Diabetes mellitus and gynecologic cancer: molecular mechanisms, epidemiological, clinical and prognostic perspectives

Vrachnis, Nikolaos; Iavazzo, Christos; Iliodromiti, Zoe; Sifakis, Stavros; Alexandrou, Andreas; Siristatidis, Charalambos; Grigoriadis, C; Botsis, D.; Creatsas, George

doi:10.1007/s00404-015-3858-z

Cited by 56 publications

(48 citation statements)

References 74 publications

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“…Unilateral distribution of the missing teeth was present in 60.8% of the patients included in the review. Different parameters are correlated with ovarian cancer such as history of diabetes mellitus or endometriosis (19,20). The review of the current literature reveals strong correlation between hypodontia and ovarian cancer.…”

Section: Discussionmentioning

confidence: 99%

Hypodontia and ovarian cancer: A systematic review

Iavazzo

Papakiritsis²,

Gkegkes

2016

J Turkish German Gynecol Assoc

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Spanish were excluded from this review. The retrieved data from each of the included studies were focused on the publication type, the number of patients included in each study, the number of patients included in the control group, the incidence of hypodontia, the number of missing teeth, the type of missing teeth, the distribution of hypodontia, the presence of ovarian cancer in family medical history, and the presence of isolated genes correlated to ovarian cancer. ResultsThe performed search in PubMed and Scopus revealed a total of 43 and 39 search results, respectively, among which 4 studies (4 case series) were identified as eligible for inclusion in this review, according to the inclusion criteria (8)(9)(10)(11). No additional studies were identified by searching the references of the included studies. The selected studies for inclusion are presented in detail in Figure 1 (flow diagram). The principal characteristics of the included studies in our review (publication type, number of patients, control group, incidence of hypodontia, number of missing teeth, type of missHypodontia can be defined as the non-formation of one or more teeth during the developmental period. Mutation in several genes related to tooth formation has previously been correlated with cancer. Regarding the ovarian cancer, there are few studies that associate the presence of hypodontia with ovarian cancer. A systematic literature search was performed in PubMed and Scopus. In total, 385 patients were included in this study. Control group was present in 3 out of 4 studies (340 patients). Hypodontia was present in 56 out of 290 patients (incidence of 19.3%). Only in 2 out of 4 studies, the number of missing teeth was mentioned (47 teeth), while the majority of them were either maxillary second premolars or maxillary lateral incisors. Unilateral distribution of the missing teeth was present in 28 out of 46 patients, while bilateral distribution of the missing teeth was present in 18 out of 46 patients. The presence of ovarian cancer in the family medical history occurred in 12 out of 33 patients. Only 1 out of 4 studies examined the presence of genes with mutations in the included patients. Based on our findings, the lack of clinical studies was the principal obstacle to clarify the possible predictive value of hypodontia in the early prediction of patients with higher risk of ovarian cancer. (J Turk Ger Gynecol Assoc 2016; 17: 41-4) Keywords: Hypodontia Abstract ing teeth, distribution of hypodontia, presence of ovarian cancer in family medical history, and isolated genes) are presented in Table 1. In total, 385 patients were included in this study. Control group was present in 3 out of 4 studies (340 patients). Hypodontia was present in 56 out of 290 patients (19.3%). Only in 2 out of 4 studies, the number of missing teeth was mentioned (47 teeth), and the majority of them were either maxillary second premolars or maxillary lateral incisors. Unilateral distribution of the missing teeth was present in 28 out of 46 patients, while bilater...

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Section: Discussionmentioning

confidence: 99%

Hypodontia and ovarian cancer: A systematic review

Iavazzo

Papakiritsis²,

Gkegkes

2016

J Turkish German Gynecol Assoc

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“…A stronger association was found in studies that controlled for age, BMI, smoking, and alcohol use (RR 1.55, 95% CI 1.11–2.19) [23]. Vrachnis et al demonstrated an increased risk for ovarian cancer in premenopausal, but not post-menopausal, diabetic women [9]. Conversely, Chen et al followed a cohort of Taiwanese women (n = 319,310 with diabetes, n = 319,308 without DM) for nine years and failed to show an increased incidence of EOC (adjusted HR = 1.06, 95% CI 0.92–1.42) [24].…”

Section: Diabetes Mellitus and Epithelial Ovarian Cancermentioning

confidence: 99%

“…Among adults with DM, approximately 60% also have obesity and 80% have a BMI > 25 [8]. The link between DM and EOC incidence is debated [9]; however, DM has been clearly associated with poorer outcomes and shorter survival in EOC [4,10]. MetS is defined by the presence of three of the five following metabolic derangements in an individual: elevated waist circumference (population and country specific cutoffs), elevated triglycerides (≥150 mg/dL), reduced high-density lipoprotein cholesterol (<40 mg/dL in males, <50 mg/dL in females), hypertension (systolic ≥ 130, diastolic ≥ 85), and elevated fasting glucose (≥ 100 mg/dL) [11].…”

