• Asian Pacific Journal of Cancer Prevention
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• v.17 no.3
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• pp.1015-1018
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• 2016

Background: Overexpression or amplification of human epidermal growth factor receptor-2 (HER2) is associated with grade of malignancy and a poor prognosis in breast cancer (BC). The aim of this study was to evaluate of value of HER2 as a prognostic marker, and to analyze associations with common histopathological parameters in BC cases. Materials and Methods: Between of 2007 to 2014, 260 patients with BC referred to Oncology Clinic provided cancer tissue samples which underwent immunohistochemistry (IHC) for markers. ER and PR positivity was defined as ${\geq}10%$ positive tumor cells with nuclear staining. HER2-positive was defined as either HER2 gene amplification by fluorescent in situ hybridization (FISH) or scored as 3+ by IHC. For HER2 (2+), FISH was performed to determine HER2 positivity. Results: The mean age at diagnosis for the patients with HER2-negative was significantly higher than in HER2-positive cases. Also, there were significant correlations between histological grade, nuclear grade, lymph node metastasis, tumor size, ER status, PR status, p53 overexpression and Ki-67 index with HER2 expression. HER2-negative lesions were of higher grade and more likely to be ER-negative, PR-negative, p53-positive, lymph node metastasis, with a tumor size<2cm and also $Ki-67{\geq}20%$ as compared to the HER2-positive group. Conclusions: Contrary to the results of other studies, HER2-positive tumors in our study had a lower Ki-67 index and were p53-positive. Also, Ki-67 proliferation index ${\geq}20%$ in more studies was associated with p53-positive.Therefore, tumors which are HER2-positive and have a Ki-$67{\geq}20%$ had a more aggressive behavior compared to HER2-positive and Ki-67<20% lesions.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.12
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• pp.6207-6210
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• 2012

Introduction: Although a number of studies were published in the past several years on associations between hsa-mir-27a and cancer risk, the findings remain conflicting rather than conclusive. To derive a more precise effect on the association between SNP hsa-mir-27a rs895819 and breast cancer risk, we conducted a meta-analysis for the first time. Materials and Methods: Through retrieval from PubMed for the period up to August 2012, a total of four studies were identified with 3,287 cases and 4,298 controls for SNP hsa-mir-27a rs895819. We calculated summary odds ratio (ORs) and corresponding 95% confidence intervals (CIs) using a fixed effects model (when the heterogeneity was absent, P>0.10). Otherwise, the random-effects model was used. Results: We found that hsa-mir-27a rs895819 polymorphism also did not reveal any relationship with breast cancer susceptibility (AG versus AA: OR = 0.98; 95%CI, 0.73-1.32; GG versus AA: OR = 0.86; 95% CI, 0.72-1.03; AG/GG versus AA: OR = 0.92; 95% CI, 0.74-1.14), while significantly decreased risk was found among Europeans in AG versus AA and AG/GG versus AA models tested (AG versus AA: OR = 0.83; 95%CI, 0.72-0.97; GG versus AA: OR = 0.86; 95% CI, 0.71-1.05; AG/GG versus AA: OR = 0.84; 95% CI, 0.75-0.94). Conclusion: These findings suggest that hsa-mir-27a rs895819 polymorphism may play an important role in breast cancer development.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.11
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• pp.7007-7010
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• 2013

Background: In the literature, data concerning the relationship between breast cancer and HLA class II gene polymorphisms are limited, so the aim of this study was to determine if HLA-DQB1 and HLA-DRB1 MHC class-II alleles may confer susceptibility or resistance to the disease among Jordanian females. Materials and Methods: This case control study enrolled 56 Royal Hospital breast cancer patients and 60 age matched healthy controls, all of whom provided blood samples (2011-2013). A questionnaire was filled after signing a consent form and DNA was extracted, nucleic acids being amplified for assessment of HLA-DQB1 and HLA-DRB1 alleles by muliplex INNO-LiPA and allele typing carried out by reverse hybridization. Comparison of HLA-DQB1 and HLA-DRB1 allele distributions was carried out with paired t-test and chi-square statistics. Risk factors were assessed by odd ratios with 95% confidence intervals. Results: A significant negative correlation was observed between $HLADQB1^*$ 02 alleles and breast cancers (p=0.013). No significant associations were observed among $HLADQB1^*$ 03, 04, 05 and 06 or among $HLA-DRB1^*$ 01, 03, 04, 07, 08, 10, 11, 13, 14 and 15. Conclusions: $HLADQB1^*$ 02 alleles may provide positive protection against breast tumor risk among Jordanians, but not $HLADQB1^*$ 03, 04, 05 and 06 or $HLA-DRB1^*$ 01, 03, 04, 07, 08, 10, 11, 13, 14 and 15 alleles.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.11
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• pp.6703-6707
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• 2013

