Cancer and Tumour Suppressor p53 Encounters at the Juncture of Sex Disparity

Abstract

There are many differences in cancer manifestation between men and women. New understanding of the origin of these point to fundamental distinctions in the genetic code and its demise. Tumour suppressor protein p53 is the chief operating officer of cancer defence and critically acts to safeguard against sustained DNA damaged. P53 cannot be ignored in cancer sex disparity. In this review we discuss the greater prevalence and associated death rates for non-reproductive cancers in males. The major tumour suppressor protein p53, encoded in the TP53 gene is our chosen context. It is fitting to ask why somatic TP53 mutation incidence is estimated to be disproportionately higher among males in the population for these types of cancers compared with females? We scrutinised the literature for evidence of predisposing genetic and epigenetic alterations that may explain this sex bias. Our second approach was to explore whether redox activity, either externally imposed or inherent to males and females, may define distinct risks that could contribute to the clear cancer sex disparities.

Keywords: SNPs; cancer; epigenetics; non-coding RNAs; oxidative stress; p53; post translational modifications; sex disparity.

FIGURE 1

p53 tumour suppressor activities are not equally enforced between the sexes in non-reproductive cancers. P53 is termed the Guardian of the Genome (Lane, 1992) because of its key role in cancer prevention (top panel). P53 function may be less robust when undermined through cell intrinsic events, with emerging sex disparities (middle panel; “Altered TP53 Regulation and Its Cancer Risks for Females and Males” section). TP53 mutation is a particular risk for non-reproductive cancers in males (blue tonings), with oxidative stress an imposed danger (bottom panel; “Cancer Sex Disparity Linked to Redox Activity Through p53” section).