Estrogen Plus Progestin and Colorectal Cancer: Long-Term Findings From the Women's Health Initiative Randomized Clinical Trial.

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.We report long-term colorectal cancer findings from the Women's Health Initiative trial where 16,608 postmenopausal women with a uterus were randomly assigned to daily conjugated equine estrogen (CEE) 0.625 mg, plus medroxyprogesterone acetate (MPA) 2.5 mg, or placebo. When intervention ended after 5.6 years, although there were 44% fewer colorectal cancers in the intervention group (43 v 72, P = .003), the cancers were more commonly lymph node-positive (59.0% v 29.4%, P = .003). Now after cumulative 24-year follow-up, with 431 colorectal cancers, CEE plus MPA no longer influenced colorectal cancer incidence (215 [0.15, annualized rate %] v 216 [0.15], hazard ratio [HR], 0.95 [95% CI, 0.79 to 1.15]). Although not statistically significant, there were more colorectal cancer deaths with CEE plus MPA (87 [0.049] v 69 [0.041] deaths, HR, 1.20 [95% CI, 0.87 to 1.65], P = .26). Vaginal bleeding (54.1% v 5.2% at 6 months) and breast changes were more frequent in the intervention group. After adjusting for postrandomization vaginal bleeding and breast changes, bowel examinations were significantly delayed in intervention group participants (P = .005), potentially contributing to diagnostic delay. Taken together, the findings suggest no clinically meaningful benefit for about 5 years of CEE plus MPA use on colorectal cancer outcome.

Prospective longitudinal relations among frequent social media use, nicotine vaping and experiencing internalizing mental health problems.

AIMS: To compare four a priori rival mediated pathways of frequent social media use, electronic nicotine delivery systems (ENDS) use and internalizing mental health (MH) problems across five waves of nationally representative data. DESIGN, SETTING AND PARTICIPANTS: This was a longitudinal study using data drawn from waves 2-5 (October 2014-November 2019) of the Population Assessment of Tobacco and Health Study, a nationally representative cohort study spanning approximately 5 years, conducted in the United States. The analytical sample of participants included those who were aged 12-14 years at wave 2 and who provided data in subsequent waves until wave 4.5 (n = 4627, 69.7% were White and 51.4% were male). MEASUREMENTS: Frequent social media use (several times a day), ENDS use (past 30-day use) and internalizing MH problems (endorsed symptoms on four items in the past year) were dichotomized for analysis. FINDINGS: The weighted proportions of the three key variables increased over time. From wave 2 to wave 5, frequent social media use grew from 56.9 to 77.2%; internalizing MH problems from 18.9 to 29.0%; and ENDS use from 1.4 to 11.4%. In weighted logistic regressions using generalized linear mixed models with random effects, there was a significant within-person association between frequent social media use at time t and greater ENDS use at t + 1 [adjusted odds ratio (aOR) = 1.87; 95% confidence interval (CI) = 1.47, 2.37] and worsened internalizing MH problems at t + 1 (aOR = 1.19; 95% CI = 1.04, 1.37). A model-based causal mediation analysis and marginal structural models were fitted to estimate the average causal mediation effect. Among all four examined mediation pathways throughout the three constructs, partial mediation was observed, and all the pathways were significant for both boys and girls. Sex differences did not emerge in the examined prospective mediated pathways. CONCLUSIONS: Among youth in the United States, frequent social media use appears to mediate the prospective association between experiencing internalizing mental health problems and using electronic nicotine delivery systems.

Spatiotemporal heterogeneity of lake carbon dioxide flux leads to substantial uncertainties in regional upscaling estimates.

