Gender and ploidy in cancer survival

Abstract

Background: Females carry a better prognosis than men for many cancer types. We hypothesized that chromosomal changes, in particular numerical alterations of the sex chromosomes or the presence of near-triploidy may contribute to these gender differences.

Methods: To characterize the influence of gender a literature search was performed for survival data of 27 tumor types. All entities were categorized by the strength of evidence for differences in survival between females and males. To test our hypothesis the Mitelman database of chromosomal alterations was evaluated for the major tumor types occurring in both women and men. Numerical gonosome alterations were documented and mean chromosome numbers were converted into histograms to provide insight into the ploidy level of 37 cancer types.

Results: In general, a survival advantage of women could be shown for most, but not all cancer types. In addition, 36.859 karyograms were analyzed. Numerical gonosome alterations were more frequent in males than females indicating a potential link with gender differences in survival. Neartriploidy was a common phenomenon in many cancer types suggesting that it represents a metastable condition of the cancer genome. It was not related to gender differences in survival. However, the extent of triploidy and aneuploidy was associated with poor prognosis in carcinomas. There was no single case in the Mitelman database with normal chromosome number (n = 46) that did not carry at least one structural or numerical aberration.

Conclusions: Our study highlights the importance of chromosomal changes in tumor formation and progression. In addition, it suggests potential associations with gender specific differences in survival.

Fig. 1

Examples for ploidy analysis of tumor entities. Histograms showing the frequency of chromosome numbers in tumor entities for men and women

Fig. 2

Correlation between the extent of (aneu)ploidy states and mean 5-year survival rate in different carcinomas. Each point correspond to one carcinoma entity as indicated. The survival rates were correlated with the percentage of cases within each entity showing hyperdiploid (No.chr.>47), predominant hypertriploid (No.chr .> 57), predominant triploid (No.chr. 57–83) and aneuploid (No.chr. ≠ 45–47, ≠ 90–92) chromosome numbers. The correlation coefficients (r) indicate significant correlations between these (aneu)ploidy states and the 5-year survival rates

Fig. 3

Analysis of percentage of cases with XX or XY numerical alterations in the different tumor entities (blue colour: percentage of cases in men with XY numerical alterations; red colour: percentage of cases in women with XX numerical alterations)