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Simple Summary: The choice between total thyroidectomy and staged completion thyroidectomy for differentiated thyroid cancer remains debated. This study investigated the safety profiles and optimal timing of completion thyroidectomy by analyzing nearly 80,000 patients. The findings demonstrate that total thyroidectomy carries higher risks of temporary and permanent hypoparathyroidism compared to completion thyroidectomy. However, scheduling completion thyroidectomy within 1–6 months of the initial lobectomy can mitigate permanent complication rates. These results provide insights to guide personalized surgical decision-making for thyroid cancer patients. The optimal surgical approach for differentiated thyroid cancer remains controversial, with debate regarding the comparative risks of upfront total thyroidectomy versus staged completion thyroidectomy following the initial lobectomy. This study aimed to assess the complication rates associated with these two strategies and identify the optimal timing for completion thyroidectomy using a multi-dimensional analysis of four cohorts: an institutional series (n = 148), the National Surgical Quality Improvement Program (NSQIP) database (n = 39,992), the TriNetX repository (n > 30,000), and a pooled literature review (10 studies, n = 6015). Institutional data revealed higher overall complication rates with total thyroidectomy (18.3%) compared to completion thyroidectomy (6.8%), primarily due to increased temporary hypocalcemia (10% vs. 0%, p = 0.004). The NSQIP analysis demonstrated that total thyroidectomy was associated with a 72% increased risk of transient hypocalcemia (p < 0.001) and a 25% increased risk of permanent hypocalcemia (p < 0.001). TriNetX data confirmed these findings and identified obesity and concurrent neck dissection as risk factors for complications. A meta-analysis showed that total thyroidectomy increased the rates of transient (RR = 1.63) and permanent (RR = 1.23) hypocalcemia (p < 0.001). Institutional and TriNetX data suggested that performing completion thyroidectomy between 1 and 6 months after the initial lobectomy minimized permanent complication rates compared to delays beyond 6 months. In conclusion, for differentiated thyroid cancer, total thyroidectomy is associated with higher risks of transient and permanent hypocalcemia compared to staged completion thyroidectomy. However, performing completion thyroidectomy within 1–6 months of the initial lobectomy may mitigate the risk of permanent complications. These findings can inform personalized surgical decision-making for patients with differentiated thyroid cancer. [ABSTRACT FROM AUTHOR]

Simple Summary: Colorectal adenoma formation has multiple contributing factors and how these risk factors interact is not precise. Past studies have demonstrated that increased weight is one of the risk factors of colorectal adenoma formation, but does not mean participants with normal body weight are not concerned about colorectal adenoma formation. We aimed to explore the specific risk factors for colorectal adenomas in individuals with normal body weight, who are often overlooked, and the interaction between these risk factors. Background: We aimed to evaluate the interaction between colorectal adenoma risks among asymptomatic individuals in terms of metabolic health status and obesity, and examine the normal waist-to-hip ratio (WHR) in adults with colorectal adenoma risk. Methods: A cross-sectional, retrospective study was conducted at MacKay Memorial Hospital involving 16,996 participants who underwent bidirectional gastrointestinal endoscopy between 2013 and 2023. The study recorded important clinicopathological characteristics, including age, body mass index and WHR, Framingham Risk Score (FRS), blood glucose level, and Helicobacter pylori (H. pylori) infection status. Results: Multivariate logistic regression analysis demonstrated that elevated hemoglobin A1C (HbA1c), increased FRS, positive H. pylori infection, and WHR ≥ 0.9 are independent risk factors for colorectal adenoma. In examining the interaction between FRS and WHR using multivariate logistic regression to evaluate adenoma risk, the OR for the interaction term was 0.95, indicating a decline in adenoma risk when considering the interaction between these two factors. Incorporating HbA1c into the analysis, evaluating the interaction between FRS and WHR still demonstrated a statistically significant impact on adenoma risk (OR 0.96, p < 0.001). Participants with WHR < 0.9, elevated FRS, positive H. pylori infection, and increased HbA1c levels were associated with a higher risk of colorectal adenoma formation. Remarkably, the increased risk of adenoma due to rising HbA1c levels was statistically significant only for those with a WHR < 0.9. Conclusions: An increase in FRS and HbA1c or a positive H. pylori infection still warrants vigilance for colorectal adenoma risk when WHR is 0.9. These factors interacted with each other and were found to have a minimal decline in adenoma risk when considering the interaction between WHR and FRS. [ABSTRACT FROM AUTHOR]