Limited field samplings result in significant uncertainties in regional and global estimates of lake carbon dioxide (CO2) emissions. However, quantitative analysis of uncertainty in regional lake CO2 emission estimates remains unclear. In this study, we utilized satellite data to estimate carbon dioxide flux from 113 eastern China lakes, revealing substantial spatial and temporal variations in flux, averaging 18.07 ±â€¯81.83 mg m-2 d-1. Additionally, satellite-estimated total CO2 effluxes indicated previous upscaling studies had overestimated total CO2 effluxes from these studied lakes by approximately 3-11 times, primarily due to substantial variations in lake CO2 fluxes. Insufficient sampling resolution resulted in considerable uncertainty in upscaling estimations. Temporal variations in carbon dioxide contributed greater upscaling uncertainties than spatial variations in carbon dioxide. To capture the dynamics of lake CO2, increasing the number of sampling points and events is necessary as lake size decreases and trophic state increases. Finally, we propose a prediction for the optimal sampling resolution based on lake area and trophic state, recommending an average of 5 points per lake and bi-monthly sampling as the ideal resolution for similar shallow eutrophic lakes. This approach has been validated as effective in lakes across North America and Europe. We believe that future global-scale lake carbon budget estimates would benefit from field observations conducted at more reasonable sampling points and frequency.

Use of non-steroidal anti-inflammatory drugs and pancreatic cancer risk in the Women's Health Initiative.

BACKGROUND: Pancreatic cancer is among the most fatal human cancers and the fourth leading cause of cancer death in the United States. Evidence suggests that chronic inflammation may play a role in pancreatic carcinogenesis, and its inhibition through non-steroidal anti-inflammatory drugs (NSAIDs) may reduce pancreatic cancer incidence. METHODS: We examined associations of total and individual NSAIDs with pancreatic cancer risk among postmenopausal women participating in the Women's Health Initiative observational study and clinical trials cohorts. Among 117,452 women, ages 55-79 years, 727 incident pancreatic cancer cases were reported over 18 years of follow-up. Cox regression was used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for associations between NSAIDs and pancreatic cancer risk. RESULTS: Relative to non-use, consistent use of any NSAID was inversely associated with pancreatic cancer risk (HR 0.71, 95% CI: 0.59-0.87), primarily driven by strong associations for aspirin use (HR 0.67, 95% CI: 0.52-0.86). Use of total or individual non-aspirin NSAIDs were not associated with pancreatic cancer. Upon stratified analysis, we observed stronger associations for NSAIDs among participants with prevalent diabetes (HR 0.28, 95% CI: 0.10-0.75) relative to those without (HR 0.75, 95% CI: 0.61-0.92; P-interaction=0.03). CONCLUSIONS: Additional large prospective studies with careful measurement of NSAID type, dose, and frequency are needed to further investigate the possibility of added benefit among individuals diagnosed with diabetes. IMPACT: This study adds to existing evidence from prospective studies and clinical trials suggesting that use of aspirin may provide moderate benefit for pancreatic cancer prevention.

Association of tea and coffee consumption and biliary tract cancer risk: The Biliary Tract Cancers Pooling Project.

BACKGROUND AND AIMS: Tea and coffee are widely consumed beverages worldwide. We evaluated their association with biliary tract cancer (BTC) incidence. APPROACH AND RESULTS: We pooled data from 15 studies in the Biliary Tract Cancers Pooling Project to evaluate associations between tea and coffee consumption and biliary tract cancer development. We categorized participants as nondrinkers (0 cup/day), moderate drinkers (>0 and <3 cups/day), and heavy drinkers (≥3 cups/day). We estimated multivariable HRs and 95% CIs using Cox models. During 29,911,744 person-years of follow-up, 851 gallbladder, 588 intrahepatic bile duct, 753 extrahepatic bile duct, and 458 ampulla of Vater cancer cases were diagnosed. Individuals who drank tea showed a statistically significantly lower incidence rate of gallbladder cancer (GBC) relative to tea nondrinkers (HR=0.77; 95% CI, 0.64-0.91), and intrahepatic bile duct cancer (IHBDC) had an inverse association (HR=0.81; 95% CI, 0.66-1.00). However, no associations were observed for extrahepatic bile duct cancer (EHBDC) or ampulla of Vater cancer (AVC). In contrast, coffee consumption was positively associated with GBC, with a higher incidence rate for individuals consuming more coffee (HR<3 cups/day =1.29; 95% CI, 1.01-1.66; HR≥3 cups/day =1.49; 95% CI, 1.11-1.99, Ptrend=0.01) relative to coffee nondrinkers. However, there was no association between coffee consumption and GBC when restricted to coffee drinkers. There was little evidence of associations between coffee consumption and other biliary tract cancers. CONCLUSIONS: Tea consumption was associated with a lower incidence of GBC and possibly IHBDC. Further research is warranted to replicate the observed positive association between coffee and GBC.

