Obesity-associated Cancer Risk Research Articles

Obesity-associated cancer risk reduction after metabolic surgery: insights from the SPLENDID study and the path forward.

Obesity incidence continues to rise globally along with obesity-associated conditions, which heavily burden individuals' quality of life and healthcare systems. Evidence regarding the power of metabolic and bariatric surgery to treat obesity has, fortunately, brought to light how substantial and sustained weight loss can mitigate adverse clinical outcomes of obesity and metabolic disease. Obesity-associated cancer has been an important focus of studies in recent decades to further elucidate what impact metabolic surgery could have on incidence of cancer and cancer-related mortality. The SPLENDID (Surgical Procedures and Long-term Effectiveness in Neoplastic Disease Incidence and Death) study is one of the recent large cohort studies that highlights the power of substantial weight loss and the long-term benefits to patients with obesity in preventing cancer. This review of SPLENDID aims to highlight both consistency of results with prior studies and new findings unexplored previously.

Understanding the mechanisms underlying obesity in remodeling the breast tumor immune microenvironment: from the perspective of inflammation.

Obesity is a well-known modifiable risk factor for breast cancer and is considered a poor prognostic factor in pre- and post-menopausal women. While the systemic effects of obesity have been extensively studied, less is known about the mechanisms underlying obesity-associated cancer risk and the local consequences of obesity. Thus, obesity-induced inflammation has become the focus of research interest. Biologically, the development of cancer involves a complex interaction with numerous components. As the tumor immune microenvironment changes due to obesity-triggered inflammation, an increase in infiltration occurs for proinflammatory cytokines and adipokines, as well as adipocytes, immune cells, and tumor cells in the expanded adipose tissue. Complicated cellular-molecular crosstalk networks change critical pathways, mediate metabolic and immune function reprogramming, and have a significant role in tumor metastasis, proliferation, resistance, angiogenesis, and tumorigenesis. This review summarizes recent research findings on how inflammatory mediators in the in situ tumor microenvironment regulate the occurrence and development of breast cancer in the context of obesity. We analyzed the heterogeneity and potential mechanisms of the breast cancer immune microenvironment from the perspective of inflammation to provide a reference for the clinical transformation of precision targeted cancer therapy.

Awareness of link between obesity and breast cancer risk is associated with willingness to participate in weight loss intervention

PurposeTo assess knowledge of obesity-associated cancer risk, self-awareness of BMI status, and willingness to engage in weight loss intervention in breast cancer survivors with overweight and obesity as a companion study for a novel weight loss program using a telehealth platform (NCT04855552).MethodsBreast cancer survivors with BMI ≥ 25 kg/m2 were surveyed to assess self-perception of BMI, knowledge of obesity-related cancer risk, and willingness to participate in weight loss programs. Multivariable logistic regression was used to assess factors associated with willingness to participate.ResultsOf the 122 participants, 73 (59.8%) had BMI 25.0–29.9 kg/m2 (overweight) and 49 (40.2%) had BMI ≥ 30 (obesity). Patients with obesity were more likely to underestimate their BMI than those with overweight, 40.8% vs. 23.3% (p = 0.03). The majority (82.0%) indicated awareness that obesity increases breast cancer risk and 57.4% expressed interest in a weight loss program. Patients with knowledge of obesity-related breast cancer risk (91.4% willing vs. 69.2% not willing, p < 0.01) were more willing to participate in a weight loss program on univariable and multivariable analyses (p < 0.01).ConclusionOur results underscore the importance of raising patients’ awareness of obesity-related health risks and individual BMI category. Future work in the development of better education and communication tools to improve awareness will likely improve the adoption rate of healthy lifestyles in at-risk patients.Supplementary InformationThe online version contains supplementary material available at 10.1007/s10549-022-06546-y.

Insulin/IGF-1 Signaling Is Downregulated in Barrett's Esophagus Patients Undergoing a Moderate Calorie and Protein Restriction Program: A Randomized 2-Year Trial.