Background: Numerous epidemiological studies have been conducted to evaluate the association between variants of the DNA repair gene XRCC3 and cancer risk. Here we focused on one XRCC3 polymorphism and development of cervical cancer, performing a meta-analysis. Methods: The pooled association between the XRCC3 Thr241Met polymorphism and cervical cancer risk was assessed by odds ratios (ORs) and their 95% confidence intervals (95%CIs). Results: A total of 5 case-control studies met the inclusion criteria. The pooled ORs for the total included studies showed no association among homozygotes TT vs. CC: OR=1.93, 95%CI=0.68-5.49, P=0.22; dominant model TT+TC vs. CC: OR=1.37, 95%CI=0.90-2.06, P=0.14; and recessive model TT vs. TC+CC: OR=1.76, 95%CI=0.68-4.55, P=0.25, but might be a slight risk factor for cervical cancer in heterozygote contrast TT vs. CT: OR= 1.33, 95%CI=1.04-1.71, P=0.02. In subgroup analysis, significant associations were found for Asians under all genetic models. Conclusions: Our meta-analysis suggested the XRCC3 Thr241Met polymorphism might not act as a cervical cancer risk factor overall. However, in subgroup analysis, a significant association was found in Asians under all genetic models. The association should be studied with a larger, stratified population, especially for Asians.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.7
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• pp.3247-3252
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• 2012

Aim: We conducted a prospective study in an Chinese population to detect associations of GSTM, GSTT and GSTP polymorphisms with hepatocellular carcinoma (HCC), and analyze roles in determining survival outcome. Methods: A prospective follow-up study was conducted with 476 HCC patients and 481 controls collected from May 2005 to May 2007. All patients were followed up until the end of Dec. 2011. GSTM1, GSTT1 and GSTP1 genotyping were performed by PCR-CTPP methods. Results: Null GSTM1 carriers had a 1.64 fold risk of HCC compared with non-null genotype, while GSTP1 Val/Val carriers had a 93% increased risk over the GSTP1 IIe/IIe genotype. The median follow-up time for the 476 patients was 34.2 months (range: 1 to 78 months). Individuals with null GSTM1 genotype had better survival of HCC than non-null genotype carriers (HR=0.71, 95%CI=0.45-0.95). Similarly, GSTP1 Val/Val genotypes had significant better survival than the GSTP1 IIe/IIe genotype (HR=0.34, 95%CI=0.18-0.65). Individuals carrying null GSTM1 and GSTP1 Val/Val who received chemotherapy had lower risk of death from HCC than those without chemotherapy. Conclusion: This study indicated carriage of null GSTM1 and GSTP1 Val/Val genotypes to have roles in susceptibility to and survival from HCC.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.8
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• pp.3805-3809
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• 2014

Background: In Mexico, breast cancer (BCa) is the leading type of cancer in women. Cytochrome P450 (CYP450) is a superfamily of major oxidative enzymes that metabolize carcinogens and many antineoplastic drugs. In addition, these enzymes have influence on tumor development and tumor response to therapy. In this report, we analyzed the protein expression in patients with BCa and in healthy women. Links with some clinic-pathological characteristic were also assessed. Materials and Methods: Immunohistochemical analyses were conducted on 48 sets of human breast tumors and normal breast tissues enrolled in Hospital Militar de Especialidades de la Mujer y Neonatologia and Hospital Central Militar, respectively, during the time period from 2010 to 2011. Informed consent was obtained from all participants. Statistical analysis was performed using ${\chi}^2$ or Fisher exact tests to estimate associations and the Mann Whitney U test for comparison of group means. Results: We found a significant CYP3A4 overexpression in BCa stroma and gland regions in comparison with healthy tissue. A significant association between protein expression with smoking, alcoholism and hormonal contraceptives use was also observed. Additionally, we observed estrogen receptor (ER) and progesterone receptor (PR) positive association in BCa. Conclusions: We suggest that CYP3A4 expression promotes BCa development and can be used in the prediction of tumor response to different treatments. One therapeutic approach may thus be to block CYP3A4 function.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.sup3
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• pp.71-75
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• 2016

