Disease Markers - Volume 28, issue 6

Authors: Zhao, Yanfang | Wang, Rui | Ma, Xiuqiang | Yan, Xiaoyan | Zhang, Zhansai | He, Xiang | He, Jia

Article Type: Research Article

Abstract: C-reactive protein (CRP) levels vary remarkably with ethnic status. Its distribution and correlates should be investigated across diverse populations, and these were limited in a representative Chinese population. We investigated 3133 participants aged 18–80 years in Shanghai, which were sampled using a randomized, stratified, multi-stage sampling method. The distribution of CRP was highly skewed toward a lower level. The median CRP was 0.55 mg/L (0.61 mg/L in males, 0.51 mg/L in females). Participants living in …urban region had higher CRP levels than those in rural region (0.67 vs. 0.46 mg/L). CRP levels showed significant correlation with traditional cardiovascular risk factors, and it was most strongly correlated with body mass index. Multivariate logistic regression analyses indicated that elevated CRP (being in the top 15 percentile of CRP; CRP ⩾ 2.09 mg/L) was significantly associated with obesity, hypertension, diabetes, low high-density lipoprotein cholesterol, high low-density lipoprotein cholesterol, high triglycerides and cardiovascular disease history. In conclusion, the distribution of CRP in adult Chinese was comparable with that of many other Asian populations but different from that of Western populations. Metabolic impairment was associated with elevated CRP, and CRP levels should be interpreted in conjunction with the lipid profile. Show more

Keywords: C-reactive protein, cardiovascular, risk factors, Chinese

DOI: 10.3233/DMA-2010-0713

Citation: Disease Markers, vol. 28, no. 6, pp. 333-342, 2010

Authors: Chen, Yung-Che | Chang, Huang-Chih | Chen, Chung-Jen | Liu, Shih-Feng | Chin, Chien-Hung | Wu, Chao-Chien | Chao, Tung-Ying | Lie, Chien-Hao | Wang, Chin-Chou | Lin, Meng-Chih

Article Type: Research Article

Abstract: Background and objective: Little is known about the usefulness of lymphocyte subsets as early predictors of anti-tuberculosis (TB) treatment response in immuno-competent patients. Methods: Among a total of 64 patients with culture positive pulmonary TB, 29 remained sputum smear/culture positive or had delayed resolution on CXR (slow responders (SR)), and 35 had sputum culture conversion to negative and rapid resolution on CXR (fast responders (FR)) after two months of anti-tuberculosis treatment. Clinical parameters and …lymphocyte subsets were investigated. Results: A larger proportion of patients in the SR group had cavities on CXR, bilateral lung involvement, positive acid-fast bacilli stains, and complaint of cough at diagnosis than those in the FR group. Absolute counts of CD3^{+} T cells (p = 0.016) and CD8^{+} T cells (p=0.012) at diagnosis were both significantly higher in the SR group. This trend was present throughout the 6-month treatment course. Absolute T cell counts (odds ratio (OR) 1.002, 95% confidence interval (CI) 1.0–1.004), positive sputum acid fast bacilli stain (OR 6.69, 95% CI 1.37–32.77) and bilateral lung involvemment on CXR (OR 13.114, 95% CI 1.87–92.14) at diagnosis were independent predictors for a slow response. Combining these three predictors, a prediction score (PS) could be calculated to display an optimal discrimination for slow response (area under the curve (AUC)=0.855, p < 0.001), whereas absolute T cell counts yielded the highest discriminative value on an individual level (AUC= 0.676, p=0.015). Conclusions: A higher T cell count at diagnosis in patients with TB may predict a slow response to two months of treatment. The calculation of a PS further increased predictive accuracy and performance. Show more

Keywords: Pulmonary tuberculosis, slow responders, absolute T cell counts, prediction score

DOI: 10.3233/DMA-2010-0714

Citation: Disease Markers, vol. 28, no. 6, pp. 343-352, 2010

Authors: Erbilgin, Yucel | Sayitoglu, Muge | Hatirnaz, Ozden | Dogru, Omer | Akcay, Arzu | Tuysuz, Gulen | Celkan, Tiraje | Aydogan, Gonul | Salcioglu, Zafer | Timur, Cetin | Yuksel-Soycan, Lebriz | Ure, Umit | Anak, Sema | Agaoglu, Leyla | Devecioglu, Omer | Yildiz, Inci | Ozbek, Ugur