Simple Summary: The rise in worldwide uterine cancer is tied to increasing obesity, influencing substances such as adipocytokines and insulin-like growth factors (IGFs) in the body, promoting cancer mainly through inflammation. Our main objective was to evaluate the levels of adiponectin, leptin, TNFα, IL6, IGFs 1 and 2 in endometrial cancer patients compared to control patients and to examine their relationship with obesity. Additionally, we aimed to explore the correlation between these markers and tumour characteristics. We also conducted a reassessment of the markers 6 months post-surgery to investigate the impact of treatment on these markers. Given the absence of established biomarkers for endometrial cancer, studying these markers and their variations post-surgery may provide valuable prognostic insights. The rising global incidence of uterine cancer is linked to the escalating prevalence of obesity. Obesity results in alterations in adipocytokines and IGFs, driving cancer progression via inflammation, increased cell proliferation, and apoptosis inhibition, although the precise mechanisms are still unclear. This study examined a set of six markers, namely, adiponectin, leptin, IL6, TNFα, IGF1, and IGF2 and compared them between fifty age-matched endometrial cancer patients (study group) and non-cancer patients with benign gynaecological conditions (control group). We also assessed the relationship of these markers with obesity and explored the correlation between these markers and various tumour characteristics. In the cancer population, these markers were also assessed 24 h and 6 months post-surgery. Remarkably, low adiponectin levels were associated with a 35.8% increase in endometrial cancer risk. Interestingly, compared to control subjects where IGF levels decreased after menopause, post-menopausal women in the study group showed elevated IGF1 and IGF2 levels, suggesting a potential influence of endometrial cancer on the IGF system, particularly after menopause. Lastly, it is noteworthy that a discernible inverse relationship trend was observed in the levels of adipocytokines and IGFs 6 months post-surgery. This indicates that treatment for endometrial cancer may have a differential impact on adipocytokines and IGFs, potentially holding clinical significance that merits further investigation. [ABSTRACT FROM AUTHOR]

Simple Summary: Breast cancer is a complex pathology characterized by several features including molecular subtype (MS). Immunohistochemistry assays were used to investigate the expression of enzymes involved in glycolysis and gluconeogenesis. The analysis involved stratifying the data based on MS, body mass index (BMI), and the combination of BMI with MS (mBMI). This study revealed significant differences in the expression of three specific enzymes—pyruvate carboxylase (PC), phosphoenolpyruvate carboxykinase (PCK), and fructose-1,6-bisphosphatase (FBP)—among tumor cells when stratified by MS and mBMI. Moreover, the expression levels of these enzymes were found to be closely related to hormonal receptor and HER2 status, as well as correlated pathological stage and histological grade. Obesity appeared to have an impact on these differences, particularly in the expression of PC. However, it was observed that these differences were not influenced by the presence of adipocyte deposition or inflammatory infiltration within the tumor microenvironment. Nevertheless, the expression of PCK and FBP was also influenced by the presence of obesity-related conditions such as diabetes, hypertension, and dyslipidemia. In summary, this study highlights the existence of distinct metabolic profiles for breast cancer based on its molecular subtypes, and how these profiles are affected by obesity and related health conditions. Breast cancer is a heterogeneous entity, where different molecular subtypes (MS) exhibit distinct prognostic and therapeutic responses. A series of 62 breast cancer samples stratified by MS was obtained from the tumor biobank of IPO-Porto. The expression of glycolysis and gluconeogenesis-regulating enzymes was investigated by immunohistochemistry. Data analysis included stratification according to MS, body mass index (BMI), and BMI with MS (mBMI). We observed significant differences in pyruvate carboxylase (PC), phosphoenolpyruvate carboxykinase (PCK), and fructose-1,6-bisphosphatase (FBP) tumor cell expression when stratified by MS and mBMI. The expression of these enzymes was also statistically dependent on hormonal receptors and HER2 status and correlated with pathological stage and histological grade. Obesity tended to attenuate these differences, particularly in PC expression, although these were not affected by adipocyte deposition or inflammatory infiltration at the tumor microenvironment. Nonetheless, PCK and FBP expression was also modified by the presence of obesity-associated disorders like diabetes, hypertension, and dyslipidemia. Taken together, these findings identify metabolic fingerprints for breast cancer as distinct histological types, which are affected by the presence of obesity and obesity-associated conditions. Despite the biological role of the differential expression of enzymes remaining unknown, the current study highlights the need to identify the expression of gluconeogenic-regulating enzymes as a tool for personalized medicine. [ABSTRACT FROM AUTHOR]

