Sex disparity in the association between metabolic-anthropometric phenotypes and risk of obesity-related cancer: a prospective cohort study.

BACKGROUND: Sex disparity between metabolic-obesity (defined by body mass index, BMI) phenotypes and obesity-related cancer (ORC) remains unknown. Considering BMI reflecting overall obesity but not fat distribution, we aimed to systematically assess the association of our newly proposed metabolic-anthropometric phenotypes with risk of overall and site-specific ORC by sex. METHODS: A total of 141,579 men (mean age: 56.37 years, mean follow-up time: 12.04 years) and 131,047 women (mean age: 56.22 years, mean follow up time: 11.82 years) from the UK Biobank was included, and designated as metabolic-anthropometric phenotypes based on metabolic status (metabolically healthy/unhealthy), BMI (non-obesity/obesity) and body shape (pear/slim/apple/wide). The sex-specific association of different phenotypes with overall and site-specific ORC was assessed by hazard ratios (HRs) and 95% confidence intervals (CIs) using Cox proportional hazards regression models. RESULTS: We found metabolically unhealthy and/or obesity phenotypes conveyed a higher risk in men than in women for overall ORC and colorectal cancer compared with metabolically healthy non-obesity phenotype (Pinteraction < 0.05). Of note, metabolically healthy obesity phenotype contributed to increased risks of most ORC in men (HRs: 1.58 ~ 2.91), but only correlated with higher risks of endometrial (HR = 1.89, 95% CI: 1.54-2.32) and postmenopausal breast cancers (HR = 1.17, 95% CI: 1.05-1.31) in women. Similarly, even under metabolically healthy, men carrying apple and wide shapes phenotypes (metabolically healthy apple/wide and metabolically healthy non-obesity apple/wide) suffered an increased risk of ORC (mainly colorectal, liver, gastric cardia, and renal cancers, HRs: 1.20 ~ 3.81) in comparison with pear shape or non-obesity pear shape. CONCLUSIONS: There was a significant sex disparity between metabolic-anthropometric phenotypes and ORC risk. We advised future ORC prevention and control worth taking body shape and sex disparity into account.

Dietary carbohydrate quality index and incidence of obesity-related cancers in the "Seguimiento Universidad De Navarra" (SUN) prospective cohort.

PURPOSE: The quality, rather than the quantity, of carbohydrate intake may play a major role in the etiology of obesity-related cancers (ORCs). We assessed the association between a previously defined carbohydrate quality index (CQI) and the risk of developing ORCs in the "Seguimiento Universidad de Navarra" (SUN) cohort. METHODS: A total of 18,446 Spanish university graduates [mean age 38 years (SD 12 years), 61% women, mean BMI 23.5 kg/m2 (SD 3.5 kg/m2)], with no personal history of cancer, were followed-up. Baseline CQI was assessed summing quintiles of four previously defined criteria: high dietary fiber intake, low glycemic index (GI), high whole-grain: total-grain carbohydrates ratio and high solid carbohydrates: total carbohydrates ratio. Participants were classified into tertiles of their total CQI. Incident ORCs were confirmed by an oncologist using medical records and by querying the National Death Index blindly to dietary exposures. RESULTS: During a median follow-up of 13.7 years, 269 incident cases of ORC were confirmed. A higher CQI was inversely associated with ORC incidence [multivariable-adjusted hazard ratio (HR) for the upper (T3) versus the lowest tertile (T1) of 0.68 (95% CI: 0.47-0.96), p for trend = 0.047]. Particularly, higher dietary fiber intake was inversely associated with ORC, HRT3 vs. T1=0.57 (95% CI 0.37-0.88 p for trend = 0.013). CONCLUSION: In this prospective Mediterranean cohort, an inverse association between a better global quality of carbohydrate intake and the risk of ORCs was found. Strategies for cancer prevention should promote a higher quality of carbohydrate intake.

Historical Obesity and Early-Onset Cancers: A Propensity-Weighted Analysis of the National Health and Nutrition Examination Survey.

