A common variant of the MACC1 gene is significantly associated with overall survival in colorectal cancer patients

<p>Abstract</p> <p>Background</p> <p>The newly discovered metastasis-associated in colon cancer-1 (MACC1) gene is a key regulator of the HGF/MET pathway. Deregulation of HGF/MET signaling is reported as a prognostic marker for tumorigenesis, early stage invasion, and metastasis. High expression levels of MACC1 have been associated with colon cancer metastasis and reduced survival. Potential links between the genetic diversity of the MACC1 locus and overall survival are unknown. We therefore investigated the association between MACC1 tagging single nucleotide polymorphisms (SNPs) and overall survival in a large cohort of colorectal cancer patients.</p> <p>Methods</p> <p>The study included 318 subjects with histopathologically proven colorectal cancer at the Academic Teaching Hospital Feldkirch, Austria. Survival data were provided by the federal agency for statistics in Austria. Genomic DNA was isolated from formalin-fixed paraffin-embedded specimens; six tagging SNPs (rs1990172, rs3114446, rs10275612, rs3095007, rs3095009, and rs7780032), capturing most of the common variants of the MACC1 locus, were genotyped by SNaPshot assays.</p> <p>Results</p> <p>Over a mean follow up period of 5.3 (± 1.0) years, 94 deaths were recorded. Carriers of the G-allele of SNP rs1990172 showed a significantly decreased overall survival (additive HR = 1.38 [1.05-1.82]; <it>p </it>= 0.023). Multivariate analysis adjusted for age and UICC tumor stage confirmed this result (HR = 1.49 [1.12-1.98]; <it>p </it>= 0.007). Other investigated genetic variants of the MACC1 gene were not significantly associated with overall survival (<it>p</it>-values > 0.05).</p> <p>Conclusions</p> <p>For the first time, our study investigated the influence of MACC1 tagging polymorphisms on overall survival suggesting SNP rs1990172 as a predictor for reduced overall survival in colorectal cancer patients. Further studies will be required to validate our findings.</p

Apolipoprotein C3 Polymorphisms, Cognitive Function and Diabetes in Caribbean Origin Hispanics

Apolipoprotein C3 (APOC3) modulates triglyceride metabolism through inhibition of lipoprotein lipase, but is itself regulated by insulin, so that APOC3 represents a potential mechanism by which glucose metabolism may affect lipid metabolism. Unfavorable lipoprotein profiles and impaired glucose metabolism are linked to cognitive decline, and all three conditions may decrease lifespan. Associations between apolipoprotein C3 (APOC3) gene polymorphisms and impaired lipid and glucose metabolism are well-established, but potential connections between APOC3 polymorphisms, cognitive decline and diabetes deserve further attention.We examined whether APOC3 single nucleotide polymorphisms (SNPs) m482 (rs2854117) and 3u386 (rs5128) were related to cognitive measures, whether the associations between cognitive differences and genotype were related to metabolic differences, and how diabetes status affected these associations. Study subjects were Hispanics of Caribbean origin (n = 991, aged 45-74) living in the Boston metropolitan area.Cognitive and metabolic measures differed substantially by type II diabetes status. In multivariate regression models, APOC3 m482 AA subjects with diabetes exhibited lower executive function (P = 0.009), Stroop color naming score (P = 0.014) and Stroop color-word score (P = 0.022) compared to AG/GG subjects. APOC3 m482 AA subjects with diabetes exhibited significantly higher glucose (P = 0.032) and total cholesterol (P = 0.028) compared to AG/GG subjects. APOC3 3u386 GC/GG subjects with diabetes exhibited significantly higher triglyceride (P = 0.004), total cholesterol (P = 0.003) and glucose (P = 0.016) compared to CC subjects.In summary, we identified significant associations between APOC3 polymorphisms, impaired cognition and metabolic dysregulation in Caribbean Hispanics with diabetes. Further research investigating these relationships in other populations is warranted

Data on the association of serum glypican-4 with prevalent and future kidney function

The present study included 456 patients who were referred to elective coronary angiography. Serum GPC4 levels were measured with a commercially available ELSIA kit. Glomerular filtration rate (GFR) was estimated (eGFR) using the ‘Chronic Kidney Disease Epidemiology Collaboration’ (CKD-EPI) serum creatinine equation. GFR categories were defined as follows: G1: eGFR≥90 mL/min/1.73 m2; G2: eGFR=60-89 mL/min/1.73 m2; G3a: eGFR=45-59 mL/min/1.73 m2; G3b: eGFR=30-44 mL/min/1.73 m2; G4: eGFR=15-29 mL/min/1.73 m2. Urinary albumin excretion was expressed as ACR in a random morning urine specimen. ACR levels lower than 30 mg/g (category A1) were defined as normal and albuminuria was diagnosed as an ACR of 30 mg/g or greater. CKD was diagnosed in case of eGFR ˂ 60 mL/min/1.73 m2 or albuminuria. After a mean period of 3.5 years, patients were re-invited to undergo a follow-up investigation and kidney function was reassessed. The Table includes baseline characteristics and GPC4 values as well as parameters of kidney function.THIS DATASET IS ARCHIVED AT DANS/EASY, BUT NOT ACCESSIBLE HERE. TO VIEW A LIST OF FILES AND ACCESS THE FILES IN THIS DATASET CLICK ON THE DOI-LINK ABOV

Data on the association of serum glypican-4 with future major adverse cardiovascular events and mortality in patients undergoing coronary angiography

The present study included 760 patients who were referred to elective coronary angiography. Data were recorded by standardized interviews and by standardized examination protocols at our institution and were extracted from medical records. Serum GPC4 levels were measured with a commercially available ELSIA kit. During a follow up period the incidence of MACE, vascular mortality, and all-cause mortality were recorded. The Table includes baseline characteristics and GPC4 values as well as the endpoints major adverse cardiovascular events, vascular mortality, and all-cause mortality occurred during the follow-up period. GPC4 is given as ng/ml as well as z-transformed variable. Furthermore, GPC4 was categorized according to the optimal predictive cut-off value for GPC4. “Sex” describes the biological sex of subjects, whereas “0” stands for “male” and “1” for “female” patients. For other categorical variables“0” encodes “no” and “1” stands for “yes”.THIS DATASET IS ARCHIVED AT DANS/EASY, BUT NOT ACCESSIBLE HERE. TO VIEW A LIST OF FILES AND ACCESS THE FILES IN THIS DATASET CLICK ON THE DOI-LINK ABOV