The Relevance of Gender in Tumor-Influencing Epigenetic Traits

Abstract

Tumorigenesis as well as the molecular orchestration of cancer progression are very complex mechanisms that comprise numerous elements of influence and regulation. Today, many of the major concepts are well described and a basic understanding of a tumor's fine-tuning is given. Throughout the last decade epigenetics has been featured in cancer research and it is now clear that the underlying mechanisms, especially DNA and histone modifications, are important regulators of carcinogenesis and tumor progression. Another key regulator, which is well known but has been neglected in scientific approaches as well as molecular diagnostics and, consequently, treatment conceptualization for a long time, is the subtle influence patient gender has on molecular processes. Naturally, this is greatly based on hormonal differences, but from an epigenetic point of view, the diverse susceptibility to stress and environmental influences is of prime interest. In this review we present the current view on which and how epigenetic modifications, emphasizing DNA methylation, regulate various tumor diseases. It is our aim to elucidate gender and epigenetics and their interconnectedness, which will contribute to understanding of the prospect molecular orchestration of cancer in individual tumors.

Hormones and Sex-Specific Medicine in Human Physiopathology

“…A high percentage (85%) of more than 11,000 CpG sites display increased methylation in men than in women according to a study carried out in children at different points of their lives until adolescence [145]. Further studies have substantiated the data above, showing a diversity in methylated genes, as well as in methylated CpG sites, in men and women [146]. This diversity is reported not only in discrete regions of the inactive and active X chromosome, but also in autosomal CpG sites [147].…”

Promoter Methylation of Selected Genes in Non-Small-Cell Lung Cancer Patients and Cell Lines

“…The genes CDH1, CDKN2Ap16, RASSF1A, TERT , and WT1 were selected based on their roles as biomarkers in NSCLC and their putative gender sensitivity based on the current literature and our own research findings (reviewed in [ 64 ]). Among the selected markers, RASSF1A [ 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 ] and, to a lesser extent, CDKN2Ap16 [ 73 , 74 , 75 , 76 , 77 ] are already accepted as methylation markers.…”