Cancer Biomarkers - Volume 5, issue 4-5

Authors: Hsu, Nan-Yung | Wang, Hwei-Chung | Wang, Chung-Hsing | Chang, Chia-Lin | Chiu, Chang-Fang | Lee, Hong-Zin | Tsai, Chia-Wen | Bau, Da-Tian

Article Type: Research Article

Abstract: Non-homologous end-joining (NHEJ) system is a major route in repairing double strand breaks (DSBs), and is important in maintaining the genome stability. The gene XRCC4 is a central role of the NHEJ system, and it is critical in carcinogenesis. In order to reveal the association between XRCC4 and lung cancer, we recruited 164 lung cancer patients and 649 healthy controls from central Taiwan, investigated seven novel polymorphic variants of XRCC4, includes C-1622T (rs7727691), G-1394T (rs6869366), G-652T (rs2075685), C-571T (rs2075686), intron3 DIP (rs28360071), S247A (rs3734091) and intron7 DIP (rs28360317), and analyzed the association of specific genotype with lung cancer susceptibility. The …results showed that the XRCC4 G-1394T is significant in Taiwanese lung cancer and the GT genotype of G-1394T is an obvious risk factor of lung cancer susceptibility (P=0.0049), and the G allele is a risky factor (P=0.0087). As for XRCC4 C-1622T (rs7727691), G-652T (rs2075685), C-571T (rs2075686), intron3 DIP (rs28360071), S247A (rs3734091) and intron7 DIP (rs28360317) polymorphism sites, there was no difference in the distribution between the lung cancer and control groups. The analyzing results of joint effect for smoking habit and XRCC4 G-1394T polymorphism was that people with GT genotype and smoking habit present the highest risk of lung cancer than other groups (OR=2.31, 95% CI=1.43–3.72). The G allele of the XRCC4 G-1394T may be responsible for lung carcinogenesis and maybe useful in early detection and prevention of lung cancer. Show more

Keywords: XRCC4, polymorphism, lung cancer, carcinogenesis

DOI: 10.3233/CBM-2009-0617

Citation: Cancer Biomarkers, vol. 5, no. 4-5, pp. 159-165, 2009

Authors: Formica, V. | Massara, M.C. | Portarena, I. | Fiaschetti, V. | Grenga, I. | Del Vecchio Blanco, G. | Sileri, P. | Tosetto, L. | Skoulidis, F. | Pallone, F. | Roselli, M.

Article Type: Research Article

Abstract: CEA and CA19.9 are biomarkers routinely measured for monitoring treatment response in metastatic colorectal cancer (MCRC) patients, yet their predictive value during therapies containing new antineoplastic drugs (i.e. FOLFIRI/OLFOX/Bevacizumab) has not yet been investigated. Consecutive chemotherapy-naive MCRC patients treated with either standard chemotherapy-alone (FOLFIRI/FOLFOX) or chemotherapy+bevacizumab (FOLFIRI+bevacizumab) were included in the analysis. Patients had to have serial biweekly measurement of CEA and CA19.9 available for at least three months of treatment. Primary study endpoint was Progression Free Survival (PFS). Biomarker levels and type of treatment as well as major demographic and clinical factors were analyzed for their impact on …PFS. Out of 243 evaluated MCRC patients, 87 had biomarkers available as per inclusion criteria. Among all evaluated factors only type of treatment (chemotherapy-alone vs chemotherapy+bevacizumab) and baseline CA19.9 (> vs < normal) were independently associated with PFS, whilst neither baseline CEA nor biomarker reduction during therapy reached statistical significance. When patients with different baseline CA19.9 levels were analysed separately, only patients with abnormal CA19.9 benefited significantly from the administration of bevacizumab. The current study demonstrated a significant predictive value of CA19.9, but not of CEA and biomarker reduction, for MCRC patients treated with new antineoplastic drugs. Moreover, only patients with abnormal baseline CA19.9 levels benefited significantly from bevacizumab. Show more

Keywords: CEA, CA19.9, bevacizumab, metastatic colorectal cancer patients, irinotecan, oxaliplatin

DOI: 10.3233/CBM-2009-0101

Citation: Cancer Biomarkers, vol. 5, no. 4-5, pp. 167-175, 2009

Authors: Lee, Gregory | Ge, Bixia

Article Type: Research Article

Abstract: OC-3-VGH ovarian cancer cell line and numerous others from different human tissue origins were studied for their respective expressions of immunoglobulins as well as carbohydrate-associated epitope(s) recognized by RP215 monoclonal antibody. With no exceptions, all the cancer cell lines studied so far express human immunoglobulin G (IgG) heavy chains when determined by Western blot or nested RT-PCR with appropriate primers in the constant region. By Western blot assay, it was also shown that greater than 90% of cancer cell lines expressed RP215-specific epitope(s) on the detected heavy chain molecules. Further studies with OC-3-VGH cancer cells revealed the expressions of all …immunoglobulin classes, subclasses, heavy as well as light chains. The primary structure of the IgG heavy chains expressed by single cloned cells of this cancer cell line was elucidated. It was shown to be homologous to that of normal human IgG1 heavy chain derived from B cells, except with high content of serine/threonine residues in the variable region. Expressions of other immunoglobulin-related genes were also detected. Widespread expressions of immunoglobulin heavy chains among cancer cells as well as the frequent presence of unique carbohydrate-associated epitope(s) recognized by RP215 monoclonal antibody might have important biological implications during carcinogenesis and applications in immunodiagnostics and antibody-based anti-cancer drug developments. Show more

