Search

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. [ABSTRACT FROM AUTHOR]

Background: Plant-based dietary patterns may affect colorectal cancer (CRC) related outcomes, while risks differ in the quality of plant foods. We aimed to examine the association of plant-based diet quality with risks of CRC incidence and mortality and whether this association was modified by genetic risk. Methods: This prospective cohort study included 186,675 participants free of cancer when the last dietary recall was completed. We calculated three plant-based diet indices (PDIs), i.e., the overall plant-based diet index (PDI), the healthful plant-based diet index (hPDI), and the unhealthful plant-based diet index (uPDI) representing adherence to plant-based diets with diverse quality. Genetic risk was characterized using a weighted polygenic risk score (PRS), capturing overall risk variants associated with CRC. Hazard ratios (HR) and 95% confidential intervals (CI) were estimated by the cause-specific Cox proportional hazards model. Results: Over a follow-up of 9.5 years, 2163 cases and 466 deaths from CRC were documented. The HR of CRC incidence was 0.88 (95% CI, 0.81–0.96) and 0.91 (95% CI, 0.84–0.99) per 10-score increase in PDI and hPDI, respectively. Compared to the lowest quartile, PDI, hPDI, and uPDI in the highest quartile were associated with a 13% decrease, a 15% decrease, and a 14% increase in risk of incident CRC, respectively. We found a joint association of genetic risk and PDIs with incident CRC, with the highest hazard observed in those carrying higher PRS and adhering to lower-quality PDIs. The inverse association of PDI and hPDI with CRC mortality was pronounced in males. Conclusions: Our results suggested that better adherence to overall and healthful plant-based diets was associated with a lower risk of CRC, whereas an unhealthful plant-based diet was associated with a higher CRC risk. Consumption of a higher-quality plant-based diet combined with decreased genetic risk conferred less susceptibility to CRC. Our findings highlighted the importance of food quality when adhering to a plant-based dietary pattern for CRC prevention in the general population. [ABSTRACT FROM AUTHOR]

Background: Klotho has both anticancer and hormone‐like functions. But the research on Klotho and cancer is mainly based on animal experiments and small‐scale clinical research, thus we explored the association between serum Klotho and cancer and cancer mortality based on the National Health and Nutrition Survey (NHANES). Methods: Participants were employed from the NHANES 2007–2016, excluding pregnant, chronic renal insufficiency, and incomplete data of cancer questionnaire and serum Klotho level. The association of serum Klotho with cancer and mortality was analyzed by weighted Logistic regression, weighted Cox regression and competitive risk model, respectively. Correlations between serum Klotho and testosterone and estradiol levels were analyzed by Spearman correlation and restricted cubic spline respectively. Results: We found Klotho had an inverse effect with risk of pan‐cancer (all p < 0.02), with each unit increase in Klotho (1ug/g creatinine) associated with a 0.9%–2.2% reduction in the risk of cancer, and higher levels showing a stronger negative association (all p‐trend <= 0.0005). Whereas, we did not observe any association between serum Klotho level with all‐cause mortality and cancer‐specific mortality (all p > 0.05). Then, stratified analysis found that people aged 60–79, female, overweight and non‐Hispanic whites or Mexican Americans were less likely to develop cancer. In addition, there was a strong nonlinear and linear positive correlation of Klotho with estradiol (p‐nonlinear = 0.0178) and testosterone only among male participants (β = −0.513, p = 0.0137), respectively. Conclusions: We found an inverse association between serum Klotho and cancer, but without cancer mortality. And this effect may be partially mediated by estradiol and testosterone. Further prospective studies are needed to prove these findings. [ABSTRACT FROM AUTHOR]