Coordinated dynamics of aquaculture ponds and water eutrophication owing to policy: A case of Jiangsu province, China.

Aquaculture ponds (APs) are rapidly expanding globally and are considered crucial for guaranteeing the supply of food, population growth, and economic development. However, the rapid expansion of aquaculture not only brought benefits but also a series of eco-environmental issues, such as water eutrophication. To achieve sustainable development, it is essential to gain a profound understanding of the spatiotemporal evolution of APs, the drivers behind their dynamics, and their relationship with the aquatic environment. Jiangsu Province (JS) in China, a historically significant aquaculture region, encompasses two prominent river basins: the Huai River Basin (HRB) and the Yangtze River Basin (YRB). In light of the construction of an ecological civilization, JS serves as a demonstration and pioneering area for basin protection and development. Therefore, this study focuses on JS, aiming to elucidate the spatiotemporal dynamics of APs, the corresponding relationship with basin management policies, and the impact on water eutrophication. The results revealed that: (1) in 2022, APs in JS were unevenly distributed, with a total area of 3278.78 km2, of which 79 % was located in the HRB. (2) During 2016-2022, APs exhibited an initial growth trend before 2019, followed by a decrease. (3) Due to policy interventions, AP changes within different basins showed opposite trends, and the corresponding water eutrophic state aligned with AP dynamics. The findings of this study can serve as a typical case to provide scientific evidence for the formulation and implementation of policies to improve the water environment in eutrophic basins.

Low physical function following cancer diagnosis is associated with higher mortality risk in postmenopausal women.

BACKGROUND: Postmenopausal women with cancer experience an accelerated physical dysfunction beyond what is expected through aging alone due to cancer and its treatments. The aim of this study was to determine whether declines in physical function after cancer diagnosis are associated with all-cause mortality and cancer-specific mortality. METHODS: This prospective cohort study included 8068 postmenopausal women enrolled in the Women's Health Initiative with a cancer diagnosis and who had physical function assessed within 1 year of that diagnosis. Self-reported physical function was measured using the 10-item physical function subscale of the 36-Item Short Form Health Survey. Cause of death was determined by medical record review, with central adjudication and linkage to the National Death Index. Death was adjudicated through February 2022. RESULTS: Over a median follow-up of 7.7 years from cancer diagnosis, 3316 (41.1%) women died. Our results showed that for every 10% difference in the physical function score after cancer diagnosis versus pre-diagnosis, all-cause mortality and cancer-specific mortality were reduced by 12% (hazard ratio [HR] = 0.88, 95% confidence interval [95% CI] = 0.87 to 0.89 and HR = 0.88, 95% CI = 0.86 to 0.91, respectively). Further categorical analyses showed a significant dose-response relationship between postdiagnosis physical function categories and mortality outcomes (P < .001 for trend), where the median survival time for women in the lowest physical function quartile was 9.1 years (Interquartile range [IQR] = 8.6-10.6 years) compared with 18.4 years (IQR = 15.8-22.0 years) for women in the highest physical function quartile. CONCLUSION: Postmenopausal women with low physical function after cancer diagnosis may be at higher risk of mortality from all causes and cancer-related mortality.

