Medicine
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Multicenter Study Observational Study
STK39 and WNK1 Are Potential Hypertension Susceptibility Genes in the BELHYPGEN Cohort.
The serine/threonine kinase With-No-Lysine (K) Kinase 1 (WNK1) activates the thiazide-sensitive Na(+)/Cl(-) cotransporter through phosphorylation of STE20/SPS1-related proline/alanine-rich kinase, another serine/threonine kinase encoded by STK39. The aim of this study was to look for association between WNK1 and STK39 gene variants, and blood pressure (BP) and hypertension. Seven hundred seventy-nine Caucasian hypertensive patients (HYP) recruited in 6 academic centers from Belgium, and 906 normotensive (NT) controls were genotyped for 5 single nucleotide polymorphisms-rs3754777, rs6749447, rs35929607 (STK39), rs1468326, and rs765250 (WNK1)-using the Snapshot method. ⋯ In the whole cohort, a dose-dependent increase in systolic BP was observed according to the number of at-risk genotypes (0: 129.8 mm Hg; 1: 133.0 mm Hg; 2: 149.3 mm Hg, P = 0.02). Single nucleotide polymorphisms rs3754777 (STK39) and rs1468326 (WNK1) were associated with hypertension and BP in our multicenter Belgian case-control study, which supports the role of STK39 and WNK1 as potential hypertension susceptibility genes. Replication in different clinical settings and study of other candidate loci belonging to the same molecular pathway is warranted.
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Randomized Controlled Trial
Is It Possible to Shorten the Duration of Adjuvant Chemotherapy for Locally Advanced Rectal Cancer?
The long duration of 4 months of postoperative adjuvant chemotherapy is currently recommended for locally advanced rectal cancer after preoperative chemoradiation and surgery. Whether a short duration could be applied in these patients is unknown. So, the purpose of this study is to evaluate the effects on prognosis based on different durations of adjuvant chemotherapy for rectal cancer. ⋯ Multivariable analysis indicated that long duration of adjuvant chemotherapy is significantly associated with longer distant metastasis-free survival in patients with ypIII stage, but not in those with ypII stage. A long duration of at least 2 months of postoperative adjuvant chemotherapy is necessary for patients with ypIII stage, whereas it may not be absolutely appropriate for those with ypII stage. Therefore, we suggest a tailored selection of durations of adjuvant chemotherapy for locally advanced rectal cancer.
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Multicenter Study
Attribution to Heterogeneous Risk Factors for Breast Cancer Subtypes Based on Hormone Receptor and Human Epidermal Growth Factor 2 Receptor Expression in Korea.
We conducted a heterogeneous risk assessment of breast cancer based on the hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) calculating the risks and population-based attributable fractions (PAFs) for modifiable and nonmodifiable factors. Using matched case-control study design from the Seoul Breast Cancer Study and the national prevalence of exposure, the risks and PAFs for modifiable and nonmodifiable factors were estimated for total breast cancers and subtypes. The attribution to modifiable factors was different for each subtype (luminal A, PAF = 61.4% [95% confidence interval, CI = 54.3%-69.8%]; luminal B, 21.4% [95% CI = 18.6-24.9%]; HER2-overexpression, 59.4% [95% CI = 47.8%-74.3%], and triple negative tumors [TNs], 27.1% [95% CI = 22.9%-32.4%)], and the attribution to the modifiable factors for the luminal A and HER2-overexpression subtypes was higher than that of the luminal B and TN subtypes (P heterogeneity ≤ 0.001). ⋯ Total reproductive factors were also heterogeneously attributed to each breast cancer subtype (luminal A, 65.4%; luminal B, 24.1%; HER2-overexpression, 57.9%, and TN subtypes, -3.1%; P heterogeneity ≤ 0.001). Each pathological subtype of breast cancer by HRs and HER2 status may be associated with heterogeneous risk factors and their attributable risk, suggesting a different etiology. The luminal B and TN subtypes seemed to be less preventable despite intervention for alleged risk factors, even though physical activity had a high preventable potential against breast cancer.
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Multicenter Study
Tooth Loss and Metabolic Syndrome in South Korea: The 2012 Korean National Health and Nutrition Examination Survey.
To evaluate the relationship between tooth loss and metabolic syndrome (MS) in South Korean adults. ⋯ A total of 3589 adults (1511 men and 2078 women aged over 40 years) from the 2012 Korean National Health and Nutrition Examination Survey were included and divided into 3 groups according to the number of remaining teeth (0-19, 20-27, and 28). We recorded the number of remaining teeth and measured MS components such as waist circumference, systolic and diastolic blood pressure, fasting blood glucose, serum high-density lipoprotein-cholesterol, and triglyceride concentration. We also calculated the number of subjects who met the inclusion criteria of MS in each group. Multiple logistic regression analysis was performed to estimate the prevalence of MS components according to the number of remaining teeth after adjusting for covariates. Women without MS had significantly more teeth than those with MS (24.5 ± 0.2 vs 21.0 ± 0.3). In men, the prevalence of high blood pressure and high fasting blood glucose levels were significantly different among the 3 groups (P = 0.003 and P < 0.001, respectively); however, the prevalence of MS and all MS components were significantly different in women (P < 0.001 for all comparisons). Men with 0 to 19 remaining teeth were most likely to have high blood pressure and high fasting blood glucose, while women with 0 to 19 remaining teeth had the highest prevalence of MS and each MS component. Multiple logistic regression analysis revealed that women with fewer remaining teeth had a higher prevalence of MS and MS components after adjusting for covariates. Having only a few remaining teeth was associated with MS in women in South Korea.
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Wnt/β-catenin signaling pathway is thought to be implicated in the development of arterial stiffness and vascular calcification. As a Wnt signaling pathway inhibitor, it is interesting to investigate whether sclerostin or dickkopf-1 (DKK1) level is correlated with arterial stiffness in renal transplant (RT) recipients. Fasting blood samples were obtained for biochemical data, sclerostin, DKK1, and osteoprotegerin (OPG) determinations. ⋯ Compared with patients in the low arterial stiffness group, patients in the high arterial stiffness group had higher prevalence of hypertension (P = 0.002), diabetes (P < 0.001), metabolic syndrome (P = 0.025), longer posttransplant duration (P = 0.005), higher systolic blood pressure (P < 0.001) and diastolic blood pressure (P = 0.018), and higher fasting glucose (P = 0.004), total cholesterol (P = 0.042), blood urea nitrogen (P = 0.020), phosphorus (P = 0.042), and sclerostin levels (P = 0.001). According to our multivariable forward stepwise linear regression analysis, age (β = 0.272, P = 0.014), phosphorus (β = 0.308, P = 0.007), and logarithmically-transformed OPG (log-OPG; β = 0.222, P = 0.046) were positively associated with sclerostin levels, and multivariate logistic regression analysis, sclerostin (odds ratio 1.052, 95% confidence interval 1.007-1.099, P = 0.024), and posttransplant duration (odds ratio 1.024, 95% confidence interval 1.004-1.045, P = 0.019) were the independent predictors of peripheral arterial stiffness in RT recipients. In this study, serum sclerostin level, but not DKK1, was proved to be involved in the pathogenetic process of peripheral arterial stiffness in RT recipients.