Association of RAD 51 135 G/C, 172 G/T and XRCC3 Thr241Met Gene Polymorphisms with Increased Risk of Head and Neck Cancer

Kayani, Mahmood Akhtar,Khan, Sumeera,Baig, Ruqia Mehmood,Mahjabeen, Ishrat Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.23

Homologous recombination repair (HRR) plays an important role in protection against carcinogenic factors. Genes regulating the HRR mechanisms may impair their functions and consequently result in increased cancer susceptibility. RAD 51 and XRCC3 are key regulators of the HRR pathway and genetic variability in these may contribute to the appearance and progression of various cancers including head and neck cancer (HNC). The aim of the present study was to compare the distribution of genotypes of RAD51 (135G/C, 172 G/T) and XRCC3 (Thr241Met) polymorphisms between HNC patients and controls. Each polymorphism was genotyped using the polymerase chain reaction-restriction fragment length polymerase (PCR-RFLP) technique in 200 pathologically confirmed HNC patients along with 150 blood samples from normal, disease free healthy individuals. We observed that homozygous variant CC genotype of RAD51 135G/C was associated with a 2.5 fold increased HNC risk (OR=2.5; 95%CI=0.69-9.53; p<0.02), while second polymorphism of RAD 51 172 G/T, heterozygous variant GT genotype was associated with a 1.68 fold (OR=1.68; 95%CI=1.08-2.61; p<0.02) elevation when compared with controls. In the case of the Thr241Met polymorphism of XRCC3, we observed a 16 fold (OR=16; 95% CI=3.78-69.67; p<0.0002) increased HNC risk in patients compared to controls. These results further suggested that RAD51 (135G/C, 172 G/T) and XRCC3 (Thr241Met) polymorphisms may be effective biomarkers for genetic susceptibility to HNC. Larger studies are needed to confirm our findings and identify the underlying mechanisms.

Hepatitis B Screening before Chemotherapy

( Farhana Kayani ),( Amna Subhan Butt ) 대한간학회 2017 춘·추계 학술대회 (KASL) Vol.2017 No.1

Aims: Hepatitis B virus (HBV) and Hepatitis C virus ( HCV) infection, a major health burden that affects approximately 350 million and 140 million people worldwide. Hepatitis B and C reactivation are potentially serious complication of anticancer chemotherapy, which occurs during and after therapy causing increased mortality and morbidity. Reactivation has been reported most frequently in patients with hematologic malignancies, but it has also been associated with chemotherapy use in patients with solid tumors. Screening patients before the initiation of immunosuppressive treatment is therefore important so that prophylaxis can be commenced to prevent HBV and HCV reactivation. Objective of the study is to determine the frequency of cancer patients undergoing screening for hepatitis B and C before start of chemotherapy. Methods: Cross sectional study was conducted.Data was collected from early January 2011 till late December 16. 400 diagnosed cancer patients who met the diagnostic criteria were included. Demographic data was presented as simple descriptive statistics giving mean and standard deviation and qualitative variables was presented as frequency and percentages. Effect modifiers were controlled through stratification. Post stratification chi square test was applied taking p-value of ≤0.05 as significant.Cross sectional study was conducted.Data was collected from early January 2011 till late December 16. 400 diagnosed cancer patients who met the diagnostic criteria were included. Demographic data was presented as simple descriptive statistics giving mean and standard deviation and qualitative variables was presented as frequency and percentages. Effect modifiers were controlled through stratification. Post stratification chi square test was applied taking p-value of ≤0.05 as significant. Results: A total of 400 diagnosed cancer patients were included in this study. Mean age in our study was 55.10±8.39 years. 60 (40.8) were male and 87 (59.2%) were female. Out of 400 cancer patients, 169 (42.25%) and 231 (57.75%) patients were screened and not screened for Hepatitis B and C respectively. Conclusions: Screening of HBV and HCV infection should be suggested as a routine investigation in cancer patients before receiving chemotherapy for timely detection and prevention of reactivation of HBV and HCV infection causing fatal complications and mortality associated with it.

