The Sex Bias of Cancer

Costa, Ana Lúcia Siqueira; Oliveira, Mariana Lança de; Cruz, Inés Seoane; Gonçalves, Isabel; Cascalheira, José F.; Santos, Cecília R. A.

doi:10.1016/j.tem.2020.07.002

Cited by 49 publications

(34 citation statements)

References 88 publications

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“…From the current epidemiologic data, it is expected by the year 2040 there will be around 2 million new cases and 1 million deaths due to CRC ( 15 ). Even with comparable lifestyle choices, it appears that women maintain a higher level of protection than men against CRC, implicating sexual dimorphism as a key element in future research and therapeutic strategies ( 293 ).…”

Section: Gender Gap In Crcmentioning

confidence: 99%

Sexual Dimorphism in Colon Cancer

et al. 2020

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A higher incidence of colorectal cancer (CRC) is found in males compared to females. Young women (18–44 years) with CRC have a better survival outcome compared to men of the same age or compared to older women (over 50 years), indicating a global incidence of sexual dimorphism in CRC rates and survival. This suggests a protective role for the sex steroid hormone estrogen in CRC development. Key proliferative pathways in CRC tumorigenesis exhibit sexual dimorphism, which confer better survival in females through estrogen regulated genes and cell signaling. Estrogen regulates the activity of a class of Kv channels (KCNQ1:KCNE3), which control fundamental ion transport functions of the colon and epithelial mesenchymal transition through bi-directional interactions with the Wnt/β-catenin signalling pathway. Estrogen also modulates CRC proliferative responses in hypoxia via the novel membrane estrogen receptor GPER and HIF1A and VEGF signaling. Here we critically review recent clinical and molecular insights into sexual dimorphism of CRC biology modulated by the tumor microenvironment, estrogen, Wnt/β-catenin signalling, ion channels, and X-linked genes.

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Section: Gender Gap In Crcmentioning

confidence: 99%

Sexual Dimorphism in Colon Cancer

et al. 2020

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“…Asthma is more common in males from birth until puberty but becomes more prevalent and more severe in females after puberty [17]. Furthermore, other diseases where the immune system does not seem in-volved show differences between males and females: cancer, neurodevelopmental diseases, neurodegenerative, and cardiovascular diseases [8,18].…”

Section: Diseases With Altered Sex Ratiomentioning

confidence: 99%

“…Cancer development has been observed more in men than women, especially for non-reproductive cancers (with few exceptions, such as thyroid cancer and lung cancer in nonsmokers) or cancers developed in the larynx, esophagus, and bladder, which show a male preponderance of 2:1 and 4:1 respectively, generally with a poor prognosis [18][19][20].…”

Section: Diseases With Altered Sex Ratiomentioning

confidence: 99%

Gender Specific Differences in Disease Susceptibility: The Role of Epigenetics

2021

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Many complex traits or diseases, such as infectious and autoimmune diseases, cancer, xenobiotics exposure, neurodevelopmental and neurodegenerative diseases, as well as the outcome of vaccination, show a differential susceptibility between males and females. In general, the female immune system responds more efficiently to pathogens. However, this can lead to over-reactive immune responses, which may explain the higher presence of autoimmune diseases in women, but also potentially the more adverse effects of vaccination in females compared with in males. Many clinical and epidemiological studies reported, for the SARS-CoV-2 infection, a gender-biased differential response; however, the majority of reports dealt with a comparable morbidity, with males, however, showing higher COVID-19 adverse outcomes. Although gender differences in immune responses have been studied predominantly within the context of sex hormone effects, some other mechanisms have been invoked: cellular mosaicism, skewed X chromosome inactivation, genes escaping X chromosome inactivation, and miRNAs encoded on the X chromosome. The hormonal hypothesis as well as other mechanisms will be examined and discussed in the light of the most recent epigenetic findings in the field, as the concept that epigenetics is the unifying mechanism in explaining gender-specific differences is increasingly emerging.

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“…The third actor considered herein is related to the sex/gender disparity observed in many forms of cancers [25,26]. In fact, significant sex/gender differences in cancer incidence, progression, and response to therapy have been reported [26][27][28][29][30]. Importantly, differences in the clinical outcome have recently been reported for many types of tumors [30][31][32].…”

Section: Sex Differences In Cancermentioning

confidence: 99%

The Sex-Related Interplay between TME and Cancer: On the Critical Role of Estrogen, MicroRNAs and Autophagy

Matarrese

Mattia

Pagano

et al. 2021

Cancers

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The interplay between cancer cells and the tumor microenvironment (TME) has a fundamental role in tumor progression and response to therapy. The plethora of components constituting the TME, such as stroma, fibroblasts, endothelial and immune cells, as well as macromolecules, e.g., hormones and cytokines, and epigenetic factors, such as microRNAs, can modulate the survival or death of cancer cells. Actually, the TME can stimulate the genetically regulated programs that the cell puts in place under stress: apoptosis or, of interest here, autophagy. However, the implication of autophagy in tumor growth appears still undefined. Autophagy mainly represents a cyto-protective mechanism that allows cell survival but, in certain circumstances, also leads to the blocking of cell cycle progression, possibly leading to cell death. Since significant sex/gender differences in the incidence, progression and response to cancer therapy have been widely described in the literature, in this review, we analyzed the roles played by key components of the TME, e.g., estrogen and microRNAs, on autophagy regulation from a sex/gender-based perspective. We focused our attention on four paradigmatic and different forms of cancers—colon cancer, melanoma, lymphoma, and lung cancer—concluding that sex-specific differences may exert a significant impact on TME/cancer interaction and, thus, tumor growth.

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The Sex Bias of Cancer

Cited by 49 publications

References 88 publications

Sexual Dimorphism in Colon Cancer

Sexual Dimorphism in Colon Cancer

Gender Specific Differences in Disease Susceptibility: The Role of Epigenetics

The Sex-Related Interplay between TME and Cancer: On the Critical Role of Estrogen, MicroRNAs and Autophagy

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