Vegetarian diets and risk of nonalcoholic fatty liver disease: An observational study of National Health and Nutrition Examination Survey 2005-2018 using propensity score methods.

BACKGROUND: Studies on the association between vegetarian diets and nonalcoholic fatty liver disease (NAFLD) are limited and have inconsistent results. This study aims to explore the association between vegetarian diets and NAFLD and compare the stage of fibrosis between vegetarians and nonvegetarians in a US representative sample. METHODS: Cross-sectional data from 23,130 participants aged ≥20 years were obtained from the National Health and Nutrition Examination Survey, 2005-2018. Vegetarian status was classified based on two 24-h dietary recalls. We examined the association between vegetarian diets and the risk of NAFLD using the propensity score weighting method. RESULTS: Vegetarian diets were significantly associated with decreases in hepatic steatosis index (HSI), US fatty liver index and nonalcoholic fatty liver disease fibrosis score with mean differences of -2.70 (95% confidence interval [CI]: -3.69, -1.70), -3.03 (95% CI: -7.15, -0.91) and -0.12 (95% CI: -0.26, -0.01), respectively. While modelling the risk of NAFLD, we estimated that vegetarians were 53% less likely to have NAFLD assessed by HSI (odds ratios [OR]: 0.47; 95% CI: 0.34, 0.65). The effect of vegetarian diets was higher among individuals with lower waist circumferences (OR: 0.20) than among those with higher waist circumferences (OR: 0.53, p interaction ${p}_{\text{interaction}}\,$ = 0.004). However, the association was largely attenuated after adjusting for body mass index and diabetes status. No significant association was identified between vegetarian diets and advanced fibrosis. CONCLUSIONS: Vegetarian diets were associated with a lower prevalence of NAFLD among US adults, and the association appeared to be stronger in people with lower waist circumferences. Further studies are warranted to replicate our findings.

SGLT2 Inhibitor Use and Risk of Breast Cancer Among Adult Women with Type 2 Diabetes.

INTRODUCTION: Sodium-glucose cotransporter 2 (SGLT2) inhibitors are a relatively new class of antihyperglycemic agents, with the potential to inhibit breast cancer development. However, the association between SGLT2 inhibitors and risk of breast cancer in human studies is unclear. OBJECTIVE: The aim of our study is to use a large national claims database to assess the association between SGLT2 inhibitor use and risk of breast cancer. METHODS: We considered a study population of 158,483 adult women with type 2 diabetes who newly initiated SGLT2 inhibitors or dipeptidyl peptidase 4 (DPP4) inhibitors using Optum's deidentified Clinformatics Data Mart Database between 1 January 2013 and 31 March 2022. The association between SGLT2 inhibitor use and risk of breast cancer was examined using Cox proportional hazard models stratified by age in the overall sample and in a subsample based on propensity score and medication initiation time matching. The effect of medication use duration was explored. RESULTS: With an average follow-up of 2.2 years, 2154 breast cancer cases were identified. There was no significant association between SGLT2 inhibitor use and the risk of breast cancer in overall sample (HR = 0.96; 95% CI 0.87, 1.06), in women younger than 51 years old (HR = 0.88; 95% CI 0.59, 1.32), or in women aged 51 years or older (HR = 0.95; 95% CI 0.86, 1.04). The results remained nonsignificant using matching, medication use duration, and sensitivity analyses. CONCLUSION: Our findings suggest SGLT2 inhibitors use was not associated with breast cancer risk compared with DPP4 inhibitors use. Studies with longer follow-up and better adjustments are needed to confirm the finding.

A novel strategy for estimating biomass of submerged aquatic vegetation in lake integrating UAV and Sentinel data.