BACKGROUND: The incidence of early-onset obesity-related cancers (diagnosed < 50 years) is increasing in the U.S. We examined the reported historical body mass index (BMI) of adults with early and later-onset cancers to explore relation to obesity. METHODS: We queried the 1999-2018 NHANES database for adults diagnosed with obesity-related cancers (colorectal, non-colorectal gastrointestinal, uterine, breast). We classified early and late-onset cancer based on a diagnosis age of < 50 and ≥ 50 years, respectively. Propensity-weighted analysis was used to compare prior historical BMIs between the matched groups. RESULTS: After weighing, we included 2,966,528 patients with obesity-related cancers, 846,211 (28%) of which were < 50 years. In the matched analysis, 69.1% of early-onset CRC cases were diagnosed as obese (BMI ≥ 30 kg/m2) before cancer diagnosis, compared to 47.2% of late-onset cases (p < 0.03). Similarly, a higher percentage of adults with other early-onset gastrointestinal cancers had prior obesity as compared to the late-onset cohort (70.3% vs. 40.5%, p = 0.0002). BMI showed a trend toward higher values at ages 20-24 for early-onset CRC and 30-34 for other gastrointestinal cancers. In contrast, later-onset CRC and other gastrointestinal cancers exhibited higher BMI values at later ages (30-34 and 35-39, respectively). Early-onset uterine cancer was linked to a higher BMI compared to later-onset cancer (34.0 vs. 31.1 kg/m2, p < 0.0001), with a trend towards a higher BMI before 19 years old. CONCLUSIONS: Our nationally representative data reveal that higher and earlier body fatness in adulthood associates with early-onset gastrointestinal and uterine cancers. These findings underscore the importance of intensifying efforts to combat early-life obesity.

Associations Between Cancer Risk Perceptions, Self-Efficacy, and Health Behaviors by BMI Category and Race and Ethnicity.

BACKGROUND: Cancer risk perceptions and high health-related self-efficacy may impact health behaviors and reduce risk of developing obesity-related cancers. The purpose of this study was to examine whether there are differences in associations among cancer risk perceptions, health-related self-efficacy, and health behaviors between people with healthy weight (PwHW) and people with overweight or obesity (PwO/O), and whether these associations vary by race and ethnicity. METHOD: Data from the Health Information National Trends Survey (HINTS) 5 Cycles 2 and 3 were used. Data from 6944 adults were analyzed using multivariate logistic regression to assess associations among study variables. RESULTS: PwO/O who believed there are too many cancer prevention recommendations had lower log odds of meeting guidelines for strength training (ß - 0.28; CI - 0.53 to - 0.04; p < 0.05) compared to PwHW. PwO/O who believed that obesity influences cancer risk were associated with low sedentary behavior (ß 0.29; CI 0.05-0.54; p < 0.05) compared to PwHW. NHB PwO/O who held fatalistic beliefs and reported high self-efficacy ordered less food (e.g., fewer food items, foods with less calories, or smaller food sizes) compared to NHB Pw/HW (p < 0.05). CONCLUSION: Health behavior differences in PwHW and PwO/O may be associated with differences in cancer risk beliefs and health-related self-efficacy. Findings support the need for further research considering BMI and race and ethnicity in obesity-related cancer prevention and control.

Interaction of leisure-time physical activity with body mass index on the risk of obesity-related cancers: A pooled study.

Physical activity (PA) has been associated with a lower risk of some obesity-related cancers, but the combined association and interaction of PA and body weight on obesity-related cancer risk is less clear. We examined the association of leisure-time PA (high/low) and its combination with body mass index (BMI, <25 [low]/≥25 [high] kg/m2 ) on obesity-related cancer risk in 570 021 individuals, aged 43 years on average at baseline, in five Scandinavian cohorts. We used Cox regression to calculate hazard ratios of obesity-related cancers (n = 19 074) and assessed multiplicative and additive interactions between PA and BMI on risk. High leisure-time PA, recorded in 19% of the individuals, was associated with a 7% (95% confidence interval [CI] 4%-10%) lower risk of any obesity-related cancer compared to low PA, with similar associations amongst individuals with a low and a high BMI (6% [1%-11%] and 7% [2%-11%]). High PA was also associated with decreased risks of renal cell (11% [9%-31%]) and colon cancer (9% [2%-16%]). When high PA and low BMI were combined, the relative risk reduction for all obesity-related cancers was 24% (95% CI 20%-28%); endometrial cancer, 47% (35%-57%); renal cell cancer, 39% (27%-51%); colon cancer, 27% (19%-35%); multiple myeloma, 23% (2%-40%) and pancreatic cancer, 21% (4%-35%), compared to low PA-high BMI. There were no additive or multiplicative interactions between PA and BMI on risk. The result of our study suggests a reduced risk of obesity-related cancer by leisure-time PA in both normal weight and overweight individuals, which further decreased for PA and normal weight combined.