Simple Summary: The large-scale population-based evidence exploring genetically modified circulating levels of advanced glycation end-products (AGEs) and their receptor (RAGE) with risk and mortality of breast cancer is scarce. We aimed to evaluate the role of plasma AGEs, soluble RAGE (sRAGE), and AGEs/sRAGE-ratio level, as well as their interactions with a genetic predisposition in their metabolism-related genes on breast cancer. Higher levels of AGEs and AGEs/sRAGE-ratio were associated with an increased risk of breast cancer, but sRAGE levels were negatively associated with breast cancer risk. We also observed a positive association between AGEs and the bad prognosis of breast cancer. Although we did not observe a significant contribution of genetic variants to breast cancer risk, rs2070600 and rs1800624 in the AGER gene were dose-dependently correlated with sRAGE levels. Further, compared to the haplotype CT at the lowest quartile of AGEs, haplotypes TT and TA were prominently associated with breast cancer risk in the highest quartile of AGEs. This study emphasized the potential of the AGE-RAGE axis as a new biomarker of breast cancer in the future and aided in screening a high-risk population with breast cancer. The interaction of advanced glycation end-products (AGEs) with their receptor (RAGE) elicits oxidative stress and inflammation, which is involved in the development of breast cancer. However, large-scale population-based evidence exploring genetically modified circulating levels of AGEs-RAGE axis with risk and mortality of breast cancer is scarce. We recruited 1051 pairs of age-matched breast cancers and controls and measured plasma AGEs and sRAGE concentrations by enzyme-linked immunosorbent assay (ELISA). Multivariate logistic regression and Cox proportional hazard model were used to calculate the effects of plasma levels and genetic variants of the AGEs-RAGE axis and their combined effects on breast cancer risk and prognosis, respectively. Furthermore, linear regression was performed to assess the modifications in plasma AGEs/sRAGE levels by genetic predisposition. Higher levels of AGEs and AGEs/sRAGE-ratio were associated with an increased risk of breast cancer, but sRAGE levels were negatively associated with breast cancer risk, especially in women <60 years. We also observed a positive association between AGEs and the bad prognosis of breast cancer. Although we did not observe a significant contribution of genetic variants to breast cancer risk, rs2070600 and rs1800624 in the AGER gene were dose-dependently correlated with sRAGE levels. Further, compared to the haplotype CT at the lowest quartile of AGEs, haplotypes TT and TA were prominently associated with breast cancer risk in the highest quartile of AGEs. This study depicted a significant association between circulating levels of AGEs-RAGE axis and breast cancer risk and mortality and revealed the potential of plasma AGEs, especially coupled with AGER polymorphism as biomarkers of breast cancer. [ABSTRACT FROM AUTHOR]

Purpose: We aimed to explore the association of chronic constipation and diarrhea with major chronic diseases including cancer, cardiovascular disease (CVD), and diabetes, as well as with mortality risk. In addition, we characterized the interrelationship of inflammation with abnormal bowel health, major chronic diseases, and mortality.Methods: Demographic characteristics, physical and laboratory examinations were collected from the National Health and Nutrition Examination Survey (NHANES) database 2005-2010. Chronic constipation or diarrhea was diagnosed by the shape and frequency of defecation. The number of samples used for the cancer, CVD, diabetes, and mortality analyses were 11,217, 11,168, 11,555, and 14,316, respectively. Logistic regression was used to analyze the association among abnormal bowel health, major chronic diseases, dietary inflammatory index (DII), and C-reactive protein (CRP). A Cox proportional hazard regression was performed to assess risk of all-cause mortality, and the Fine and Gray models were subsequently employed to calculate the cancer and CVD mortality risks.Results: There were statistically positive associations of chronic diarrhea or constipation with breast and colon cancer, CVD, risks of all-cause mortality, and CVD mortality. Particularly in participants younger than 60, in addition to the positive correlations of chronic diarrhea with three major chronic diseases and all-cause mortality risk, chronic constipation also contributed to an elevated risk of CVD mortality. With respect to inflammation markers, an increased DII or CRP level was significantly associated with a higher prevalence of abnormal bowel health and major chronic diseases, and a higher mortality risk.Conclusions: Participants with abnormal bowel health were more likely linked to breast cancer, colon cancer, CVD, and risks of all-cause and CVD mortality. Moreover, inflammation may have a potential role in associations among abnormal bowel health, major chronic diseases and mortality. However, these findings need to be confirmed by further prospective studies. [ABSTRACT FROM AUTHOR]