Article Type: Research Article

Abstract: The NOTCH signaling pathway plays important role in the development of multicellular organisms, as it regulates cell proliferation, survival, and differentiation. In adults, it is essential for the T- or B-lymphocyte lineage commitment. NOTCH1 and FBXW7 mutations both lead the activation of the NOTCH1 pathway and are found in the majority of T-ALL patients. In this study, the mutation analysis of NOTCH1 and FBXW7 genes was performed in 87 pediatric T-ALLs who were treated on the …ALL-BFM protocols. In 19 patients (22%), activating NOTCH1 mutations were observed either in the heterodimerization domain or in the PEST domain and 7 cases (10%) demonstrated FBXW7 mutations (2 cases had both NOTCH1 and FBXW7 mutations). We also analyzed the relationship of the mutation data between the clinical and biological data of the patients. NOTCH1 and FBXW7, NOTCH1 alone were found correlated with lower initial leucocyte counts which was independent from the sex and T- cell immunophenotype. However, NOTCH1 and FBXW7 mutations were not predictive of outcome in the overall cohort of pediatric T-ALLs. Show more

Keywords: T-ALL, NOTCH1, FBXW7, mutation, prognosis

DOI: 10.3233/DMA-2010-0715

Citation: Disease Markers, vol. 28, no. 6, pp. 353-360, 2010

Authors: Ali Hosseini, Seyed | Sobti, Ranbir Chander | Malekzadeh, Kianoosh | Singh, Shrawan Kumar | Joshi, Kusum

Article Type: Research Article

Abstract: Introduction: Amongst the genitourinary cancers, carcinoma of the urinary bladder is one of the leading causes of death in India. Hypermethylation of the CpG islands of gene promoter is one of the earliest and most frequent epigenetic alterations leading to cancer as well as in its development. Several studies have suggested that tumour suppressor genes play a key role in the development of cancer. Methylation in the CDKN2A has been associated with various malignant diseases, but …information with respect to urinary bladder cancer is lacking in north Indian population. Materials and methods: We analyzed the methylation of P16INK4a and P14ARF in 80 tissues and matched blood samples of patients suffering from bladder cancer and 80 blood samples of cancer-free individuals by MS-PCR. Results: In tissue and matched blood samples of bladder cancer patients, the incidence of P14ARF hypermethylation significantly increased (OR=0.31, 95%CI =0.12–0.8, P=0.01) and (OR=0.0, 95%CI=0.0–0.62, P=0.006) respectively with an increase in age. Clinicopathological analysis revealed that P14ARF hypermethylation in tissue and blood samples was significantly associated with invasive stage (⩾ T2) (OR=0.21, 95%CI = 0.08–0.51, P=0.0002) and (OR = 0.09, 95%CI = 0.03–0.37, P= 0.00001) respectively. Muscle invasive tumour stage (⩾T2) showed significant association with increased risk of P16INK4α promoter hypermethylation in tissue and blood samples of patients (OR = 0.38, 95%CI = 0.17–0.82, P= 0.01) and (OR = 0.13, 95%CI = 0.05–0.36, P= 0.00005) respectively. Conclusion: These results suggest that the CpG island hypermethylation status of the defined panel of genes may be a useful biomarker in patients suffering from bladder cancer. Show more

Keywords: Bladder cancer, methylation, tumour suppressor gene, P14ARF, P16INK4a

DOI: 10.3233/DMA-2010-0716

Citation: Disease Markers, vol. 28, no. 6, pp. 361-368, 2010

Authors: Asim, Mohammad | Khan, Luqman A. | Husain, S. A. | Husain, Sajid | Sarma, Manash P. | Ahmad, Istaq | Sharma, J.K. | Sharma, Anita | Sharma, Shashi | Thayumanavan, L. | Kar, P.