Menstrual cycle characteristics and incident cancer: a prospective cohort study.

STUDY QUESTION: Are menstrual cycle characteristics throughout the reproductive lifespan associated with cancer risk? SUMMARY ANSWER: Irregular and long menstrual cycles throughout the reproductive lifespan were associated with increased risk of total invasive cancer, especially obesity-related cancers. WHAT IS KNOWN ALREADY: Long and irregular menstrual cycles have been associated with lower risk of pre-menopausal breast cancer and higher risk of endometrial cancer, but associations with other malignancies are less clear. STUDY DESIGN, SIZE, DURATION: Prospective cohort study. Prospective follow-up of 78 943 women participating in the Nurses' Health Study II between 1989 and 2015. PARTICIPANTS/MATERIALS, SETTING, METHODS: We followed 78 943 pre-menopausal women without cancer history who reported the usual length and regularity of their menstrual cycles at different ages (14-17, 18-22 and 29-46 years). Cancer diagnosis was confirmed through medical record review and classified as obesity-related (colorectal, gallbladder, kidney, multiple myeloma, thyroid, pancreatic, esophageal, gastric, liver, endometrial, ovarian and post-menopausal breast) or non-obesity-related. We fitted Cox proportional hazards models to estimate hazard ratios (HRs) and 95% CIs of the association between menstrual cycle characteristics and cancer incidence. MAIN RESULTS AND THE ROLE OF CHANCE: We documented 5794 incident cancer cases during 1 646 789 person-years of follow-up. After adjusting for BMI and other potential confounders, women reporting irregular cycles at age 29-46 years had an 11% (95% CI: 2-21%) higher risk of total invasive cancer than women reporting very regular cycles at the same age. This association was limited to obesity-related cancers, with a 23% (95% CI: 9-39%) higher risk and was strongest for endometrial cancer (HR = 1.39; 95% CI: 1.09-1.77). Findings were comparable for cycle characteristics earlier in life and for menstrual cycle length. Very irregular cycles at age 14-17 years were associated with significant increase in risk of colorectal cancer (HR = 1.36; 95% CI: 1.02-1.81). LIMITATIONS, REASONS FOR CAUTION: Our study might be subject to recall bias for findings pertaining to cycle characteristics in adolescence and early adulthood, as these were retrospectively reported. Generalizability to non-White women may be limited, as 96% of participants were White. WIDER IMPLICATIONS OF THE FINDINGS: Women with irregular or long menstrual cycles in mid-adulthood had a statistically significantly higher risk of developing cancer, especially obesity-related cancers. This association was not limited to gynecological cancers. Obesity-related cancers may need to be added to the spectrum of long-term health consequences of long or irregular cycles, possibly warranting targeted screening among women who experience long or irregular cycles in mid-adulthood. STUDY FUNDING/COMPETING INTEREST: This work was supported by grants U01 CA176726, U01 HL145386 and R01 HD096033 from the National Institutes of Health. The authors have no conflicts of interest to declare. TRIAL REGISTRATION NUMBER: N/A.

Leptin Signaling Affects Survival and Chemoresistance of Estrogen Receptor Negative Breast Cancer.

