Biomedical Sciences ETDs

Publication Date

7-1-2015

Abstract

There are many well-documented differences between males and females regarding melanoma including incidence rates, presentation, markers of progression, and survival. A common hypothesis to explain the female survival advantage is that males are less aware of their skin, resulting in thicker lesions at diagnosis, and ultimately poorer survival. However, there are also multiple hypotheses attributing the female survival advantage to biological differences between males and females, mostly regarding sex-steroid hormones. Sex has been identified as an independent prognostic marker in multiple studies, supporting the hypothesis that melanoma progression varies between men and women. Despite these findings, stratifying by sex in melanoma studies is uncommon. Here we present four studies investigating both behavioral and biological differences as they relate to Breslow thickness and melanoma survival in analyses stratified by sex. We found that different factors contribute to Breslow thickness and survival between males and females. Our results suggest that UV exposure is associated with increased male survival independent of Breslow thickness. UV exposure is associated with decreased Breslow thickness in females, but was not significant in the survival models suggesting that the effect was encompassed by Breslow thickness in the survival model. Furthermore, skin awareness was associated with increased survival and decreased Breslow thickness in females, but not in males. We also identified multiple SNPs in DNA repair and immune response genes that were associated with Breslow thickness, and interacted with UV exposures to modify Breslow thickness. Importantly, there was only one SNP that overlapped in the male and female analyses, and the analysis of SNPs in the overall population was not representative of the analyses stratified by sex. Our results may help explain previous inconsistencies in the literature regarding UV exposure impact on Breslow thickness and survival. Furthermore, these studies provide a good foundation for further investigating the role of UV exposures in the female survival advantage. Finally, we have demonstrated the importance of analyses stratified by sex in the study of melanoma.

Keywords

Melanoma, Breslow thickness, Sex, Skin awareness, UV exposure, SNPs, Molecular epidmiology, Immune response, DNA repair

Document Type

Dissertation

Language

English

Degree Name

Biomedical Sciences

Level of Degree

Doctoral

Department Name

Biomedical Sciences Graduate Program

First Advisor

Berwick, Marianne

First Committee Member (Chair)

Hudson, Laurie

Second Committee Member

Hartley, Rebecca

Third Committee Member

Tomkinson, Alan

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