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. 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. 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. 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.

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.

Bilateral breast cancer (BBC) poses a major challenge for oncologists because of the cryptic relationship between the two lesions. The purpose of this study was to determine the origin of the contralateral breast cancer (either dependent or independent of the index tumor). Here, we used ultra-deep whole-exome sequencing and array comparative genomic hybridization (aCGH) to study four paired samples of BBCs with different tumor subtypes and time intervals between the developments of each tumor. We used two paired primary breast tumors and corresponding metastatic liver lesions as the control. We tested the origin independent nature of BBC in three ways: mutational concordance, mutational signature clustering, and clonality analysis using copy number profiles. We found that the paired BBC samples had near-zero concordant mutation rates, which were much lower than those of the paired primary/metastasis samples. The results of a mutational signature analysis also suggested that BBCs are independent of one another. A clonality analysis using aCGH data further revealed that paired BBC samples was clonally independent, in contrast to clonal related origin found for paired primary/metastasis samples. Our preliminary findings show that BBCs in Han Chinese women are origin independent and thus should be treated separately.