Submerged aquatic vegetation (SAV) plays a fundamental ecological role in mediating carbon cycling within lakes, and its biomass is essential to assess the carbon sequestration potential of lake ecosystems. Remote sensing (RS) offers a powerful tool for large-scale SAV biomass retrieval. Given the underwater location of SAV, the spectral signal in RS data often exhibits weakness, capturing primarily horizontal structure rather than volumetric information crucial for biomass assessment. Fortunately, easily-measured SAV coverage can serve as an intermediary variable for difficultly-quantified SAV biomass inversion. Nevertheless, obtaining enough SAV coverage samples matching satellite image pixels for robust model development remains problematic. To overcome this challenge, we employed a UAV to acquire high-precision data, thereby replacing manual SAV coverage sample collection. In this study, we proposed an innovative strategy integrating unmanned aerial vehicle (UAV) and satellite data to invert large-scale SAV coverage, and subsequently estimate the biomass of the dominant SAV population (Potamogeton pectinatus) in Ulansuhai Lake. Firstly, a coverage-biomass model (R2 = 0.93, RMSE = 0.8 kg/m2) depicting the relationship between SAV coverage and biomass was developed. Secondly, in a designed experimental area, a high-precision multispectral image was captured by a UAV. Based on the Normalized Difference Water Index (NDWI), the UAV-based image was classified into non-vegetated and vegetated areas, thereby generating an SAV distribution map. Leveraging spatial correspondence between satellite pixels and the UAV-based SAV distribution map, the proportion of SAV within each satellite pixel, referred to as SAV coverage, was computed, and a coverage sample set matched with satellite pixels was obtained. Subsequently, based on the sample set, a satellite-scale SAV coverage estimation model (R2 = 0.78, RMSE = 14.05 %) was constructed with features from Sentinel-1 and Sentinel-2 data by XGBoost algorithm. Finally, integrating the coverage-biomass model with the obtained coverage inversion results, fresh biomass of SAV in Ulansuhai Lake was successfully estimated to be approximately 574,600 tons.

Hysterectomy, oophorectomy and risk of non-Hodgkin's lymphoma.

Hysterectomy is associated with an increased risk for adverse health outcomes. However, its connection to the risk of non-Hodgkin's lymphoma (NHL) remains unclear. The aims of our study were to investigate the associations between hysterectomy, oophorectomy and risk of NHL and its major subtypes (eg, diffuse large B-cell lymphoma [DLBCL]), and whether these associations were modified by exogenous hormone use. Postmenopausal women (n = 141,621) aged 50-79 years at enrollment (1993-1998) from the Women's Health Initiative were followed for an average of 17.2 years. Hysterectomy and oophorectomy were self-reported at baseline. Incident NHL cases were confirmed by central review of medical records and pathology reports. During the follow-up period, a total of 1719 women were diagnosed with NHL. Hysterectomy, regardless of oophorectomy status, was associated with an increased risk of NHL (hazard ratio [HR] = 1.23, 95% confidence interval [CI]: 1.05-1.44). Oophorectomy was not independently associated with NHL risk after adjusting for hysterectomy. When stratified by hormone use, the association between hysterectomy and NHL risk was confined to women who had never used hormone therapy (HR = 1.35, 95% CI: 1.06-1.71), especially for DLBCL subtype (P for interaction = .01), and to those who had undergone hysterectomy before the age of 55. Our large prospective study showed that hysterectomy was a risk factor of NHL. Findings varied by hormone use. Future studies incorporating detailed information on the types and indications of hysterectomy may deepen our understanding of the mechanisms underlying DLBCL development and its potential interactions with hormone use.

Allostatic load and risk of invasive breast cancer among postmenopausal women in the U.S.