Simple Summary: Gastric cancer is the fifth most prevalent cancer in the world. The relationship between gastric cancer and underweight, overweight, and obesity is not fully understood yet. Obesity is a modifiable factor that has a positive association with some cancers. This systematic review and meta-analysis aimed to investigate the association between gastric cancer risk and abnormal body mass index, as an indicator of abnormal weight. Based on our results, obesity and overweight increase the risk of gastric cancer, while underweight is not associated. These findings can help policymakers and healthcare providers to make preventive strategies for controlling obesity and overweight. This study aimed to investigate the risk of gastric cancer (GC) in abnormal body mass index (BMI) groups. A systematic search was carried out on Embase, PubMed/Medline, and Scopus from January 2000 to January 2023. The pooled risk ratio (RR) with a 95% confidence interval (CI) was assessed using a random-effect model. Thirteen studies with total of 14,020,031 participants were included in this systematic review. The pooled RR of GC was 1.124 (95% CI, 0.968–1.304, I2: 89.08%) in underweight class, 1.155 (95% CI, 1.051–1.270, I2: 95.18%) in overweight class, and in 1.218 (95% CI, 1.070–1.386, I2: 97.65%) obesity class. There is no difference between cardia and non-cardia gastric cancer, while non-Asian race and female gender have higher risk of cancer, as Meta-regression of obesity and overweight classes showed. These findings suggest that there is a positive association between excess body weight and the risk of GC, with a higher impact in women than men and in non-Asian than Asian populations. Since abnormal weight is tied to various diseases, including GC, healthcare experts, and policymakers should continue interventions aiming to achieve a normal BMI range. [ABSTRACT FROM AUTHOR]

Simple Summary: The impact of obesity on melanoma has rarely been researched. Incidence of obesity is rapidly growing and melanoma is one of the most prevalent types of cancers worldwide. Several studies have shown that overweight and obese populations not only have a higher risk of developing melanoma but also tend to present with thicker melanomas at the time of diagnosis. Given that melanoma thickness is one of the main predictors of the melanoma prognosis, a worse prognosis in a patient with obesity would be expectable. However, this has not yet been demonstrated in the literature. Our study is the first to show that obese patients are twice more likely to present with lymph-node metastases. Lymph node metastases is the second most important prognosis predictor of melanoma. Our findings, therefore, raise important questions regarding the screening and treatment of obese patients with melanoma. (1) Background: While obesity is a known independent risk factor in the development of melanoma, there is no consensus on its influence on melanoma prognosis. (2) Methods: In a monocentric retrospective study, data was collected from patients who underwent sentinel lymph node (SLN) biopsy for stage IB-IIC melanoma between 2013 and 2018. Patients were divided into groups according to their body mass index (BMI). The association between BMI and melanoma features, as well as the risk factors for metastases in SLN were examined. (3) Results: Of the 1001 patients, 336 had normal weight (BMI < 25), 402 were overweight (BMI >= 25 and <30), 173 obese (BMI >= 30 and <35) and 90 extremely obese (BMI >= 35). Overweightness and obesity were associated with higher tumor thicknesses at time of diagnosis. Ulceration was not influenced by the patient's weight. Metastases in sentinel lymph node was almost twice more likely in extremely obese patients than in normal weight patients. Independent risk factors for metastases in SLN in our study were tumor thickness, ulceration, and BMI > 35. (4) Conclusions: This is the first study to show higher metastases rates in high-BMI patients with melanoma, raising important questions regarding the screening and treatment of this specific patient population. [ABSTRACT FROM AUTHOR]