Estrogen-receptor-negative breast cancer (BCER-) is mainly treated with chemotherapeutics. Leptin signaling can influence BCER- progression, but its effects on patient survival and chemoresistance are not well understood. We hypothesize that leptin signaling decreases the survival of BCER- patients by, in part, inducing the expression of chemoresistance-related genes. The correlation of expression of leptin receptor (OBR), leptin-targeted genes (CDK8, NANOG, and RBP-Jk), and breast cancer (BC) patient survival was determined from The Cancer Genome Atlas (TCGA) mRNA data. Leptin-induced expression of proliferation and chemoresistance-related molecules was investigated in triple-negative BC (TNBC) cells that respond differently to chemotherapeutics. Leptin-induced gene expression in TNBC was analyzed by RNA-Seq. The specificity of leptin effects was assessed using OBR inhibitors (shRNA and peptides). The results show that OBR and leptin-targeted gene expression are associated with lower survival of BCER- patients. Importantly, the co-expression of these genes was also associated with chemotherapy failure. Leptin signaling increased the expression of tumorigenesis and chemoresistance-related genes (ABCB1, WNT4, ADHFE1, TBC1D3, LL22NC03, RDH5, and ITGB3) and impaired chemotherapeutic effects in TNBC cells. OBR inhibition re-sensitized TNBC to chemotherapeutics. In conclusion, the co-expression of OBR and leptin-targeted genes may be used as a predictor of survival and drug resistance of BCER- patients. Targeting OBR signaling could improve chemotherapeutic efficacy.

Weight change since age 20 and incident risk of obesity-related cancer in Japan: a pooled analysis of the Miyagi Cohort Study and the Ohsaki Cohort Study.

It is unclear whether weight change during adulthood affects the risk of obesity-related cancers such as those of the esophagus, colorectum, pancreas, breast, endometrium, and kidney among Japanese, where obesity is less frequent and less severe. We examined the association between weight change during adulthood and the risk of obesity-related cancer among Japanese by conducting a pooled analysis of two prospective studies of residents in Miyagi Prefecture, Japan. A total of 78,743 persons (40,422 women and 38,321 men) aged 40-79 years participated in the Miyagi Cohort Study in 1990 and in the Ohsaki Cohort Study in 1994. Weight change since age 20 was divided into four categories (weight loss; stable weight; moderate weight gain; high weight gain). Cox proportional hazards regression analysis was used to estimate the multivariate hazard ratios (HRs) and 95% confidence intervals (CIs) for obesity-related cancer incidence. During 1,057,899 person-years of follow up, 4,467 cases of obesity-related cancer (women; 1,916 cases, men; 2,551cases) were identified. In women, compared to the stable weight, weight gain was associated with an increased risk of obesity-related cancer (moderate weight gain; HRs = 1.10, 95%CIs: 0.97-1.26, high weight gain; HRs = 1.29, 95%CIs: 1.14-1.47). The results indicate that weight gain since age 20 was associated with a significantly increased risk of obesity-related cancer among Japanese women. By contrast, in men, our study found that weight change is not associated with the incidence of obesity-related cancer.

Excess Costs and Economic Burden of Obesity-Related Cancers in the United States.

BACKGROUND: Obesity is a significant risk factor of several cancers that imposes a substantial economic burden on US healthcare that remains to be quantified. We estimated the excess costs and economic burden of obesity-related cancers in the United States. METHODS: From the Medical Expenditure Panel Survey (2008-2015) data, we identified 19 405 cancer survivors and 175 498 non-cancer individuals. We estimated annual health expenditures using generalized linear regression with log link and gamma distribution by cancer types (stratified by 11 obesity-related cancers and other cancer types), controlling for sociodemographic and clinical characteristics. All cost estimates were adjusted to 2015 USD value. RESULTS: The average annual total health expenditures were $21 503 (95% CI, $20 946-$22 061) for those with obesity-related cancer and $13 120 (95% CI, $12 920-$13 319) for those with other cancer types. There was a positive association between body mass index and health expenditures among cancer survivors: for each additional 5-unit increase in body mass index, the average predicted expenditures increase by $1503 among those with obesity-related cancer and by $722 among those with other cancers. With adjustments for sociodemographic and clinical characteristics, the mean incremental expenditures of treating obesity-related cancer were 2.1 times higher than those of other cancers ($4492 vs $2139) and more considerable among the non-elderly cancer population. Obesity-related cancers accounted for nearly 43.5% of total direct cancer care expenditures, estimated at $35.9 billion in 2015. CONCLUSION: The economic burden of obesity-related cancer in the United States is substantial. Our findings suggest a need for the inclusion of comprehensive obesity prevention and treatment in cancer care.