Walking pace is associated with risks of major chronic diseases including cancer, cardiovascular disease (CVD) and diabetes mellitus type 2 (T2DM) in the general population. However, whether increasing walking pace could reduce risks of major chronic diseases in individuals with hypertension remains to be explored, and the underlying mechanism potentially mediated by low-grade inflammation is also unclear. A total of 160,470 participants with hypertension were included based on the UK Biobank. The relationships of the walking pace and low-grade inflammation with risks of major chronic diseases in individuals with hypertension were assessed by the Cox proportional hazards model. Mediation analyses were performed to investigate the contribution of low-grade inflammation to the association between walking pace and risks of major chronic diseases. Individuals with hypertension at the brisk walking pace had decreased risks of overall cancer and site-specific cancers (liver, lung, and endometrial cancers), all CVD events (angina, atrial fibrillation, heart failure, myocardial infarction, peripheral vascular disease and stroke), and T2DM (hazard ratios: 0.42–0.91). Increasing low-grade inflammation was associated with higher risks of aforementioned diseases except liver cancer and atrial fibrillation. Furthermore, low-grade inflammation partially mediated associations of the walking pace with risks of lung cancer, T2DM, and all CVD events (except atrial fibrillation), with mediation proportion of 2.0%–9.8%. Brisk walking pace was linked to reduced risks of major chronic diseases in individuals with hypertension, partially mediated by low-grade inflammation. Improving walking pace may be beneficial for health in individuals with hypertension. • The study was the first to examine relationships between walking pace with major chronic diseases risks in hypertension. • Brisk walking pace related to lower risks of cancer, cardiovascular disease and type 2 diabetes in hypertension. • Low-grade inflammation partially mediated associations of walking pace with major chronic disease risks in hypertension. [ABSTRACT FROM AUTHOR]

Aging is a risk factor for cancer incidence and mortality. Biological aging can reflect the aging degree of the body better than chronological age and can be aggravated by unhealthy lifestyle factors. We aimed to assess the joint effect of biological aging and lifestyle with risks of cancer incidence and mortality. This study included a total of 281,889 participants aged 37 to 73 from the UK Biobank database. Biological age was derived from chronological age and 9 clinical blood indicators, and lifestyle score was constructed by body mass index, smoking status, alcohol consumption, physical activity, and diet. Multivariate Cox hazard proportional regression model was used to analyze the independent and joint association of biological aging and lifestyle with risks of cancer incidence and mortality, respectively. Over a median follow-up period of 12.3 years, we found that older biological age was associated with increased risks of overall cancer, digestive system cancers, lung, breast and renal cancers incidence and mortality (HRs: 1.12–2.25). In the joint analysis of biological aging and lifestyle with risks of cancer incidence and mortality, compared with unhealthy lifestyle and younger biological age, individuals with healthy lifestyle and older biological age had decreased risks of incidence (8% ∼ 60%) and mortality (20% ∼ 63%) for overall, esophageal, colorectal, pancreatic and lung cancers. Biological aging may be an important risk factor for cancer morbidity and mortality. A healthier lifestyle is more likely to mitigate the adverse effects of biological aging on overall cancer and some site-specific cancers. • This study assessed the impact of biological aging base on phenotypic age on cancer. • Biological aging was associated with increased cancer morbidity and mortality. • Healthy lifestyle facilitated cancer prevention in individuals with biological aging. [ABSTRACT FROM AUTHOR]

Evidence regarding the role of physical frailty in cancer-related outcomes is limited. We aimed to examine the association of frailty with cancer incidence and mortality risk. This prospective study included 348,144 participants free of cancer at baseline from the UK Biobank. Frailty phenotypes (non-frail, pre-frail, and frail) were constructed from 5 components: weight loss, exhaustion, low physical activity, slow gait speed, and low grip strength. The outcome was incidence and mortality of overall and cite-specific cancers. Cox proportional hazard regression was used to estimate the association of frailty phenotypes with cancer incidence and mortality risk. A total of 43,304 incident cancer cases and 10,152 cancer deaths were documented during a median of 12.0 years of follow-up. For overall cancer, compared with non-frailty, the incidence risk increased by 4% for pre-frailty and 11% for frailty, and the mortality risk increased by 11% for pre-frailty and 39% for frailty. Frailty phenotypes were also dose-dependently associated with a higher risk of incidence and mortality of some site-specific cancers (including liver and lung), with significant sex differences. We observed a synergetic association of frailty phenotypes and smoking with overall cancer incidence and mortality risk. Frailty phenotypes contributed significantly to a higher risk of overall and some site-specific cancers incidence and mortality in a stepwise manner or within individual categories. Future studies are warranted to emphasize the identification, management and prevention of frailty in the whole population and complements of lifestyle-targeted interventions such as quitting smoking. • Evidence about the associations of frailty with cancer outcomes are insufficient. • Pre-frailty and frailty contributed to higher overall and site-specific cancer risks. • A synergetic effect between frailty phenotypes and smoking existed. [ABSTRACT FROM AUTHOR]