OBJECTIVE: Allostatic load can reflect the body's response to chronic stress. However, little is known about the association between allostatic load and risk of breast cancer in postmenopausal women. This study used a large prospective cohort in the United States to examine the relationship between allostatic load and invasive breast cancer risk, and to evaluate the relationship by racial and ethnic identity and breast cancer subtypes. METHODS: Among 161,808 postmenopausal participants in Women's Health Initiative, eligible were a subsample of 27,393 postmenopausal women aged 50-79 years old, who enrolled from 1993 to 1998, had serum test biomarkers, and were followed for breast cancer incidence through February 2022. Allostatic load at enrollment was computed based on eight biomarkers from lab serum tests and a questionnaire about participants' prescription drug use. The associations between allostatic scores and risk of breast cancer (overall and by subtypes) were assessed using Cox proportional hazards models. The race and ethnic differences were examined. RESULTS: Over a median follow-up time of 17.24 years, 1722 invasive breast cancer cases were identified. High allostatic load was associated with an increased risk of breast cancer (HR = 1.36, 95%CI: 1.20, 1.54 for third tertile vs first tertile, Ptrend < 0.0001). Similar trends were found in White women and non-Hispanic women. Higher allostatic load was associated with hormone receptor-positive and HER2/Neu-negative breast cancer (HR = 1.54, 95%CI: 1.30, 1.80 for third tertile vs first tertile, Ptrend < 0.0001). CONCLUSION: In this study, we found that higher allostatic load was significantly associated with an increased risk of breast cancer in postmenopausal women.

Changes in physical function in older women with endometrial cancer with or without adjuvant therapy.

OBJECTIVE: To evaluate changes in physical function (PF) for older women with endometrial cancer (EC) + / - adjuvant therapy in the Women's Health Initiative Life and Longevity after Cancer cohort. MATERIALS AND METHODS: This study examined women ≥ 70 years of age with EC with available treatment records. Change in PF was measured using the RAND-36 and compared between groups using Wilcoxon rank-sum tests. Multivariable median regression was used to compare the changes in scores while adjusting for confounding variables. RESULTS: Included in the study were 287 women, 150 (52.3%) women who did not receive adjuvant therapy and 137 (47.7%) who received adjuvant therapy. When comparing PF scores, there was a statistically significant difference in the median percent change in functional decline, with a greater decline in those who received adjuvant therapy (- 5.9% [- 23.5 to 0%]) compared to those who did not (0 [- 18.8 to + 6.7%]), p = 0.02). Results were not statistically significant after multivariable adjustment, but women who underwent chemotherapy had a greater percent change (median ∆ - 13.8% [- 35.5 to 0%]) compared to those who received radiation alone (median ∆ - 5.9% [- 31.3 to 0%]) or chemotherapy and radiation (median ∆ - 6.5% [- 25.8 to + 5.7%]. CONCLUSIONS: Older women with EC who received adjuvant therapy experienced greater change in PF than those who did not receive adjuvant therapy, particularly women who received chemotherapy. These results were not statistically significant on multivariate analysis. IMPLICATIONS FOR CANCER SURVIVORS: EC survivors may experience changes in PF because of chemotherapy and/or radiation therapy. Additional supportive care may need to be provided to older women to mitigate functional decline.

Association of Later-Life Weight Changes With Survival to Ages 90, 95, and 100: The Women's Health Initiative.

BACKGROUND: Associations of weight changes and intentionality of weight loss with longevity are not well described. METHODS: Using longitudinal data from the Women's Health Initiative (N = 54 437; 61-81 years), we examined associations of weight changes and intentionality of weight loss with survival to ages 90, 95, and 100. Weight was measured at baseline, year 3, and year 10, and participants were classified as having weight loss (≥5% decrease from baseline), weight gain (≥5% increase from baseline), or stable weight (<5% change from baseline). Participants reported intentionality of weight loss at year 3. RESULTS: A total of 30 647 (56.3%) women survived to ≥90 years. After adjustment for relevant covariates, 3-year weight loss of ≥5% vs stable weight was associated with lower odds of survival to ages 90 (OR, 0.67; 95% CI, 0.64-0.71), 95 (OR, 0.65; 95% CI, 0.60-0.71), and 100 (OR, 0.62; 95% CI, 0.49-0.78). Compared to intentional weight loss, unintentional weight loss was more strongly associated with lower odds of survival to age 90 (OR, 0.83; 95% CI, 0.74-0.94 and OR, 0.49; 95% CI, 0.44-0.55, respectively). Three-year weight gain of ≥5% vs stable weight was not associated with survival to age 90, 95, or 100. The pattern of results was similar among normal weight, overweight, and obese women in body mass index (BMI)-stratified analyses. CONCLUSIONS: Weight loss of ≥5% vs stable weight was associated with lower odds of longevity, more strongly for unintentional weight loss than for intentional weight loss. Potential inaccuracy of self-reported intentionality of weight loss and residual confounding were limitations.

