The relationship between aging and carcinogenesis: a critical appraisal

Anisimov, Vladimir N.

doi:10.1016/s1040-8428(02)00121-x

Cited by 87 publications

(64 citation statements)

References 236 publications

(213 reference statements)

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“…All these predictors are known for the relation with developing endometrial cancer (Smith et al, 2003;Beral et al, 2005;Lesko et al, 1985;Hinkula et al, 2002;Kitson et al, 2017). The relation between age and the development of several types of cancer has been most extensively described (DePinho, 2000;Balducci and Ershler, 2005;Anisimov, 2003). In the diagnostic models clinical predictors were more important, such as endometrial thickness, recurrent bleeding and insulin resistance.…”

Section: Discussionmentioning

confidence: 99%

Prediction models for endometrial cancer for the general population or symptomatic women: A systematic review

Alblas

Velt

Pashayan

et al. 2018

Critical Reviews in Oncology/Hematology

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Objective: To provide an overview of prediction models for the risk of developing endometrial cancer in women of the general population or for the presence of endometrial cancer in symptomatic women. Methods: We systematically searched the Embase and Pubmed database until September 2017 for relevant publications. We included studies describing the development, the external validation, or the updating of a multivariable model for predicting endometrial cancer in the general population or symptomatic women. Results: Out of 2756 references screened, 14 studies were included. We found two prediction models for developing endometrial cancer in the general population (risk models) and one extension. Eight studies described the development of models for symptomatic women (diagnostic models), one comparison of the performance of two diagnostic models and two external validation. Sample size varied from 60 (10 with cancer) to 201,811 (855 with cancer) women. The age of the women was included as a predictor in almost all models. The risk models included epidemiological variables related to the reproductive history of women, hormone use, BMI, and smoking history. The diagnostic models also included clinical predictors, such as endometrial thickness and recurrent bleeding. The concordance statistic (c), assessing the discriminative ability, varied from 0.68 to 0.77 in the risk models and from 0.73 to 0.957 in the diagnostic models. Methodological information was often limited, especially on the handling of missing data, and the selection of predictors. One risk model and four diagnostic models were externally validated. Conclusions: Only a few models have been developed to predict endometrial cancer in asymptomatic or symptomatic women. The usefulness of most models is unclear considering methodological shortcomings and lack of external validation. Future research should focus on external validation and extension with new predictors or biomarkers, such as genetic and epigenetic markers.

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Section: Discussionmentioning

confidence: 99%

Prediction models for endometrial cancer for the general population or symptomatic women: A systematic review

Alblas

Velt

Pashayan

et al. 2018

Critical Reviews in Oncology/Hematology

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“…Such findings are likely related to the fact that aging, in addition to prior exposure to chemotherapy and radiation, often facilitates carcinogenesis. [2,32,33] Previous research [34] reported that the prevalence of hypertension and diabetes among women is highest in the older age groups. The results in this study support the findings of Yancik et al [35] and Barbieri[36] that the prevalence of hypertension and diabetes actually begins to decline in the oldest age cohorts.…”

Section: Discussionmentioning

confidence: 99%

The changing prevalence of comorbidity across the age spectrum

Piccirillo¹,

Vlahiotis²,

Barrett³

et al. 2008

Critical Reviews in Oncology/Hematology

270

151

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The purpose of the research was to demonstrate that comorbid health conditions disproportionately affect elderly cancer patients. Descriptive analyses and stacked area charts were used to examine the prevalence and severity of comorbid ailments by age of 27,506 newly diagnosed patients treated at one of eight cancer centers between 1998 and 2003. Hypertension was the most common ailment in all patients, diabetes was the second most prevalent ailment in middle-aged patients, and previous solid tumor(s) were the second most prevalent ailment in patients aged 74 and older. Although the prevalence and severity of comorbid ailments including dementia and congestive heart failure increased with age, some comorbidities such as HIV/AIDS and obesity decreased. Advances in cancer interventions have increased survivorship, but the impact of the changing prevalence and severity of comorbidities at different ages has implications for targeted research into targeted clinical and psychosocial interventions.

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“…For example, liver carcinoma cells transplanted into livers of young rats differentiate into hepatocytes; in contrast, when the same cells are transplanted into livers of old animals, these cells produce tumors consisting of undifferentiated cells [92]. In fact, agerelated changes in tissue environment substantially affect carcinogen induced tumorigenesis in many rodent model systems [93]. Moreover, one of the consequences of aging is the accumulation of senescent cells in many tissues [94][95][96], and senescent cells secrete a number of active molecules that can promote tumor growth [97,98].…”

Section: The Complex Relationship Between Aging Carcinogen Exposure mentioning

confidence: 99%

Declining cellular fitness with age promotes cancer initiation by selecting for adaptive oncogenic mutations

Marusyk

DeGregori

2008

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer

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SummaryAge is the single most important prognostic factor in the development of many cancers. The major reason for this age-dependence is thought to be the progressive accumulation of oncogenic mutations and epigenetic changes. Similarly, mutagens are thought to be carcinogenic primarily by engendering oncogenic mutations. Yet while the accumulation of heritable somatic changes is expected to augment the incidence of oncogenic mutations, a major effect of increased mutation load is reduced fitness. We propose that the fitness of progenitor cell compartments substantially impacts on the selective advantage conferred by particular mutations. We hypothesize that reduced cellular fitness within aged stem cell pools can select for adaptive oncogenic events and thereby promote the initiation of cancer. Thus, certain oncogenic mutations may be adaptive within aged but not young stem cell pools. We further argue that accumulating genetic alterations with age or mutagen exposure might promote cancer not only by causing oncogenic hits within cells but also by leading to eventual reduction in stem cell fitness, which then selects for oncogenic events. Therefore, initial stages of cancer development may not be limited by the incidence of initiating oncogenic changes, but instead by contexts of reduced cellular fitness that select for these changes.

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The relationship between aging and carcinogenesis: a critical appraisal

Cited by 87 publications

References 236 publications

Prediction models for endometrial cancer for the general population or symptomatic women: A systematic review

Prediction models for endometrial cancer for the general population or symptomatic women: A systematic review

The changing prevalence of comorbidity across the age spectrum

Declining cellular fitness with age promotes cancer initiation by selecting for adaptive oncogenic mutations

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