Keywords: CA215, pan cancer biomarker, Immunoglobulins, RT-PCR, carbohydrate-associated epitope, RP215 monoclonal antibod

DOI: 10.3233/CBM-2009-0102

Citation: Cancer Biomarkers, vol. 5, no. 4-5, pp. 177-188, 2009

Authors: Sainger, Rachana N. | Shah, Franky D. | Telang, Shaila D. | Shah, Pankaj M. | Patel, Prabhudas S.

Article Type: Research Article

Abstract: Telomere attrition is an important event during tumorigenesis regulated by factors including oxidative stress, mitochondrial function, DNA adducts etc. Critically short telomeres act as signal for telomerase activity in the cancer cells. To determine whether null genotype of GSTM1 gene has any association with telomere length shortening and telomerase activity, we analyzed telomere length, telomerase activity and GSTM1 polymorphism in oral tissues. We observed that malignant tissues exhibited shorter telomere length. Telomerase activity was observed in about 75% malignant tissues. 40% of the oral cancer patients exhibited GSTM1 polymorphism. Further, shorter telomere lengths were observed in patients having GSTM1 polymorphism. …Also, the GSTM1 genotype showed negative correlation with telomerase activity and telomere length. Our study proposes role of GSTM1 polymorphism in telomere attrition and subsequent telomerase activity in the cancer cells. The results are suggestive of possible link between absence of GSTM1 gene and telomere length alterations. Show more

Keywords: Telomere attrition, telomerase activity, GSTM1 polymorphism, oral cancer

DOI: 10.3233/CBM-2009-0103

Citation: Cancer Biomarkers, vol. 5, no. 4-5, pp. 189-195, 2009

Authors: Sunde, Lone | Bisgaard, Marie Luise | Soll-Johanning, Helle | Jacobsen, Niels Otto | Bolund, Lars | Skouv, Jan | Lynge, Elsebeth

Article Type: Research Article

Abstract: Colonoscopy is recommended for persons with a familial risk of colorectal cancer (CRC). A familial risk is identified by a family history with CRC and/or predisposing mutation(s). However, such information may not be available. We analysed whether MSI (MicroSatellite Instability) and/or CIN (Chromosome INstability=LOH (loss of heterozygosity) and/or DNA-aneuploidy (abnormal nuclear DNA contents)) could be used as predictors of familial CRC. Formalin-fixed tissue from 97 patients with CRC (29 patients with 2 or more affected first-degree relatives (="cases"), 29 matched CRC controls without a family history, and 39 relatives to cases) were analysed for MSI and CIN. …In this small case-control study, no significant differences in the frequencies of MSI and CIN were observed between cases with a family history and their controls without a family history. MSI+;CIN- was observed in 6/29 cases and in 0/29 controls (p=0.02), most frequently in cases with affected siblings, only (3/7). However, for 13 patients from whom several CRC tumours were analysed, concordant results for MSI/LOH/DNA-ploidy were obtained only in 10/9/9. Among cases and relative(s), concordant results for MSI, LOH and DNA-ploidy were obtained in 16/26, 16/26, and 14/25 families, respectively. Although MSI+;CIN- appeared to predict familial CRC with a high specificity, neither MSI, CIN, or MSI+;CIN- are likely to be sufficiently sensitive predictors of familial CRC. Show more

Keywords: Chromosomal instability (CIN), DNA-ploidy, familial colorectal neoplasms, Loss of heterozygosity (LOH), Microsatellite instability (MSI), flow fluorometry

DOI: 10.3233/CBM-2009-0104

Citation: Cancer Biomarkers, vol. 5, no. 4-5, pp. 197-205, 2009

Authors: Bhavani, V. | Srinivasulu, M. | Ahuja, Y.R. | Hasan, Q.