Pancreatic cancer is a leading cause of fatality worldwide. Several population studies have been conducted on genetic diagnosis of pancreatic cancer but the results from epidemiologic studies are very limited. CYP17A gene has a role in disease formation but its influence on pancreatic cancer is unclear. A polymorphism in the 5'UTR promoter region of CYP17A1-34T/C (A1/A2) has been associated with multiple cancers. The aim of the current study was to assess associations of this polymorphism and socio-demographic risk factors with pancreatic cancer. A total of 255 and 320 controls were enrolled in the study, and were genetically analyzed through PCR-RFLP. Statistical analysis was conducted with observed genotype frequencies and odds ratios (ORs) and 95% CIs were estimated using unconditional logistic regression. The impact of socio-demographic factors was accessed through Kaplen-Meir analysis. According to our results, the A2/A2 genotype was significantly associated with pancreatic cancer (OR=2.1, 95%CI = 1.3-3.5). Gender female (OR=2.6, 95%CI=1.8-3.7), age group 80s/80+ years (OR=2.2, 95% CI=1.2-4), smoking both former (OR=4.6, 95% CIs=2.5-8.8) and current (OR=3.6, 95% CI=2-6.7), and family history (OR=7.1; 95%CI = 4.6-11.4) were also found associated with increased risk. Current study suggests that along with established risk factors for pancreatic cancer CYP17A1-34T/C may play a role. However, on the basis of small sample size the argument cannot be fully endorsed and larger scale studies are recommended.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.12
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• pp.5195-5201
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• 2016

Background: Brain tumors, constituting one of the most deadly forms of cancer worldwide, result from the accumulation of multiple genetic and epigenetic alterations in genes and signaling pathways. Isocitrate dehydrogenase enzyme isoform 1 (IDH1) mutations are frequently identified in primary brain tumors and acute myeloid leukemia. Studies on IDH1 gene mutations have been extensively performed in various populations worldwide but not in Malaysia. This work was conducted to study the prevalence of IDH1 c.395G>A (R132H) hotspot mutations in a group of Malaysian patients with brain tumors in order to gain local data for the IDH1 mutation profile in our population. Methods: Mutation analysis of c.395G>A (R132H) of IDH1 was performed in 40 brain tumor specimens by the polymerase chain reaction-restriction fragment length polymorphism method (PCR-RFLP) and then verified by direct sequencing. Associations between the IDH1 c.395G>A (R132H) mutation and clinicopathologic characteristics were also analyzed. Results: The IDH1 c.395G>A (R132H) mutation was detected in 14/40 patients (35%). A significant association was found with histological tumor types, but not with age, gender and race. Conclusions: IDH1 is frequently mutated and associated with histological subtypes in Malay brain tumors.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.5
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• pp.2319-2324
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• 2012

Aim: To investigate the expression of three components of the Hedgehog (Hh) signaling pathway (SHH, SMO and GLI1) in human colorectal cancer (CRC) tissues and evaluate their association with clinicopathologic characteristics of the patients. Methods: Fresh tumor tissues and matched tissues adjacent to the tumor were collected from 43 CRC patients undergoing surgery. Normal colorectal tissues from 20 non-CRC cases were also sampled as normal controls. The expression of SHH, SMO, GLI1 mRNAs was assessed by RT-PCR and proteins were detected by immunohistochemical staining. Associations with clinicopathological characteristics of patients were analyzed. Results: SHH mRNA was expressed more frequently in tumor tissues than in normal tissues, but the difference did not reach significance in comparison to that in the adjacent tissues. SMO and GLI1 mRNAs were expressed more frequently in tumor tissues than in both adjacent andnormal tissues. The expression intensities of SHH, SMO, GLI1 mRNA in tumor tissues were significantly higher than those in adjacent tissues and normal tissues. Proteins were also detected more frequently in tumors than other tissues. No significant links were apparent with gender, age, location, degree of infiltration or Dukes stage. Conclusion: Positive rates and intensities of mRNA and protein expression of Hh signaling pathway related genes SHH, SMO, GLI1 were found to be significantly increased in CRC tissues. However, over-expression did not appear to be associated with particular clinicopathological characteristics.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.10
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• pp.5251-5255
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• 2012

Background and Aim: Although the functional consequences of MDR-1 polymorphisms have been the subject of numerous studies, to the best to our knowledge, associations with clinical side effects of anticancer drugs have yet to be assessed. Our aim was to clarify any role of the C3435T polymorphism of the MDR1 gene in oral mucositis and its relation with elevated reactive oxygen species (ROS) levels, in children with acute lymphoblastic leukemia (ALL). Materials and Methods: The distribution of the MDR-1 C3435T polymorphism in 47 patients with ALL was determined by RFLP and compared with that of 68 healthy controls. Results: There were no association in distribution of genotypes of MDR-1 C3435T polymorphism and the risk of ALL. Oral mucositis were detected in 78.7% (n=37) of the patients and significantly related to the MDR-1 CT genotype (p=0.042), as confirmed by logistic regression analysis. Conclusion: Our preliminary data suggest that children carrying the CT genotype are more prone to develop oral mucositis, which might mean that the heterozygous genotype leads to accumulation of more reactive oxygen species. Since a limited number of patients was investigated, further studies are needed to confirm these findings.