Endogenous DNA damage and testicular germ cell tumors

Abstract

Testicular germ cell tumors are comprised of two histologic groups, seminomas and non-seminomas. We postulated that the possible divergent pathogeneses of these histologies may be partially explained by variable levels of net endogenous DNA damage. To test our hypothesis, we conducted a case-case analysis of 51 seminoma and 61 non-seminoma patients using data and specimens from the Familial Testicular Cancer study and the U.S. Radiologic Technologists cohort. A lymphoblastoid cell line was cultured for each patient and the alkaline comet assay was used to determine four parameters: tail DNA, tail length, comet distributed moment (CDM) and Olive tail moment (OTM). Odds ratios (OR) and 95% confidence intervals (95% CI) were estimated using logistic regression. Values for tail length, tail DNA, CDM and OTM were modelled as categorical variables using the 50th and 75th percentiles of the seminoma group. Tail DNA was significantly associated with non-seminoma compared with seminoma (OR(50th percentile) = 3.31, 95% CI: 1.00, 10.98; OR(75th percentile) = 3.71, 95% CI: 1.04, 13.20; p for trend = 0.039). OTM exhibited similar, albeit statistically non-significant, risk estimates (OR(50th percentile) = 2.27, 95% CI: 0.75, 6.87; OR(75th percentile) = 2.40, 95% CI: 0.75, 7.71; p for trend = 0.12) whereas tail length and CDM showed no association. In conclusion, the results for tail DNA and OTM indicate that net endogenous levels are higher in patients who develop non-seminoma compared with seminoma. This may partly explain the more aggressive biology and younger age-of-onset of this histologic subgroup compared with the relatively less aggressive, later-onset seminoma.

FIGURE. Boxplots of comet parameters by testicular germ cell tumor histology

(a) tail DNA; (b) Olive tail moment. Each boxplot represents the geometric means of the respective comet parameter of 100 cells for each individual within the nonseminoma or seminoma group. The boxplots display the median (thick line), interquartile range (lower and upper box borders), the 5th and 95th percentiles (error bars), and extreme individual values (●).

FIGURE. Boxplots of comet parameters by testicular germ cell tumor histology

(a) tail DNA; (b) Olive tail moment. Each boxplot represents the geometric means of the respective comet parameter of 100 cells for each individual within the nonseminoma or seminoma group. The boxplots display the median (thick line), interquartile range (lower and upper box borders), the 5th and 95th percentiles (error bars), and extreme individual values (●).