Linking type 2 diabetes and gynecological cancer: an introductory overview

Abstract

Type 2 diabetes (T2D) is a chronic disease with a growing prevalence and a leading cause of death in many countries. Several epidemiological studies observed an association between T2D and increased risk of many types of cancer, such as gynecologic neoplasms (endometrial, cervical, ovarian and vulvar cancer). Insulin resistance, chronic inflammation and high free ovarian steroid hormones are considered the possible mechanisms behind this complex relationship. A higher risk of endometrial cancer was observed in T2D, even though this association largely attenuated after adjusting for obesity. A clear relationship between the incidence of cervical cancer (CC) and T2D has still not be determined; however T2D might have an impact on prognosis in patients with CC. To date, studies on the association between T2D and ovarian cancer (OC) are limited. The effect of pre-existing diabetes on cancer-specific mortality has been evaluated in several studies, with less clear results. Other epidemiological and experimental studies focused on the potential role of diabetes medications, mainly metformin, in cancer development in women. The correct understanding of the link between T2D and gynecologic cancer risk and mortality is currently imperative to possibly modify screening and diagnostic-therapeutic protocols in the future.

Transcriptional Profiling and Biological Pathway(s) Analysis of Type 2 Diabetes Mellitus in a Pakistani Population

“…The IPA core analysis of significant canonical pathways in T2DM subjects has also highlighted certain interconnected signaling pathways including P53 Signaling and Type 2 Diabetes Insulin Signaling in tandem with clear manifestations of Apoptosis Signaling , Molecular Mechanism of Cancer , Chronic Myeloid Leukemia , and Cell Cycle G1/S Checkpoint Regulation. TP53 is a central molecule that connects many of these pathways ( Figure 2 ),s consistent with previous studies [ 94 ], and has been associated with increased cancer risks among persons with T2DM [ 95 , 96 , 97 , 98 , 99 , 100 ].…”

MorbiNet: multimorbidity networks in adult general population. Analysis of type 2 diabetes mellitus comorbidity

“…T2DM is a known risk factor associated with pancreatic cancer 40 . A higher risk of endometrial cancer has also been observed in patients with T2DM 41 . Insulin resistance, chronic inflammation, and elevated free steroid hormones have been suggested as www.nature.com/scientificreports www.nature.com/scientificreports/ possible mechanisms involved.…”

A systematic review and meta-analysis on the effects of metformin on survival outcomes and risk in women with cervical cancer

“…Recent research shows that metformin also has an anticancer effect, functioning primarily through activation of AMP-activated protein kinase (AMPK) and regulating the activity of the AMPK/mTOR signaling pathway [17,18]. In addition, metformin can be anti-proliferative by reducing tumor vasculature through reduction in VEGF levels; increasing progesterone receptor, which increases the response to hormonal therapy; activating the AKT signaling pathway, inhibiting the IGF1R signaling pathway and reducing MRP2 expression [19][20][21].…”