra-tumoral TILs were correlated in the primary tumours (n = 679, Spearman's rank correlation = 0.60, P < 0.001) with a similar correlation in secondary tumours (n = 224, Spearman's rank correlation = 0.62, P < 0.001). There was a weak correlation between stromal TIL levels in primary and secondary tumour samples (Spearman's rank correlation = 0.29, P < 0.001) and intra-tumoral TIL levels in primary and secondary tumour samples (Spearman's rank correlation = 0.19, P = 0.0094). The extent of stromal TILs differed between histotypes (Pearson chi2 (12d.f.) 54.1, P < 0.0001) with higher levels of stromal infiltration in the high-grade serous and endometriod cases. A significant association was observed for higher intratumoral TIL levels and a favourable prognosis (HR 0.74 95% CI 0.55-1.00 p = 0.047).This study is the largest collection of epithelial ovarian tumour samples evaluated for TILs. We have shown that stromal and intratumoral TIL levels are correlated and that their levels correlate with clinical variables such as tumour histological subtype. We have also shown that increased levels of both intratumoral and stromal TILs are associated with a better prognosis; however, this is only statistically significant for intratumoral TILs. This study suggests that a clinically useful immune prognostic indicator in epithelial ovarian cancer could be developed using this technique.

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Significant association of the EXO1 rs851797 polymorphism with clinical outcome of ovarian cancer.

Publications

Significant association of the <i>EXO1</i> rs851797 polymorphism with clinical outcome of ovarian cancer.

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