Simple Summary: Concomitant hepatic steatosis is common in patients with chronic hepatitis B (CHB), but data regarding its impact on the natural history of CHB remain sparse and conflicting. Recently, metabolic-associated fatty liver disease (MAFLD) was defined as hepatic steatosis in the presence of metabolic abnormality. The utility of MAFLD and its ability to assess hepatocellular carcinoma (HCC) risk for CHB requires further investigation. In this population-based cohort study of CHB, MAFLD was not associated with an increased risk of HCC. However, it was associated with a higher probability of functional cure for CHB in terms of HBsAg loss, and the MAFLD–HCC association was largely mediated by the development of HBsAg seroclearance driven by hepatic steatosis. On the contrary, the burden of metabolic risk abnormality was robustly associated with an increased risk of HCC in CHB, and this association was observed for participants both with and without hepatic steatosis and for participants both with and without HBsAg seroclearance. The value of metabolic-associated fatty liver disease (MAFLD) and its ability to assess hepatocellular carcinoma (HCC) risk remains uncertain for chronic hepatitis B (CHB). We evaluated the impacts of MAFLD and its coincidental metabolic abnormalities and related genetic predisposition on HCC incidence and mortality outcomes in CHB. We analyzed data from 1453 HBsAg-positive men (median age = 49.2 years at baseline) from a cohort of civil servants recruited from 1989–1992. MAFLD was defined as hepatic steatosis on ultrasound with obesity, diabetes, or metabolic dysfunction at baseline. During follow-up (median = 19.3 years), 105 HCC events occurred. MAFLD was not associated with HCC (adjusted hazard ratio (aHR) = 1.02) but was associated with a higher HBsAg seroclearance rate (aHR = 1.43). In mediation analysis, HBsAg seroclearance driven by hepatic steatosis explained 31.6% of the association between MAFLD and HCC. Antiviral treatment or fatty liver disease-associated genetic variants did not influence the MAFLD–HCC association. In contrast, even after adjustment for MAFLD and the other metabolic abnormalities, diabetes (aHR = 2.28), obesity (aHR = 1.72), and metabolic dysfunction (aHR = 3.30) increased the risk of HCC (all p < 0.030). The risk of HCC increased with the number of metabolic abnormalities (vs 0: aHR = 2.05 and 5.72 for 2 and ≥ 3 metabolic abnormalities, respectively), and the cumulative effect of metabolic abnormalities was found across subgroups categorized by hepatic steatosis as well as in participants both with and without HBsAg seroclearance. In conclusion, MAFLD was not associated with increased HCC incidence in CHB. A more informative assessment of HCC risk can be obtained by taking into account the number of metabolic abnormalities. [ABSTRACT FROM AUTHOR]

Simple Summary: Regarding the association between obesity and thyroid cancer, most previous studies have focused only on body mass index (BMI), but other measures of obesity have not been studied much with inconsistent results. This study showed a significant association between increased abdominal obesity indexes, such as waist circumference (WC, ≥85.0 cm) and waist-height ratio (WHTR ≥ 0.5) as well as BMI (≥25.0 Kg/m2), and increased risk of thyroid cancer. In addition, people who had both abnormally obese levels of BMI and other obesity indexes including WC, waist–hip ratio, or WHTR showed an increased risk of thyroid cancer, compared to those with normal levels of BMI and each obesity index. These results provide evidence of the contribution of both total and central adiposity across the lifespan to thyroid cancer incidence. Risk factor modifications must be considered to explain the current thyroid cancer epidemic. Objective: This study aimed to identify the association between various obesity indexes, including waist circumference (WC), waist–hip ratio (WHR), waist–height ratio (WHTR), and BMI, and their combinations with body mass index (BMI) and thyroid cancer risk. Methods: Of the 65,639 participants who completed a follow-up survey of the Health Examinee Study (HEXA), a prospective cohort of the Korean Genome and Epidemiology Study, 412 female incident thyroid cancer cases, and 1648 birth year- and enrollment year-matched female controls were included. Multiple conditional logistic regression was used to estimate the association between obesity indexes and thyroid cancer risk. Results: The risk of developing thyroid cancer was increased by 1.37-fold (95% confidence interval (CI) = 1.03–1.81) higher in the obese BMI group (≥25.0 Kg/m2) compared to that in the normal BMI group (<23.0 Kg/m2). Obesity in terms of WC (≥85.0 cm) and WHTR (≥0.5) was associated with an increased risk of thyroid cancer (OR 1.55, 95% CI = 1.16–2.07; OR 1.37, 95% CI = 1.07–1.75, respectively). However, increased WHR levels did not show any significant association. Women with both obese levels of BMI (≥25.0 Kg/m2) and other obesity indexes (WC ≥ 85.0 cm, WHR ≥ 0.85, or WHTR ≥ 0.5) showed an increased risk of thyroid cancer with OR of 1.63 (95% CI = 1.14–2.31), 1.49 (95% CI = 1.05–2.12), and 1.42 (95% CI = 1.04–1.94), compared to those with normal levels of BMI and each obesity index. Conclusion: These results provide evidence of the contribution of both total and central adiposity across the lifespan of thyroid cancer incidence. Risk factor modifications must be considered to explain the current thyroid cancer epidemic. [ABSTRACT FROM AUTHOR]

