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Background/Objectives:To assess the distribution of interleukin (IL)-1β, IL-6, tumour necrosis factor (TNF)-α and C-reactive protein (CRP) according to the different definitions of metabolically healthy obesity (MHO).Subjects/Methods:A total of 881 obese (body mass index (BMI) 30 kg/m2) subjects derived from the population-based CoLaus Study participated in this study. MHO was defined using six sets of criteria including different combinations of waist, blood pressure, total high-density lipoprotein cholesterol or low-density lipoprotein -cholesterol, triglycerides, fasting glucose, homeostasis model, high-sensitivity CRP, and personal history of cardiovascular, respiratory or metabolic diseases. IL-1β, IL-6 and TNF-α were assessed by multiplexed flow cytometric assay. CRP was assessed by immunoassay.Results:On bivariate analysis some, but not all, definitions of MHO led to significantly lower levels of IL-6, TNF-α and CRP compared with non-MH obese subjects. Most of these differences became nonsignificant after multivariate analysis. An posteriori analysis showed a statistical power between 9 and 79%, depending on the inflammatory biomarker and MHO definition considered. Further increasing sample size to overweight+obese individuals (BMI25 kg/m2, n=2917) showed metabolically healthy status to be significantly associated with lower levels of CRP, while no association was found for IL-1β. Significantly lower IL-6 and TNF-α levels were also found with some but not all MHO definitions, the differences in IL-6 becoming nonsignificant after adjusting for abdominal obesity or percent body fat.Conclusions:MHO individuals present with decreased levels of CRP and, depending on MHO definition, also with decreased levels in IL-6 and TNF-α. Conversely, no association with IL-1β levels was found. [ABSTRACT FROM AUTHOR]

Objective:To estimate the prevalence of metabolically healthy obesity (MHO) according to different definitions.Methods:Population-based sample of 2803 women and 2557 men participated in the study. Metabolic abnormalities were defined using six sets of criteria, which included different combinations of the following: waist; blood pressure; total, high-density lipoprotein or low-density lipoprotein-cholesterol; triglycerides; fasting glucose; homeostasis model assessment; high-sensitivity C-reactive protein; personal history of cardiovascular, respiratory or metabolic diseases. For each set, prevalence of MHO was assessed for body mass index (BMI); waist or percent body fat.Results:Among obese (BMI 30 kg/m2) participants, prevalence of MHO ranged between 3.3 and 32.1% in men and between 11.4 and 43.3% in women according to the criteria used. Using abdominal obesity, prevalence of MHO ranged between 5.7 and 36.7% (men) and 12.2 and 57.5% (women). Using percent body fat led to a prevalence of MHO ranging between 6.4 and 43.1% (men) and 12.0 and 55.5% (women). MHO participants had a lower odd of presenting a family history of type 2 diabetes. After multivariate adjustment, the odds of presenting with MHO decreased with increasing age, whereas no relationship was found with gender, alcohol consumption or tobacco smoking using most sets of criteria. Physical activity was positively related, whereas increased waist was negatively related with BMI-defined MHO.Conclusion:MHO prevalence varies considerably according to the criteria used, underscoring the need for a standard definition of this metabolic entity. Physical activity increases the likelihood of presenting with MHO, and MHO is associated with a lower prevalence of family history of type 2 diabetes. [ABSTRACT FROM AUTHOR]

The EPH/EFN family of receptor tyrosine kinases regulates cell adhesion and migration and has an important role in controlling cell positioning in the normal intestinal epithelium. Inactivation of EPHB2 has recently been shown to accelerate tumorigenesis in the colon and rectum, and we have previously demonstrated frequent frameshift mutations (41%) in an A9 coding microsatellite repeat in exon 17 of EPHB2 in colorectal tumors with microsatellite instability (MSI). In this study, we extended these analyses to extracolonic MSI cancers, and found frameshift EPHB2 mutations in 39% (25/64) of gastric tumors and 14% (8/56) of endometrial tumors. Regression analysis of these EPHB2 mutation data on the basis of our previously proposed statistical model identified EPHB2 as a selective target of frameshift mutations in MSI gastric cancers but not in MSI endometrial carcinomas. These results suggest a functional role for EPHB2 in gastric tumor progression, and emphasize the differences between the tumorigenic processes in MSI gastrointestinal and endometrial cancer.Oncogene (2007) 26, 308–311. doi:10.1038/sj.onc.1209780; published online 3 July 2006 [ABSTRACT FROM AUTHOR]

In sporadic colorectal cancer (CRC), KRAS are alternative to BRAF mutations and occur, respectively, in 30 and 10% of cases. Few reports addressed the association between KRAS–BRAF mutations and tumour progression specifically in sporadic microsatellite-stable (MSS) CRC. We screened KRAS and BRAF in 250 MSS primary CRC and 45 lymph node (LN) metastases and analysed the pathological features of the cases to understand the involvement of KRAS–BRAF activation in progression and metastasis. Forty-five per cent of primary MSS CRCs carried mutations in at least one of these genes and mutations were associated with wall invasion (P=0.02), presence and number of LN metastases (P=0.02 and P=0.03, respectively), distant metastases (P=0.004) and advanced stage (P=0.01). We demonstrated that KRAS and BRAF are alternative events in Tis and T1 MSS CRC and, KRAS rather than BRAF mutations, contributed to the progression of MSS CRC. The frequency of KRAS and/or BRAF mutations was higher in LN metastases than in primary carcinomas (P=0.0002). Mutated LN metastases displayed KRAS associated or not with BRAF mutations. BRAF mutations were never present as a single event. Concomitant KRAS and BRAF mutations increased along progression of MSS CRCs, suggesting that activation of both genes is likely to harbour a synergistic effect.Oncogene (2007) 26, 158–163. doi:10.1038/sj.onc.1209758; published online 4 September 2006 [ABSTRACT FROM AUTHOR]