Obesity and associated insulin resistance (Ins-R) have been identified as important risk factors for esophageal adenocarcinoma development. Elevated calories and protein consumption are also associated with Ins-R and glucose intolerance. We investigated the effect of a 24-month moderate calorie and protein restriction program on overweight or obese patients affected by Barrett’s esophagus (BE), as no similar dietary approach has been attempted to date in this disease context. Anthropometric parameters, levels of serum analytes related to obesity and Ins-R, and the esophageal insulin/IGF-1 signaling pathway were analyzed. This study is registered with ClinicalTrials.gov, number NCT03813381. Insulin, C-peptide, IGF-1, IGF-binding protein 3 (IGFBP3), adipokines, and esophageal expression of the main proteins involved in insulin/IGF-1 signal transduction were quantified using Luminex-XMAP® technology in 46 patients who followed the restriction program (IA) and in 54 controls (CA). Body mass index and waist circumference significantly decreased in 76.1% of IA and 35.2% of CA. IGF-1 levels were reduced in 71.7% of IA and 51.8% of CA. The simultaneous reduction of glycaemia, IGF-1, the IGF-1/IGFBP3 ratio, and the improvement in weight loss-dependent insulin sensitivity, were associated with the downregulation of the insulin/IGF-1 signal on BE tissue. The proposed intervention program was an effective approach to counteract obesity-associated cancer risk factors. The improvement in metabolic condition resulted in a downregulation of the ERK-mediated mitogenic signal in 43.5% of patients, probably affecting the molecular mechanism driving adenocarcinoma development in BE lesions.

The role of immune dysfunction in obesity-associated cancer risk, progression, and metastasis.

Obesity has been linked to an increased risk of and a worse prognosis for several types of cancer. A number of interrelated mediators contribute to obesity's pro-tumor effects, including chronic adipose inflammation and other perturbations of immune cell development and function. Here, we review studies examining the impact of obesity-induced immune dysfunction on cancer risk and progression. While the role of adipose tissue inflammation in obesity-associated cancer risk has been well characterized, the effects of obesity on immune cell infiltration and activity within the tumor microenvironment are not well studied. In this review, we aim to highlight the impact of both adipose-mediated inflammatory signaling and intratumoral immunosuppressive signaling in obesity-induced cancer risk, progression, and metastasis.

An Insight on Selective Signaling Pathways Linking Obesity and Cancer

Obesity associated cancer is an important health issue. Major risk factors of obesity leading to cancer, through multiple signaling pathways, are insulin, insulin like growth factors, adipokines, and cytokines which are released from adipose tissue. The important signaling pathways are phosphoinositide 3-kinase (PI3K/ Akt), mitogen-activated protein kinase (MAPK) and signal transducer and activator of transcription 3 (STAT3). The PI3K/Akt and MAPK pathways have downstream effect on mammalian target of rapamycin (mTOR) leading to obesity associated cancer. Recent studies mostly focus on inhibition of mTOR for cancer therapy. It is essential to focus on PI3K/Akt, MAPK and STAT3 pathways which are under the impact of many cancer risk factors in obesity. Thus, signaling pathways may provide a novel approach for obesity associated cancer risk. In this review the signaling pathways linking obesity associated cancer are summarized.

Association between Dietary Energy Density and Obesity-Associated Cancer: Results from the Women’s Health Initiative

BackgroundDietary energy density (DED) is the ratio of energy (kilocalories or kilojoules) intake to food weight (grams) and is a measure of diet quality. Consumption of foods high in DED has been associated with weight gain in adults. ObjectiveTo investigate the association between baseline DED and incident obesity-associated cancers in the Women’s Health Initiative. DesignProspective cohort study of clinical trial and observational study participants. Participants/settingPostmenopausal women aged 50 to 79 years (N=92,295) enrolled in the observational study or the calcium and vitamin D trial and hormone replacement therapy trials of the Women’s Health Initiative. Main outcome measuresIncident, medical record-adjudicated, obesity-related cancers during follow-up. Exposure variable was DED (kilocalories per gram for the total diet) from self-reported dietary intake at baseline using a food frequency questionnaire. Statistical analysesThe associations between DED and each incident cancer, or any obesity-related cancer, were examined using competing-risks regression models, with death as a competing risk. Body mass index-stratified models were generated to investigate body mass index as a potential modifying factor. ResultsDED was associated with higher body mass index (28.9±6.0 vs 26.3±4.9) and waist circumference (89.3±14.2 vs 82.4±12.4 cm) for DED quintiles 5 vs 1, respectively. DED was associated with a 10% increased risk of any obesity-related cancer (subhazard ratioQ5 vs Q1: 1.1, 95% CI 1.03 to 1.2; P=0.004). This increased risk appeared limited to women who were normal weight at enrollment. ConclusionsHigher DED may be a contributing factor for obesity-related cancers, especially among normal-weight postmenopausal women and, as such, could serve as a modifiable behavior for dietary interventions to reduce obesity-associated cancer risk.

Hormonal Contraceptives for Endometrial Cancer Prevention in Obese and High-Risk Women in Virginia.