Article Type: Research Article

Abstract: Objective: Our aim was to evaluate whether the association of GSTM1/T1 gene polymorphisms modifies the risk of Hepatocellular carcinoma (HCC) and what is its correlation with other predisposing risk factors like alcohol intake, cigarette smoking and hepatitis B and C infections. Study design/setting: It was a case-control study, included 254 HCC cases compared with 525 hospital-based age and sex matched cases of chronic liver disease without HCC as controls from Indian population. The GSTM1 and GSTT1 genotypes …were detected using conventional multiplex PCR method. Results: In this case-control study, we observed a positive correlation between age, HBV and HCV infection, smoking habit of > 20 packs/year, alcohol consumption of > 100 g/day and risk of liver cancer. We found significantly increased risk associated with GSTM1 null genotype (OR = 3.49; 95% CI = 2.52–4.84) as well as GSTT1 null genotype (OR = 3.12; 95% CI = 2.19–4.45), respectively. However, an increased risk of HCC was observed among heavy drinkers with GSTM1 (OR = 2.01; 95% CI = 1.11–3.66). Further, cigarette smoking showed a non-significant association with GSTT1 (OR = 1.49; CI = 0.69–3.25). Conclusion: Our results suggest that the variants in low penetrance gene such as GSTM1 and GSTT1 are associated with an increased liver cancer risk. Further, an influence of GSTM1/T1 null genotypes may contribute in the etiology of HCC in patients with higher cigarette and alcohol consumption. Show more

Keywords: Hepatocellular carcinoma, GSTM1, GSTT1, smokers, alcoholics, polymorphism

DOI: 10.3233/DMA-2010-0717

Citation: Disease Markers, vol. 28, no. 6, pp. 369-376, 2010

Authors: Cherbal, Farid | Bakour, Rabah | Adane, Saida | Boualga, Kada | Benais-Pont, Gaelle | Maillet, Philippe

Article Type: Research Article

Abstract: Background: Breast cancer is the leading cause of cancer death in women in Algeria. The contribution of BRCA1 and BRCA2 mutations to hereditary breast/ovarian cancer in Algerian population is largely unknown. Here, we describe analysis of BRCA1 and BRCA2 genes in 86 individuals from 70 families from an Algerian cohort with a personal and family history suggestive of genetic predisposition to breast cancer. Methods: The approach used is based on BRCA1 and BRCA2 mutations screening …by High-Resolution Melting (HRM) curve analysis followed by direct sequencing. All samples for which no pathogenic mutation was found were analyzed by MLPA for large deletions or duplications. Results: Three distinct pathogenic mutations c.83_84delTG, c.181T>G, c.798_799delTT and two large rearrangements involving deletion of exon 2 and exon 8 respectively, were detected in BRCA1 gene. Moreover 17 unclassified variants and polymorphisms were detected in BRCA1 gene (6 described for the first time). Two pathogenic mutations, c.1310_1313delAAGA and c.5722_5723delCT and 40 unclassified variants and polymorphisms (14 never described before) were identified in BRCA2 gene. Conclusions: For the first time, we used HRM and MLPA to identify BRCA1 and BRCA2 mutations in Algerian patients with a personal and family history suggestive of genetic predisposition to breast cancer. The implications of these new findings in regard to genetic testing and counseling are substantial for the Algerian population. Show more

Keywords: Algeria, BRCA1, BRCA2, hereditary breast cancer, mutation analysis

DOI: 10.3233/DMA-2010-0718

Citation: Disease Markers, vol. 28, no. 6, pp. 377-384, 2010

Authors: Bouanene, Houda | Miled, Abdelhédi

Article Type: Research Article

Abstract: CA125 is a tumor antigen used to monitor the progression and regression of epithelial ovarian cancer. Despite the widespread use of CA125, the biochemical and molecular nature of this antigen is poorly understood. Analysis of the structure of CA125 is essential for determining the physiological role of this very significant tumor marker. Accumulated experimental evidence has shown that CA125 epitopes reside on a molecule of very complex architecture in terms of both protein backbone and oligosaccharide …structures. It is not clear whether the heterogeneity of CA125 molecular characteristics are due to the variability of biological sources from which the molecule was isolated or to the different biophysical methods used for the characterization of all the oligosaccharides linked to CA125 or to the presence of glycoisoforms for this protein. This review attempts to summarize emerging data related to molecular characteristics of CA125 and to compare approaches undertaken to reach a better understanding of molecular features of this tumor marker. Show more

Keywords: CA125 antigen, MUC16, glycosylation

DOI: 10.3233/DMA-2010-0719

Citation: Disease Markers, vol. 28, no. 6, pp. 385-394, 2010