Greenspace and risk of obesity-related cancer in the UK Biobank cohort: An analysis of private residential gardens and other greenspace types.

BACKGROUND: Cohort studies linking greenspace exposure to a lower risk of obesity-related cancer (ORC) are scarce. Existing evidence on site-specific cancers has predominantly relied on non-specific greenspace measures, including vegetation indices. We examined the associations of total greenspace, private residential gardens, and other greenspace types with the risk of being diagnosed with overall and site-specific ORC. METHODS: We used data from the participants in the UK Biobank recruited between 2006 and 2010 and censored until December 31, 2016. We defined greenspace variables using Ordnance Survey MasterMap™ greenspace categories. The incidence of ORC was ascertained through data linkage to cancer registries. Hazard ratios (HRs) and 95 % confidence intervals (CIs) were estimated using Cox proportional hazard models and adjusted for covariates. We conducted mediation and modification analysis by physical activity, serum 25-hydroxyvitamin D [25(OH)D], and particulate matter air pollution with an aerodynamic diameter ≤ 2.5 (PM2.5) and nitrogen dioxide (NO2), as well as subgroup analysis by covariates. RESULTS: Among 279,326 participants, 9550 developed ORC over a median follow-up period of 7.82 years. An increase in private residential gardens within a 100 m buffer was associated with a decreased risk of overall ORC (HR:0.92; 95 % CI: 0.88, 0.96), breast cancer (HR: 0.91; 95 % CI: 0.84, 0.98), and uterine cancer (HR:0.80; 95 % CI: 0.67, 0.96). There was no association between other greenspace types and ORC, except for uterine cancer. The association for ORC was partly mediated by NO2 and modified by physical activity levels, 25(OH)D, PM2.5, and NO2, and sociodemographic factors, including sex and neighbourhood socioeconomic status. CONCLUSION: Increased exposure to private residential gardens may lower the risk of being diagnosed with obesity-related cancer, particularly breast and uterine cancer. Future studies might move beyond considering greenspace quantity to explore functional types of greenspace exposure that should be prioritized for targeted health intervention and cancer prevention.

Inhibition of PPARγ by BZ26, a GW9662 derivate, attenuated obesity-related breast cancer progression by inhibiting the reprogramming of mature adipocytes into to cancer associate adipocyte-like cells.

Obesity has been associated with the development of 13 different types of cancers, including breast cancer. Evidence has indicated that cancer-associated adipocytes promote the proliferation, invasion, and metastasis of cancer. However, the mechanisms that link CAAs to the progression of obesity-related cancer are still unknown. Here, we found the mature adipocytes in the visceral fat of HFD-fed mice have a CAAs phenotype but the stromal vascular fraction of the visceral fat has not. Importantly, we found the derivate of the potent PPARγ antagonist GW9662, BZ26 inhibited the reprogramming of mature adipocytes in the visceral fat of HFD-fed mice into CAA-like cells and inhibited the proliferation and invasion of obesity-related breast cancer. Further study found that it mediated the browning of visceral, subcutaneous and perirenal fat and attenuated inflammation of adipose tissue and metabolic disorders. For the mechanism, we found that BZ26 bound and inhibited PPARγ by acting as a new modulator. Therefore, BZ26 serves as a novel modulator of PPARγ activity, that is, capable of inhibiting obesity-related breast cancer progression by inhibiting of CAA-like cell formation, suggesting that inhibiting the reprogramming of mature adipocytes into CAAs or CAA-like cells may be a potential therapeutic strategy for obesity-related cancer treatment.

Metabolic obesity phenotypes and obesity-related cancer risk in the National Health and Nutrition Examination Survey.

