Login to Access Video or Poster Abstract: MP39-17
Sources of Funding: none

Introduction

Peripheral blood mitochondrial DNA (mtDNA) is suggested as a risk factor for several types of cancer. Previous studies have assessed the association between mtDNA and renal cell carcinoma (RCC), however, contradictory results were obtained. The aim of the present study was to assess the role of peripheral blood mtDNA in prediction and early detection of renal cell carcinoma in a cohort of Egyptian patients.

Methods

The study enrolled 57 patients with early localized RCC (TNM stage I and II), confirmed by histopathological examination. They were consecutively recruited between August 2012 and March 2015 after excluding patients with advanced RCC (TNM stage III and IV) (to omit the effect of disease progression on mtDNA content), patients with other malignancies, family history of kidney cancer, recurrent RCC, and patients who received neoadjuvant therapy. Sixty healthy individuals with matching age and sex were included as control. The Ethics Committee approved this study and all subjects gave informed consent._x000D_ Relative mtDNA copy number was measured using quantitative real-time PCR assay. Mitochondrial DNA (mtDNA) copy number was determined relative to the nuclear gene (HBB gene) using the formula^-2δδCt._x000D_

Results

Fifty seven patients (36 males, 21 females) diagnosed with early localized RCC were included: 50 clear RCC,5 papillary RCC and 2 chromophobe RCC cases. The mean age was 60.14 ± 6.83 years. Median mtDNA copy number was significantly higher in RCC cases than controls (166 vs 91, P<0.001). The role of mtDNA copy number as a risk factor for RCC was evaluated using unconditional logistic regression analysis. The median mtDNA content of the control group (91) was used as a cutoff value to analyze mtDNA copy number. It was found that patients with mtDNA content higher than 91 had a significant increase in RCC risk of 18 fold than those with lower levels with OR (odds ratio) of 18.0 (95% CI = 5.065-63.9) in univariate analysis and an adjusted OR of 18.9 (95% CI = 5.11-70.11) in multivariate analysis (after adjusting for age, gender, smoking status, hypertension and body mass index)._x000D_ The diagnostic value of mtDNA content in early detection of RCC was further assessed. Using receiver operating curve (ROC curve) analysis, it was found that mtDNA can detect RCC at a cutoff value of 108.5 with 86% sensitivity, 80% specificity, 80.3 % positive predictive value and 85.7% negative predictive value._x000D_

Conclusions

Increased mtDNA copy number could be used as a potential independent predictor of RCC risk. In addition, it may serve as a promising non-invasive biomarker for early detection of RCC.

Funding

none