Endometrial cancer remains the fourth most common malignancy among US women, and hormonal contraceptives drastically reduce this risk. The study objectives were to assess the prescribing patterns, counseling practices, and knowledge of family physicians and obstetrician/gynecologists (OB/GYNs) regarding hormonal contraceptives, obesity, and cancer prevention. A 25-question survey was mailed to 4600 OB/GYNs and family practitioners licensed in Virginia to assess self-reported hormonal contraceptive prescription practices, patient evaluation and counseling, and gynecologic oncology knowledge. χ2 and t tests were used to assess for differences across groups. P < 0.05 was deemed significant. In total, 392 (9%) surveys were returned, with 256 (6%) being complete for analysis. The mean physician age was 53.6 years, 50.2% were men, and 92.6% of physicians prescribed hormonal contraception. Most physicians recognized decreased endometrial cancer risk associated with oral contraceptive pills (73.0%) and increased risk with obesity (95.3%), but only 36.7% consistently counseled patients on obesity-associated cancer risk. Compared with family physicians, OB/GYNs were more likely to cite endometrial cancer prevention as an indication for hormonal contraceptives (53.3% vs 10.9%, P < 0.0001); more often counseled patients on obesity-related cancer risk (P = 0.003); and were more likely to correctly identify Lynch syndrome (69.4% vs 22.5%, P < 0.0001), diabetes mellitus (85.2% vs 38.8%, P < 0.0001), and hypertension (41.7% vs 10.1%, P < 0.0001) as risk factors for endometrial cancer. Endometrial or ovarian cancer prevention factored into <2% of total hormonal contraception prescriptions; however, OB/GYN physicians were more likely to prescribe for those indications than family physicians (P = 0.005 and P < 0.001, respectively). Family physicians and OB/GYNs could improve their knowledge of endometrial cancer risk factors and the use of hormonal contraception for chemoprevention. This represents a significant opportunity for both specialties to optimize primary endometrial cancer prevention in their increasingly obese and at-risk female patients.

Hormonal Contraceptive Use for Endometrial Cancer Prevention

INTRODUCTION: Hormonal contraception decreases the risk of both endometrial and ovarian cancer. The study objectives were to assess the prescribing patterns, counseling practices, and knowledge of primary care physicians with regard to hormonal contraceptives and cancer prevention. METHODS: A 25-question survey was mailed to 4,600 obstetrician–gynecologists and family practitioners in a single state. RESULTS: Three hundred sixty-five (8%) surveys were returned with 236 (5%) complete for analysis. Mean physician age was 56.3 years, 51.4% were male, and 93.6% of physicians prescribe hormonal contraception. Most physicians recognized decreased endometrial cancer risk associated with oral contraceptive pills (73.6%) and increased risk with obesity (95.5%); only 36.8% consistently counsel patients on obesity-associated cancer risk. Compared with family physicians, obstetrician–gynecologists were more likely to prescribe hormonal contraception (99% compared with 88.9%; P=.002), cite endometrial or ovarian cancer prevention as an indication (51.5% compared with 11.1% and 47.5% compared with 9.4%, respectively; P<.001), more often counseled patients on obesity-related cancer risk (P=.012), and were more likely to correctly identify Lynch syndrome (69.3% compared with 23.9%; P<.001), diabetes (84.2% compared with 41.9%; P<.001), and hypertension (41.6% compared with 9.4%; P<.001) as endometrial cancer risk factors. Endometrial and ovarian cancer prevention as an indication for hormonal contraception factored into less than 1% of total prescriptions. CONCLUSIONS: Although obstetrician–gynecologists had greater understanding of endometrial cancer risks than family practitioners, hormonal contraceptives were rarely prescribed for prevention. This represents a potential opportunity for both specialties to optimize primary endometrial cancer prevention in at-risk women.

The microbiome and obesity-an established risk for certain types of cancer.

Obesity is a major modifiable risk factor for the development of numerous types of cancer. Although many factors contribute to obesity-driven tumorigenesis, this review focuses on the functioning of the gut microbiota (the microbiome) as an environmental risk factor for certain types of cancers, and presents possible biological mediators. Obesity is a well-studied condition that is associated with microbiotal dysbiosis, which could result in several physiologic changes that may contribute to the relationship between obesity and cancer risk. These include altered microbial metabolism, which contributes to the generation of procarcinogenic toxic metabolites; increased extraction of energy and nutrient availability leading to metabolic dysregulation that contributes to tumor growth; and/or the induction of subclinical inflammation initiating tumorigenesis. Thus, the gut microbiota may serve as a key link between obesity and cancer and, therefore, viable strategies to alter the microbiota may provide novel therapeutics to reduce obesity-associated cancer risk.