Quantification of Diffusive Methane Emissions from a Large Eutrophic Lake with Satellite Imagery.

Lakes are major emitters of methane (CH4); however, a longstanding challenge with quantifying the magnitude of emissions remains as a result of large spatial and temporal variability. This study was designed to address the issue using satellite remote sensing with the advantages of spatial coverage and temporal resolution. Using Aqua/MODIS imagery (2003-2020) and in situ measured data (2011-2017) in eutrophic Lake Taihu, we compared the performance of eight machine learning models to predict diffusive CH4 emissions and found that the random forest (RF) model achieved the best fitting accuracy (R2 = 0.65 and mean relative error = 21%). On the basis of input satellite variables (chlorophyll a, water surface temperature, diffuse attenuation coefficient, and photosynthetically active radiation), we assessed how and why they help predict the CH4 emissions with the RF model. Overall, these variables mechanistically controlled the emissions, leading to the model capturing well the variability of diffusive CH4 emissions from the lake. Additionally, we found climate warming and associated algal blooms boosted the long-term increase in the emissions via reconstructing historical (2003-2020) daily time series of CH4 emissions. This study demonstrates the great potential of satellites to map lake CH4 emissions by providing spatiotemporal continuous data, with new and timely insights into accurately understanding the magnitude of aquatic greenhouse gas emissions.

New-Onset Diabetes after an Obesity-Related Cancer Diagnosis and Survival Outcomes in the Women's Health Initiative.

BACKGROUND: Individuals diagnosed with an obesity-related cancer (ORC survivors) are at an elevated risk of incident diabetes compared with cancer-free individuals, but whether this confers survival disadvantage is unknown. METHODS: We assessed the rate of incident diabetes in ORC survivors and evaluated the association of incident diabetes with all-cause and cancer-specific mortality among females with ORC in the Women's Health Initiative cohort (N = 14,651). Cox proportional hazards regression models stratified by exposure-risk periods (0-1, >1-3, >3-5, >5-7, and >7-10 years) from ORC diagnosis and time-varying exposure (diabetes) analyses were performed. RESULTS: Among the ORC survivors, a total of 1.3% developed diabetes within ≤1 year of follow-up and 2.5%, 2.3%, 2.3%, and 3.6% at 1-3, 3-5, 5-7, and 7-10 years of follow-up, respectively, after an ORC diagnosis. The median survival for those diagnosed with diabetes within 1-year of cancer diagnosis and those with no diabetes diagnosis in that time frame was 8.8 [95% confidence interval (CI), 7.0-14.5) years and 16.6 (95% CI, 16.1-17.0) years, respectively. New-onset compared with no diabetes as a time-varying exposure was associated with higher risk of all-cause (HR, 1.27; 95% CI, 1.16-1.40) and cancer-specific (HR, 1.17; 95% CI, 0.99-1.38) mortality. When stratified by exposure-risk periods, incident diabetes in ≤1 year of follow-up was associated with higher all-cause (HR, 1.76; 95% CI, 1.40-2.20) and cancer-specific (HR0-1, 1.82; 95% CI, 1.28-2.57) mortality, compared with no diabetes diagnosis. CONCLUSIONS: Incident diabetes was associated with worse cancer-specific and all-cause survival, particularly in the year after cancer diagnosis. IMPACT: These findings draw attention to the importance of diabetes prevention efforts among cancer survivors to improve survival outcomes.