INTRODUCTION: Body mass index (BMI) fails to identify up to one-third of normal weight individuals with metabolic dysfunction who may be at increased risk of obesity-related cancer (ORC). Metabolic obesity phenotypes, an alternate metric to assess metabolic dysfunction with or without obesity, were evaluated for association with ORC risk. METHODS: National Health and Nutrition Examination Survey participants from 1999 to 2018 (N = 19,500) were categorized into phenotypes according to the metabolic syndrome (MetS) criteria and BMI: metabolically healthy normal weight (MHNW), metabolically unhealthy normal weight (MUNW), metabolically healthy overweight/obese (MHO) and metabolically unhealthy overweight/obese (MUO). Adjusted multivariable logistic regression models were used to evaluate associations with ORC. RESULTS: With metabolic dysfunction defined as ≥1 MetS criteria, ORC cases (n = 528) had higher proportions of MUNW (28.2% vs. 17.4%) and MUO (62.6% vs. 60.9%) phenotypes than cancer-free individuals (n = 18,972). Compared with MHNW participants, MUNW participants had a 2.2-times higher ORC risk [OR (95%CI) = 2.21 (1.27-3.85)]. MHO and MUO participants demonstrated a 43% and 56% increased ORC risk, respectively, compared to MHNW, but these did not reach statistical significance [OR (95% CI) = 1.43 (0.46-4.42), 1.56 (0.91-2.67), respectively]. Hyperglycaemia, hypertension and central obesity were all independently associated with higher ORC risk compared to MHNW. CONCLUSIONS: MUNW participants have a higher risk of ORC than other abnormal phenotypes, compared with MHNW participants. Incorporating metabolic health measures in addition to assessing BMI may improve ORC risk stratification. Further research on the relationship between metabolic dysfunction and ORC is warranted.

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.

Pre-diagnosis lipid levels and mortality after obesity-related cancer diagnosis in the Women's Health Initiative cardiovascular disease biomarker cohort.

BACKGROUND: Published studies have demonstrated inconclusive relationships between serum lipid levels and mortality after cancer. METHODS: The primary objective was to evaluate the relationship between fasting lipid levels and mortality after cancer. Data were obtained on baseline lipids and outcomes after cancer from 1263 postmenopausal women diagnosed with 13 obesity-related cancers who were part of the Women's Health Initiative (WHI) lipid biomarkers cohort. Obesity-related cancers included incident invasive cancers of the breast, colorectum, endometrium, esophagus (adenocarcinoma), kidney, liver, gallbladder, pancreas, ovaries, small intestine, thyroid, stomach, as well as multiple myeloma. Baseline lipid measurements included high-density lipoprotein (HDL)-cholesterol, low-density lipoprotein (LDL)-cholesterol, and non-HDL-cholesterol. Outcomes were all cause, cancer-specific, and CVD mortality. Multivariable Cox proportional hazards models were used to measure associations between lipid levels and mortality (all cause, cancer, and CVD) after a cancer diagnosis, with lipids analyzed as continuous variables. RESULTS: Among women with obesity-related cancer, there were 707 deaths, of which 379 (54%) were due to cancer and 113 (16%) were due to CVD. Mean time from blood draw to cancer diagnosis was 5.1 years (range: 0.05-10 years). LDL-C values above the 95th percentile were associated with higher risk of all-cause mortality (p < 0.001), and cancer-specific mortality (p < 0.001), but not mortality due to CVD. Non-HDL-C values above the 65th percentile were associated with higher risk of all-cause mortality (p = 0.01) and mortality due to CVD (p = 0.003), but not cancer-specific mortality (p = 0.37). HDL-C values above the 95th percentile were associated with lower all-cause mortality (p = 0.002), and above the 65th percentile with lower cancer-specific mortality (p = 0.003), but no significant relationship with mortality due to CVD was observed. CONCLUSIONS: The relationship between pre-diagnosis fasting lipid levels and mortality after cancer diagnosis is complex. These results suggest that improved lipid control through lifestyle and anti-lipid medications could have a meaningful impact on outcomes after cancer.