Section: Introductionmentioning

confidence: 99%

Metabolic risk factors and mechanisms of disease in epithelial ovarian cancer: A review

Craig

Londoño

Norian

et al. 2016

Gynecologic Oncology

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Objective Epithelial ovarian cancer continues to be the deadliest gynecologic malignancy. Patients with both diabetes mellitus and obesity have poorer outcomes, yet research correlating metabolic abnormalities, such as metabolic syndrome, to ovarian cancer risk and outcomes is lacking. This article reviews the literature regarding metabolic derangements and their relationship to epithelial ovarian cancer, with a focus on potential mechanisms behind these associations. Methods PubMed and Google Scholar were searched for articles in the English language regarding epithelial ovarian cancer, obesity, diabetes mellitus, and metabolic syndrome, with a focus on studies conducted since 1990. Results Obesity, type II diabetes mellitus, and metabolic syndrome have been associated with poor outcomes in epithelial ovarian cancer. More studies investigating the relationship between metabolic syndrome and epithelial ovarian cancer are needed. A variety of pathologic factors may contribute to cancer risk in patients with metabolic derangements, including altered adipokine and cytokine expression, altered immune responses to tumor cells, and changes in pro-tumorigenic signaling pathways. Conclusion More research is needed to examine the effects of metabolic syndrome on epithelial ovarian cancer risk and mortality, as well as the underlying pathophysiologies in patients with obesity, diabetes mellitus, and metabolic syndrome that may be targeted for therapeutic intervention.

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“…This effect is likely due to its activity at the insulin-like growth factor-1 receptor, promoting proliferation and angiogenesis, which can be demonstrated by the positive correlation between diabetes and breast and gynaecological cancers. 15 Insulin-mediating effects of metformin, then, show evidence of reducing incidence and improving survival among these malignancies, although the evidence is mixed. 16 17 The link between insulin resistance and cell proliferation offers an intriguing potential therapeutic target to reverse hyperplasia and prevent endometrial carcinoma.…”

Section: Description Of the Interventionmentioning

confidence: 99%

Metformin for endometrial hyperplasia: a Cochrane protocol

et al. 2016

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IntroductionEndometrial hyperplasia is a precancerous lesion of the endometrium, commonly presenting with uterine bleeding. If managed expectantly, it frequently progresses to endometrial carcinoma, rates of which are increasing dramatically worldwide. However, the established treatment for endometrial hyperplasia (progestogens) involves multiple side effects and leaves the risk of recurrence. Metformin is the most commonly used oral hypoglycaemic agent in type 2 diabetes mellitus. It has also been linked to the reversal of endometrial hyperplasia and may therefore contribute to decreasing the prevalence of endometrial carcinoma without the fertility and side effect consequences of current therapies. However, the efficacy and safety of metformin being used for this therapeutic target is unclear and, therefore, this systematic review will aim to determine this.Methods and analysisWe will search the following trials and databases with no language restrictions: Cochrane Gynaecology and Fertility Specialised Register; Cochrane Central Register of Controlled Trials (CENTRAL); MEDLINE; EMBASE; EBSCO Cumulative Index to Nursing and Allied Health Literature; PubMed; Google Scholar; ClinicalTrials.gov; the WHO International Trials Registry Platform portal; OpenGrey and the Latin American and Caribbean Health Sciences Literature (LILACS). We will include randomised controlled trials (RCTs) of use of metformin compared with a placebo or no treatment, conventional medical treatment (eg, progestogens) or any other active intervention. Two review authors will independently assess the trial eligibility, risk of bias and extract appropriate data points. Trial authors will be contacted for additional data. The primary review outcome is the regression of endometrial hyperplasia histology towards normal histology. Secondary outcomes include hysterectomy rate; abnormal uterine bleeding; quality of life scores and adverse reactions to treatments.Ethics and disseminationDissemination of the completed review will be through the Cochrane Library as well as through presenting the results at appropriate conferences.

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Diabetes mellitus and gynecologic cancer: molecular mechanisms, epidemiological, clinical and prognostic perspectives

Abstract: Diabetes mellitus is associated with an elevation in gynecologic cancer risk. Moreover, there are many studies exploring the prognosis of patients with diabetes and gynecological cancer, the outcome and the overall survival in well-regulated patients.

Cited by 56 publications

References 74 publications

Hypodontia and ovarian cancer: A systematic review

Hypodontia and ovarian cancer: A systematic review

Metabolic risk factors and mechanisms of disease in epithelial ovarian cancer: A review

Metformin for endometrial hyperplasia: a Cochrane protocol

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