Simple Summary: Our study evaluated the risk factors of incident lung cancer in subjects with newly diagnosed bronchiectasis, using a large nationwide database. In this study, we showed that male sex, overweight, current smoking, living in rural areas, and comorbid COPD were independently associated with a higher risk of incident lung cancer in participants with bronchiectasis, while mild alcohol consumption was negatively associated with lung cancer development in those with bronchiectasis. To our knowledge, this is the first study assessing the risk factors of lung cancer in patients with bronchiectasis, and it would be helpful for clinicians at real practice. Background: Patients with non-cystic fibrosis bronchiectasis have an increased risk of lung cancer, followed by higher mortality in this population. Because the risk factors of lung cancer have not been well identified, this study aimed to investigate the risk factors of lung cancer in individuals with newly diagnosed bronchiectasis. Methods: This cohort study using the Korean National Health Insurance Service database identified 7425 individuals with incident bronchiectasis among those who participated in the health screening exam in 2009. The cohort was followed from baseline to the date of incident: lung cancer, death, or until the end of the study period. We investigated the risk factors of lung cancer in participants with bronchiectasis using the Cox–proportional hazard models. Results: During median 8.3 years of follow-up duration, 1.9% (138/7425) developed lung cancer. In multivariable analyses, significant factors associated with increased risk of incident lung cancer included: males (adjusted hazard ratio [HR] = 3.54, 95% confidence interval [CI] = 2.17–5.79) than females, the overweight (adjusted HR = 1.55, 95% CI = 1.03–2.35) than the normal weight, current smokers (adjusted HR = 3.10, 95% CI = 2.00–4.79) than never smokers, participants living in the rural area (adjusted HR = 2.54, 95% CI = 1.68–3.85) than those living in the metropolitan area. Among comorbidities, chronic obstructive pulmonary disease was associated with an increased risk of lung cancer (adjusted HR = 1.46, 95% CI = 1.01–2.13) in participants with bronchiectasis. In contrast, mild alcohol consumption was associated with reduced risk of lung cancer (adjusted HR = 0.47, 95% CI = 0.29–0.74) in those with bronchiectasis. Conclusion: This Korean population-based study showed that males, current smoking, overweight, living in rural areas, and comorbid chronic obstructive pulmonary disease are associated with increased risk of lung cancer in individuals with bronchiectasis. [ABSTRACT FROM AUTHOR]

Simple Summary: By analyzing a large German primary care provider database, we demonstrated that obesity represents a decisive risk factor for the development of colon, rectal, and liver cancer, partly in a sex-dependent manner. Thus, along with previous data, our study including >280,000 patients suggests that the clinical management of overweight patients should include a careful and structured risk assessment for the development of cancer in order to improve long-term outcomes in these patients. Cancer represents the second leading cause of death worldwide, implementing a major health care and socioeconomic burden. Overweight and obesity, both of which are dramatically on the rise in both highly and less developed regions worldwide, have been established as modifiable risk factors for the development of various tumor entities including gastrointestinal (GI) cancers such as colorectal or gastric cancer. However, systematic data on an association between excessive body fat and GI cancer development from Germany are missing. Methods: A total of 287,357 adult outpatients with an available BMI value between 2010 and 2019 were identified from the Disease Analyzer database (IQVIA). The main outcome was the association between pre-obesity (BMI 25–30 kg/m2) and obesity (BMI ≥ 30 kg/m2) compared to normal weight (BMI 18.5–25 kg/m2) and the incident of a GI cancer diagnoses (including colon, rectum, stomach, pancreas, and liver cancer). Results: Within the observation period, the proportion of colon cancer patients increased stepwise from 0.5% and 0.64% in normal weight to 0.71% and 0.91% in obese female and male patients, respectively, which was confirmed in multivariable regression models (ORfemale obesity: 1.23; 95% CI: 1.03–1.48; ORmale obesity: 1.43, 95% CI: 1.17–1.74). In contrast, multivariable regression models revealed that obesity was significantly associated with rectal cancer (OR: 1.36, 95% CI: 1.01–1.84) as well as liver cancer (OR: 1.79, 95% CI: 1.17–2.73) in men only. Conclusions: Our data suggest that obesity represents a decisive risk factor for the development of colon, rectal, and liver cancer, partly in a sex-dependent manner. Since overweight and obesity are modifiable risk factors, the current results may help to establish appropriate prevention and lifestyle programs to reduce both the incidence as well as the high morbidity and mortality of GI tumors in the future. [ABSTRACT FROM AUTHOR]

