Adiposity and cancer risk: new mechanistic insights from epidemiology

Renehan, Andrew G; Zwahlen, Marcel; Egger, Matthias

doi:10.1038/nrc3967

Cited by 525 publications

(461 citation statements)

References 166 publications

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“…There is a complex array of biological mechanisms through which obesity may influence prostate carcinogenesis and metastasis, including hyperinsulinemia, elevated insulin-like growth factor (IGF) hormone levels, dysregulation of sex steroid hormones, altered levels of adipokines, and chronic inflammation (3,44). Hyperinsulinemia has been associated with increased circulating levels of IGF-1, which have been found to promote carcinogenesis, including within the prostate (45)(46)(47).…”

Section: Articlementioning

confidence: 99%

Prediagnostic Body Mass Index Trajectories in Relation to Prostate Cancer Incidence and Mortality in the PLCO Cancer Screening Trial

Kelly

Graubard

Andreotti³

et al. 2016

JNCI J Natl Cancer Inst

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Background: Evidence suggests that obesity in adulthood is associated with increased risk of "clinically significant" prostate cancer. However, studies of body mass index (BMI) across the adult life course and prostate cancer risks remain limited. Methods: In a prospective cohort of 69 873 men in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial, we examined associations of prediagnostic BMI across the adult life course with risk of incident prostate cancer and fatal prostate cancer (prostate cancer-specific mortality). At 13 years of follow-up, we identified 7822 incident prostate cancer cases, of which 3078 were aggressive and 255 fatal. BMI trajectories were determined using latent-class trajectory modeling. Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Results: BMI at age 20 years, 50 years, and baseline questionnaire (mean age ¼ 63 years) were associated with increased risks of fatal prostate cancer (HRs ¼ 1.27-1.32 per five-unit increase). In five BMI trajectories identified, fatal prostate cancer risk was increased in men who had a normal BMI (HR ¼ 1.95, 95% CI ¼ 1.21 to 3.12) or who were overweight (HR ¼ 2.65, 95% CI ¼ 1.35 to 5.18) at age 20 years and developed obesity by baseline compared with men who maintained a normal BMI. Aggressive and nonaggressive prostate cancer were not associated with BMI, and modest inverse associations were seen for total prostate cancer. Conclusions: Our results suggest that BMI trajectories during adulthood that result in obesity lead to an elevated risk of fatal prostate cancer.

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Section: Articlementioning

confidence: 99%

Prediagnostic Body Mass Index Trajectories in Relation to Prostate Cancer Incidence and Mortality in the PLCO Cancer Screening Trial

Kelly

Graubard

Andreotti³

et al. 2016

JNCI J Natl Cancer Inst

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“…In a meta-analysis including 20 studies, Renehan et al 75 reported an overall decrease in risk of 8% (95% CI: −12 to −3) for each increment of 5 kg/m 2 in BMI. While BMI is a valid parameter for general adiposity, it does not reflect the visceral fat deposit and WC, and WHR provides a better proxy of abdominal adipose tissue, which appears to be more metabolically active than peripheral adipose tissue 25,76 .…”

Section: Body Fatnessmentioning

confidence: 99%

The Role of Diet, Physical Activity, Body Fatness, and Breastfeeding in Breast Cancer in Young Women: Epidemiological Evidence

Romieu

Amadou

Chajès

2017

RIC

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The incidence of breast cancer (BC) is rising worldwide, with an increase in aggressive neoplasias in young women. Traditionally, BC in young women has been thought to be etiologically driven, primarily by genetic/hereditary factors. However, these factors explain only a small proportion of BCs, pointing to a role of the environment. Suspected factors responsible for this increase include lifestyle changes, notably alcohol consumption, diet with high intake of refined carbohydrates and saturated fat and low intake of polyunsaturated fatty acids (PUFA), fiber and vitamins (such as folate, vitamin D, and carotenoids), low physical activity, and body fatness, all of which may act from childhood and adolescent years through adulthood. Despite limited data on BC in young women, evidence points to the importance of a healthy lifestyle, including high intake of vegetables, fruits, legumes, fish, and poultry, low intake of sugar and fat, daily physical activity, low alcohol consumption, steady weight, and breastfeeding in preventing BC in young women. Preventive efforts should begin in early life to provide important benefits much later in life by shifting the long-term trajectory of risk accumulation. Data from Latin America and developing regions are still sparse. There is a need to harmonize studies in a global effort to fight the rise of BC incidence in low-and middle-income countries, where the nutritional transition is occurring rapidly. The stratification of BC by specific tumor characteristics needs to be considered since risk factors may be more particularly associated with the promotion of, or protection from, a defined type of BC.

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“…In solid malignancies, the hypoxic conditions found at the core of the tumors induce adaptive pathways aimed at maintaining lipid synthesis, homeostatic pH and cell survival [6]. The resulting metabolic changes correlate with poor prognosis, poor treatment response and recurrence in diseases such as breast, liver and brain cancer [7][8][9][10]. Emerging therapeutic approaches have thus targeted lipid synthesis to counter the effects of metabolic reprogramming in cancer cells [11,12].…”

Section: Introductionmentioning

confidence: 99%

Pharmacological inhibition of lipid droplet formation enhances the effectiveness of curcumin in glioblastoma

Zhang

Cui

Amiri

et al. 2016

European Journal of Pharmaceutics and Biopharmaceutics

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a b s t r a c tIncreased lipid droplet number and fatty acid synthesis allow glioblastoma multiforme, the most common and aggressive type of brain cancer, to withstand accelerated metabolic rates and resist therapeutic treatments. Lipid droplets are postulated to sequester hydrophobic therapeutic agents, thereby reducing drug effectiveness. We hypothesized that the inhibition of lipid droplet accumulation in glioblastoma cells using pyrrolidine-2, a cytoplasmic phospholipase A2 alpha inhibitor, can sensitize cancer cells to the killing effect of curcumin, a promising anticancer agent isolated from the turmeric spice. We observed that curcumin localized in the lipid droplets of human U251N glioblastoma cells. Reduction of lipid droplet number using pyrrolidine-2 drastically enhanced the therapeutic effect of curcumin in both 2D and 3D glioblastoma cell models. The mode of cell death involved was found to be mediated by caspase-3. Comparatively, the current clinical chemotherapeutic standard, temozolomide, was significantly less effective in inducing glioblastoma cell death. Together, our results suggest that the inhibition of lipid droplet accumulation is an effective way to enhance the chemotherapeutic effect of curcumin against glioblastoma multiforme.

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Adiposity and cancer risk: new mechanistic insights from epidemiology

Cited by 525 publications

References 166 publications

Prediagnostic Body Mass Index Trajectories in Relation to Prostate Cancer Incidence and Mortality in the PLCO Cancer Screening Trial

Prediagnostic Body Mass Index Trajectories in Relation to Prostate Cancer Incidence and Mortality in the PLCO Cancer Screening Trial

The Role of Diet, Physical Activity, Body Fatness, and Breastfeeding in Breast Cancer in Young Women: Epidemiological Evidence

Pharmacological inhibition of lipid droplet formation enhances the effectiveness of curcumin in glioblastoma

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