The effect of bariatric surgery on breast cancer incidence and characteristics: A meta-analysis and systematic review.

BACKGROUND: Obesity is a major risk factor for breast cancer. This study examines whether bariatric surgery affects breast cancer incidence in women with obesity compared to BMI-matched controls. METHODS: EMBASE, MEDLINE, Web of Science, and CINAHL were searched. Primary studies on female breast cancer incidence after bariatric surgery were eligible. RESULTS: 11 studies were included (n = 1,106,939). The rate of cancer diagnosis was lower in the surgical group (0.54%) compared to control (0.84%; risk ratio (RR) 0.50, 95%CI 0.37-0.67, I2 = 88%). The results were robust to sensitivity analyses for patient age and study size. Bariatric surgery was associated with increased risk of stage I cancer (RR 1.23, 95%CI 1.06-1.44) and reduced risk of stage III or IV cancer (RR 0.50, 95%CI 0.28-0.88). Hormone receptor characteristics were not affected. CONCLUSIONS: Bariatric surgery is associated with reduced incidence and earlier stage at diagnosis of breast cancer in women with obesity compared to BMI-matched controls.

Incidence of polyp formation following bariatric surgery.

BACKGROUND: Multiple studies have linked obesity to an increased risk of cancer. The correlation is so strong that the national cancer prevention guidelines recommend weight loss for patients with obesity to reduce their risk of cancer. Bariatric surgery has been shown to be very effective in sustained weight loss. However, there have been mixed findings about bariatric surgery and its effects on the risk of colorectal cancer. OBJECTIVE: This study sought to examine bariatric surgery patients and their risk of pre-cancerous or cancerous polyps to elucidate any risk factors or associations between bariatric surgery and colorectal cancer. SETTING: A retrospective review of the academic medical center's bariatric surgery database was performed from January 2010 to January 2017. Patients who underwent medical or surgical weight loss and had a subsequent colonoscopy were included in the study. Positive colonoscopy findings were described as malignant or premalignant polyps. METHODS: A total of 1777 patients were included, with 1360 in the medical group and 417 in the surgical group. Data analysis included patient demographics, co-morbidities, procedure performed, surgical approach, weight loss, and colonoscopy findings. A multivariate analysis was used to determine whether an association exists between weight loss and incidence of colorectal polyps, and if so, whether the association different for medical versus surgical weight loss. RESULTS: A higher percentage of body mass index (BMI) reduction was seen in the surgical group. An overall comparison showed average reductions in BMI of 27.7% in the surgical group and 3.5% in the medical group (P < .0001). Patients with the greatest reduction in BMI, regardless of medical or surgical therapy, showed a lower incidence of precancerous and cancerous polyps (P = .041). CONCLUSION: This study offers a unique approach in examining the incidence of colorectal polyps related to obesity. Patients with the greatest reduction in their BMI, more common in the surgical group, had a lower incidence of precancerous and cancerous polyps.

Development of cancer after bariatric surgery.

BACKGROUND: Although bariatric surgery has been associated with a reduction in risk of obesity-related cancer, data on the effect of bariatric interventions on other cancers are limited. OBJECTIVES: This study aimed to examine the relationship between bariatric interventions and the incidence of various cancers after bariatric surgery. SETTING: Administrative statewide database. METHODS: The New York Statewide Planning and Research Cooperative System database was used to identify all adult patients diagnosed with obesity between 2006 and 2012 and patients who underwent bariatric procedures without preexisting cancer diagnosis and alcohol or tobacco use. Subsequent cancer diagnoses were captured up to 2016. Multivariable proportional subdistribution hazard regression analysis was performed to compare the risk of having cancer among obese patients with and without bariatric interventions. RESULTS: We identified 71,000 patients who underwent bariatric surgery and 323,197 patients without a bariatric intervention. Patients undergoing bariatric surgery were less likely to develop both obesity-related cancer (hazard ratio.91; 95% confidence interval, .85-.98; P = .013) and other cancers (hazard ratio .81; 95% confidence interval, .74-.89; P < .0001). Patients undergoing Roux-en-Y gastric bypass had a lower risk of developing cancers that are considered nonobesity related (hazard ratio .59; 95% confidence interval, .42-.83; P = .0029) compared with laparoscopic sleeve gastrectomy. CONCLUSIONS: Bariatric surgery is associated with a decreased risk of obesity-related cancers. More significantly, we demonstrated the relationship between bariatric surgery and the reduction of the risk of some previously designated nonobesity-related cancers, as well. Reclassification of nonobesity-related cancers and expansion of bariatric indications for reducing the risk of cancer may be warranted.