Simple Summary: Oesophagogastric adenocarcinomas (OAC) are cancers of the food pipe and stomach which have a strong link with obesity. Natural killer (NK) cells are assassins of the immune system and are crucial for eliminating cancer. We have shown previously that NK cells are pulled into fat in OAC patients by a signalling protein called fractalkine (CX3CL1). Once in fat, NK cells die or are profoundly altered. This diminishes their ability to kill the tumour. We report that exposure to fat can reduce movement of NK cells towards the tumour. However, if a drug called a CX3CR1 antagonist is used to antagonise the receptor for fractalkine, we can restore NK cell movement towards the tumour. When we activate NK cells with a protein called IL-15, fractalkine can reduce its effect on NK cells. This provides further evidence for using CX3CR1 antagonists to reduce NK cell migration to fat and boost NK cell movement to the tumour. Oesophagogastric adenocarcinomas (OAC) are obesity-associated malignancies, underpinned by severe immune dysregulation. We have previously shown that natural killer (NK) cells preferentially migrate to OAC omentum, where they undergo phenotypic and functional alterations and apoptosis. Furthermore, we have identified the CX3CR1:fractalkine (CX3CL1) pathway as pivotal in their recruitment to omentum. Here, we elucidate whether exposure to the soluble microenvironment of OAC omentum, and in particular fractalkine and IL-15 affects NK cell homing capacity towards oesophageal tumour. Our data uncover diminished NK cell migration towards OAC tumour tissue conditioned media (TCM) following exposure to omental adipose tissue conditioned media (ACM) and reveal that this migration can be rescued with CX3CR1 antagonist E6130. Furthermore, we show that fractalkine has opposing effects on NK cell migration towards TCM, when used alone or in combination with IL-15 and uncover its inhibitory effects on IL-15-mediated stimulation of death receptor ligand expression. Interestingly, treatment with fractalkine and/or IL-15 do not significantly affect NK cell adhesion to MAdCAM-1, despite changes they elicit to the expression of integrin α4β7. This study provides further evidence that CX3CR1 antagonism has therapeutic utility in rescuing NK cells from the deleterious effects of the omentum and fractalkine in OAC, thus limiting their dysfunction. [ABSTRACT FROM AUTHOR]

Simple Summary: The causal impact of body fat distribution on female-specific cancers is largely unknown. For the first time we used a two-sample multivariable Mendelian randomization (MR) approach to elucidate the role and causal relations of body composition assessed by segmental bioelectrical impedance analysis on the risks of breast, endometrial and ovarian cancers and their subtypes. We found that abdominal fat content increases the risk for ovarian cancer and its endometrioid and clear cell subtypes independent of overall fat content. General adiposity has a protective effect on risk of breast cancer and its ER- and ER+ subtypes but increases the risk for endometrial cancer, ovarian cancer, and the endometrioid ovarian cancer subtype. This study extends the literature by addressing specifically the causal role of visceral fat on female-specific cancers. Background: Mounting evidence shows that adiposity increases female-specific cancer risk, but the role of body fat distribution is less clear. We used a two-sample Mendelian randomization (MR) approach to elucidate causal relations of body fat distribution to the risks of breast, endometrial and ovarian cancers and their subtypes. Methods: Body composition was assessed using segmental bioelectrical impedance analysis, yielding trunk, arm, and leg fat ratios (TFR, AFR, LFR) and BMI including 195,043 and 434,794 European women, respectively. The sample sizes for the outcomes ranged between 58,396 and 228,951. Causal effects were estimated per one standard deviation increment in the respective exposure within the radial regression framework. Robust sensitivity analyses were performed to verify MR assumptions. In a multivariable MR setting, the proportion of risk attributable to overall and abdominal fat content was assessed. Results: TFR, which represents abdominal fat content, was associated with ovarian cancer and its clear cell and endometrioid histotypes independent of overall fat content. BMI was inversely associated with breast cancer and its ER− and ER+ subtypes, but positively with endometrial cancer and ovarian cancer, including its endometrioid histotype. These estimates were confirmed using AFR as proxy for overall body fat. Conclusions: Visceral adiposity seems to be a driver of elevated ovarian cancer risk, particularly of the endometrioid and clear cell ovarian cancer histotypes. General adiposity decreases the risk of breast cancer but increases the risk of endometrial and ovarian cancer. [ABSTRACT FROM AUTHOR]