Sex-Specific Associations between Adiponectin and Leptin Signaling and Pancreatic Cancer Survival.

BACKGROUND: Circulating adiponectin and leptin have been associated with risk of pancreatic cancer. However, the relationship between long-term exposure to these adipokines in the prediagnostic period with patient survival has not been investigated. METHODS: Adipokine levels were measured in prospectively collected samples from 472 patients with pancreatic cancer. Because of sex-specific differences in adipokine levels, associations were evaluated separately for men and women. In a subset of 415 patients, we genotyped 23 SNPs in adiponectin receptor genes (ADIPOR1 and ADIPOR2) and 30 SNPs in the leptin receptor gene (LEPR). RESULTS: Adiponectin levels were inversely associated with survival in women [HR, 1.71; 95% confidence interval (CI), 1.15-2.54]; comparing top with bottom quartile but not in men (HR, 0.89; 95% CI, 0.46-1.70). The SNPs rs10753929 and rs1418445 in ADIPOR1 were associated with survival in the combined population (per minor allele HR, 0.66; 95% CI, 0.51-0.84, and HR, 1.33; 95% CI, 1.12-1.58, respectively). Among SNPs in LEPR, rs12025906, rs3790431, and rs17127601 were associated with survival in the combined population [HRs, 1.54 (95% CI, 1.25-1.90), 0.72 (95% CI, 0.59-0.88), and 0.70 (95% CI, 0.56-0.89), respectively], whereas rs11585329 was associated with survival in men only (HR, 0.39; 95% CI, 0.23-0.66; Pinteraction = 0.0002). CONCLUSIONS: High levels of adiponectin in the prediagnostic period were associated with shorter survival among women, but not among men with pancreatic cancer. Several polymorphisms in ADIPOR1 and LEPR are associated with patient survival. IMPACT: Our findings reveal the association between adipokine signaling and pancreatic cancer survival and demonstrate the importance of examining obesity-associated pathways in relation to pancreatic cancer in a sex-specific manner.

Diets with Higher Anti-inflammatory Potential Associated with Lower Risk of Development of Nonalcoholic Fatty Liver Disease and Early-Stage of Fibrosis Among US Adults.

BACKGROUND: There is limited evidence of how dietary inflammatory potential influences nonalcoholic fatty liver disease (NAFLD) progression. AIMS: Our study aims to evaluate the association of dietary inflammatory index (DII) with liver fibrosis, a hallmark feature of NAFLD, among US adults. METHODS: Cross-sectional data consisting of 5,506 participants in the National Health and Nutrition Examination Survey from 2011 to 2018 were used. Energy adjusted-DII (E-DII) scores were calculated using 2 days of 24-h dietary recall data. We used a partial proportional odds model to determine risk at each stage of fibrosis according to the E-DII score. RESULTS: The weighted prevalence of NAFLD (assessed by US fatty liver index) was 34.5%, with 23.2% (assessed by NAFLD Fibrosis Score) having mild fibrosis, 10.4% intermediate fibrosis, and 0.9% advanced fibrosis. When comparing the most pro-inflammatory diets to the most anti-inflammatory diets (AIDs) in the multivariable model, the marginal probability effect (MPE) of NAFLD, mild fibrosis and intermediate fibrosis increased by 11.7% (95% CI 6.6%, 16.9%), 7.0% (95% CI 3.5%, 10.4%) and 4.0% (95% CI 0.3%, 7.5%), respectively. The MPE of advanced fibrosis was not significant (MPE = 0.7%; 95% CI - 1.1%, 2.8%). Similar associations were observed when applying Fibrosis-4 and transient elastography as fibrosis diagnostic measurements. CONCLUSIONS: An AID was associated with lower risk of development of NAFLD and early-stage of fibrosis among US adults. But the associations became attenuated and dissipated as the fibrogenesis became severe. Further studies are needed to re-confirm our observations.