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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]

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]