Article Type: Research Article

Abstract: The pattern of altered gene expression due to epigenetic change is of major importance in malignancies. Aberrant DNA methylation is one of the many potential causes for this and is considered to be an early event in the etiology of breast carcinogenesis. The present study assessed the methylation status of three genes relevant in breast cancer (BC): The breast cancer susceptibility gene 1 (BRCA1), 17 beta hydroxy steroid dehydrogenase type 1 (HSD17B1) and type 2 (HSD17B2). Restriction enzyme based Methylation specific PCR (REMS PCR) was carried out in 104 tumor samples from sporadic BC patients and 48 samples …of adjacent normal breast tissue. The percentage of tumor samples showing BRCA1, HSD17B1 and HSD17B2 methylation was 20.4%, 83.3% and 31.3%, respectively. Methylation was higher in tumors when compared to adjacent normal breast tissue samples. This suggests that methylation of these three genes plays an important role in BC etiology. Methylation is responsible for gene silencing and since BRCA1 and HSD17B2 were not found to be methylated in the same tissue samples, this suggests that the etiology of > 50% of the tumors could be accounted for by the independent epigenetic silencing of these two genes. BRCA1 and HSD17B2 genes may increase the risk of developing BC via enhanced estradiol activity. It is for the first time that the role of HSD17B gene methylation in BC pathophysiology is being proposed.methylation in BC pathophysiology is being proposed. Show more

Keywords: Breast cancer, BRCA1, estrogen, HSD17Bs, Methylation

DOI: 10.3233/CBM-2009-0105

Citation: Cancer Biomarkers, vol. 5, no. 4-5, pp. 207-213, 2009

Authors: Yoon, Nam K. | Seligson, David B. | Chia, David | Elshimali, Yahya | Sulur, Giri | Li, Ai | Horvath, Steve | Maresh, Erin | Mah, Vei | Bose, Shikha | Bonavida, Benjamin | Goodglick, Lee

Article Type: Research Article

Abstract: The protein 14-3-3σ is involved in the regulation of cellular processes such as apoptosis, cell cycle progression and proliferation. Disruption of protein expression has been implicated in a number of malignancies. Here we examine the expression pattern of 14-3-3σ in breast cancer and specifically consider whether expression in ductal carcinoma in situ (DCIS) lesions is predictive of disease outcome. We examined 14-3-3σ protein expression and localization using immunohistochemical staining on a high-density tissue microarray consisting of 157 invasive breast cancer patients. Statistical analyses were used to assess the correlation of 14-3-3σ expression with clinico-pathological parameters and patient outcome. We observed …a statistically significant increase in 14-3-3σ protein expression in ductal hyperplasia, DCIS, and invasive ductal carcinoma (IDC) as compared normal glandular epithelium. In IDC, lower expression of 14-3-3σ tended to predicted poorer survival time while in DCIS lesions, there was a stronger correlation between relatively higher levels of 14-3-3σ predicting shorter survival time. Further, of patients who had concurrent DCIS and IDC lesions, those that exhibited a decrease of 14-3-3σ expression from DCIS to IDC had significantly shorter survival time. Our findings indicate that 14-3-3σ expression may be a useful prognostic indicator for survival in patients with breast cancer with an elevated 14-3-3σ in earlier disease predicting a less favorable disease outcome. To our knowledge this is the first published study associating 14-3-3σ protein expression with breast cancer survival. Show more

Keywords: Tissue microarray, breast cancer, tumor marker, 14-3-3σ, prognostic marker, DCIS

DOI: 10.3233/CBM-2009-0106

Citation: Cancer Biomarkers, vol. 5, no. 4-5, pp. 215-224, 2009

Authors: González-Andrade, Fabricio | Sánchez, Dora

Article Type: Research Article

Abstract: Background: Limited data are available describing human papilloma virus (HPV) genotype distributions in gynecological lesions in Ecuador. To predict how HPV vaccination and HPV-based screening will influence cervical cancer prevention it needs such studies. Methods: We analyzed 124 samples from women, adults between 18 to 55 years old, Mestizas (Hispanics), were born and living in Quito, Ecuador. They showed an atypical sample in PapTest or a histological abnormal evaluation. We used the kit PVH Fast® 2.0 with conventional PCR to study cervical and vulvar swabs prior colposcopy and/or cytology. Results and conclusions: We found 23 different …genotypes. 84/104 cases were positive for HPV (67.7%); 32/124 cases were negative (25.8%); and, in 8/124 cases (6.5%) we were unable to ascertain the existence or lack of HPV. The most common viral genotype was 6 (8.8%) followed by the 66 (4.8%) and 16, 31, 44 types (2.4% each one). Types 11, 34, 35, 54, 59, 62 and 67 showed a frequency equivalent to 1.6% each one. The remaining types showed a 0.8% frequency. Most common high-risk genotypes were 16 and 31, low-risk 6 and 41 and, the third most common group HPV type detected in this cohort was HPV 66. HPV 6 showed the highest prevalence. HPV 66 was associated with atypical cytology and was found in women with borderline cytology, low-grade lesions and high-grade lesions, but was most frequent in the threshold group. We examine a case of coexistence of 2 genotypes together 51 and 58. We found very low prevalence of HPV18 alone or HPV16/18. In 25 samples, 20.16% (25/124) we found HPV presence but we were unable to identify the genotype. We need more studies with a broad sampling to complete our geographic pattern of HPV distribution. Show more

Keywords: HPV, PCR, Quito, Ecuador, genotyping, cervical cancer , risk factor, screening, prevalence

DOI: 10.3233/CBM-2009-0107

Citation: Cancer Biomarkers, vol. 5, no. 4-5, pp. 225-232, 2009