Simple Summary: Obese breast cancer patients have an increased risk for metastasis; however, the mechanisms are not well characterized. Here, we show that obesity promotes rapid mammary tumor growth and enhances metastases in mice. Within the lungs of non-tumor-bearing mice, obesity increased recruitment of myeloid lineage cells and elevated deposition of collagen fibers. Lung stromal cells isolated from obese mice demonstrated increased expression of extracellular matrix proteins and inflammatory cytokines, including colony-stimulating factor 2 (CSF2). Conditioned media from lung stromal cells of obese mice promoted the invasion of myeloid lineage cells, which was dependent upon lung stromal cell expression of CSF2. These studies suggest that obesity creates an environment conducive to metastatic growth in the lungs prior to tumor formation. Understanding how obesity promotes metastases may increase therapeutic options for a growing population of obese breast cancer patients. Obesity is correlated with increased incidence of breast cancer metastasis; however, the mechanisms underlying how obesity promotes metastasis are unclear. In a diet-induced obese mouse model, obesity enhanced lung metastasis in both the presence and absence of primary mammary tumors and increased recruitment of myeloid lineage cells into the lungs. In the absence of tumors, obese mice demonstrated increased numbers of myeloid lineage cells and elevated collagen fibers within the lung stroma, reminiscent of premetastatic niches formed by primary tumors. Lung stromal cells isolated from obese tumor-naïve mice showed increased proliferation, contractility, and expression of extracellular matrix, inflammatory markers and transforming growth factor beta-1 (TGFβ1). Conditioned media from lung stromal cells from obese mice promoted myeloid lineage cell migration in vitro in response to colony-stimulating factor 2 (CSF2) expression and enhanced invasion of tumor cells. Together, these results suggest that prior to tumor formation, obesity alters the lung microenvironment, creating niches conducive to metastatic growth. [ABSTRACT FROM AUTHOR]

Among 29,701 Black and White participants aged 45 years and older in the Reasons for Geographic and Racial Difference in Stroke (REGARDS) study, allostatic load (AL) was defined as the sum score of established baseline risk-associated biomarkers for which participants exceeded a set cutoff point. Cox proportional hazard regression was utilized to determine the association of AL score with all-cause and cancer-specific mortality, with analyses stratified by body-mass index, age group, and race. At baseline, Blacks had a higher AL score compared with Whites (Black mean AL score: 2.42, SD: 1.50; White mean AL score: 1.99, SD: 1.39; p < 0.001). Over the follow-up period, there were 4622 all-cause and 1237 cancer-specific deaths observed. Every unit increase in baseline AL score was associated with a 24% higher risk of all-cause (HR: 1.24, 95% CI: 1.22, 1.27) and a 7% higher risk of cancer-specific mortality (HR: 1.07, 95% CI: 1.03, 1.12). The association of AL with overall- and cancer-specific mortality was similar among Blacks and Whites and across age-groups, however the risk of cancer-specific mortality was higher among normal BMI than overweight or obese participants. In conclusion, a higher baseline AL score was associated with increased risk of all-cause and cancer-specific mortality among both Black and White participants. Targeted interventions to patient groups with higher AL scores, regardless of race, may be beneficial as a strategy to reduce all-cause and cancer-specific mortality. [ABSTRACT FROM AUTHOR]