Cancer Risk Following Bariatric Surgery-Systematic Review and Meta-analysis of National Population-Based Cohort Studies.

This study has analyzed results from registry-based population studies to assess the effect of bariatric surgery upon cancer incidence at a population level. Relevant studies were identified and meta-analysis was used to calculate pooled odds ratios (POR) for the incidence of cancer after bariatric surgery compared to controls. Eight population-based studies were included with 635,642 total patients. Bariatric surgery was associated with a significant reduction in overall cancer incidence (POR = 0.72; 95% CI 0.59 to 0.87; p = 0.0007) and incidence of obesity-related cancer (POR = 0.55; 95% CI 0.31 to 0.96; p = 0.04). Bariatric surgery was also protective for breast cancer development (POR = 0.50; 95% CI 0.25 to 0.99; p = 0.045). Bariatric surgery appears to be associated with a reduction in cancer incidence at a population-based level.

Leptin signaling and cancer chemoresistance: Perspectives.

Obesity is a major health problem and currently is endemic around the world. Obesity is a risk factor for several different types of cancer, significantly promoting cancer incidence, progression, poor prognosis and resistance to anti-cancer therapies. The study of this resistance is critical as development of chemoresistance is a serious drawback for the successful and effective drug-based treatments of cancer. There is increasing evidence that augmented adiposity can impact on chemotherapeutic treatment of cancer and the development of resistance to these treatments, particularly through one of its signature mediators, the adipokine leptin. Leptin is a pro-inflammatory, pro-angiogenic and pro-tumorigenic adipokine that has been implicated in many cancers promoting processes such as angiogenesis, metastasis, tumorigenesis and survival/resistance to apoptosis. Several possible mechanisms that could potentially be developed by cancer cells to elicit drug resistance have been suggested in the literature. Here, we summarize and discuss the current state of the literature on the role of obesity and leptin on chemoresistance, particularly as it relates to breast and pancreatic cancers. We focus on the role of leptin and its significance in possibly driving these proposed chemoresistance mechanisms, and examine its effects on cancer cell survival signals and expansion of the cancer stem cell sub-populations.

Circulating resistin levels and obesity-related cancer risk: A meta-analysis.

Resistin levels have been reported to be abnormal in obesity-related cancer patients with epidemiological studies yielding inconsistent results. Therefore, a meta-analysis was performed to assess the association between blood resistin levels and obesity-related cancer risk. A total of 13 studies were included for pooling ORs analysis. High resistin levels were found in cancer patients (OR= 1.20, 95% CI= 1.10-1.30). After excluding one study primarily contributing to between-study heterogeneity, the association between resistin levels and cancer risk was still significant (OR=1.18, 95% CI = 1.09-1.28). Stratification analysis found resistin levels were not associated with cancer risk in prospective studies. Meta-regression analysis identified factors such as geographic area, detection assay, or study design as confounders to between-study variance. The result of 18 studies of pooling measures on SMD analysis was that high resistin levels were associated with increased cancer risk (SMD = 0.94, 95% CI = 0.63-1.25), but not in the pooling SMD analysis of prospective studies. Except for the studies identified as major contributors to heterogeneity by Galbraith plot, resistin levels were still higher in cancer patients (SMD = 0.75, 95% CI = 0.63-0.87) in retrospective studies. Meta-regression analysis found factors, such as geographic area, BMI-match, size, and quality score, could account for 66.7% between-study variance in pooling SMD analysis of retrospective studies. Publication bias was not found in pooling ORs analysis. Our findings indicated high resistin levels were associated with increased obesity-related cancer risk. However, it may not be a predictor.