Effect of Cooling Rate on Precipitation Behavior of Al–7.65Zn–2.59Mg–1.95Cu Alloy with Minor Elements of Zr and Ti

Saif Haider Kayani,Jae‑Gil Jung,Min‑Seok Kim,Kwangjun Euh 대한금속·재료학회 2020 METALS AND MATERIALS International Vol.26 No.7

We investigate the effect of cooling rate on the precipitation behavior during cooling from solution treatment temperatureand post-aging of a high-strength Al–7.65Zn–2.59Mg–1.95Cu–0.11Zr–0.04Ti extruded alloy. Solution treatment at 450 °Ccaused the partial dissolution and disintegration of η phase, along with a partial recrystallization of Al grains. The formationof fine L12-type Al3Zr/Al3(Zr,Ti) (~ 20 nm) and relatively large Ti-rich dispersoids (~ 100 nm) took place during extrusionand/or solution treatment processes. The slow cooling from solution treatment temperature (0.3 °C/min) caused theprecipitation of η phases on coarse Al3(Zr,Ti) particles (formed during solidification), Ti-rich dispersoids (formed duringextrusion/solution treatment), grain boundaries, and grain interiors, thereby resulting in negligible aging responses duringpost-aging at room and elevated temperatures. During fast cooling at 850 °C/min, however, the η phases did not precipitateand thus the Al matrix remained supersaturated, leading to significant aging responses by the formation of GP zones andmetastable η″/η′ precipitates.

적층제조한 Inconel 718 합금의 미세조직이 인장 거동에 미치는 영향

세프카야니(S. Kayani),박상은(S. Park),정임두(I. D. Jung),김정기(J. G. Kim),설재복(J. B. Seol),성효경(H. Sung) 한국기계가공학회 2021 한국기계가공학회 춘추계학술대회 논문집 Vol.2021 No.12

Genetic Deletions of GSTM1 and GSTT1 in Head and Neck Cancer: Review of the Literature from 2000 to 2012

Masood, Nosheen,Yasmin, Azra,Kayani, Mahmood A. Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.6

Head and neck cancer is one of the leading causes of deaths worldwide. Two genes GSTM1 and GSTT1 involved in phase II of carcinogen detoxification have been frequently studied in the literature. Their null genotypes are thought to be associated with increased head and neck cancer risk. However, the published reviews are not up to date and many important papers have been skipped. The current literature review was restricted to the null genotypes of the GSTM1 and GSTT1 genes with special emphasis on the genotypic status. We found that the size of study sample varied greatly and the oral cavity cancer was more influenced by GSTM1 and GSTT1 gene deletions. With respect to ethnicity Asians are more prone to head and neck cancers with these null genotypes as compared to Europeans and Americans. The current review showed significant associations (OR=9.0, 95%CI; 1.4-9.5; OR=3.7, 95%CI; 1.4-9.5) of GSTM1 and GSTT1 null genotypes with head and neck cancers. Review confirms the data of previous reviews that GSTM1 and GSTT1 gene polymorphisms may be risk factors for cancer initiation.

Association of SYK Genetic Variations with Breast Cancer Pathogenesis

Shakeel, Shafaq,Mahjabeen, Ishrat,Kayani, Mahmood Akhtar,Faryal, Rani Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.5

Spleen tyrosine kinase (SYK) is a non-receptor type cytoplasmic protein and a known tumor suppressor gene in breast cancer. Polymorphisms in SYK have been reported to be associated with cell invasion/cell morality and an increased risk of cancer development. In this case control study, all exons of the SYK gene and its exon/ intron boundaries were amplified in 200 breast cancer cases and 100 matched controls and then analyzed by single stranded conformational polymorphism. Amplified products showing altered mobility patterns were sequenced and analyzed. Twelve variations were identified in exonic and intronic regions of DNA encoding SH2 domain and kinase domain of the SYK gene. All of these mutations are novel. Among them, 5 missense mutations were observed in exon 15 while one missense mutation was found in exon 8. In addition to these mutations, six mutations were also identified in intronic regions. We found a significant association between SYK mutations and breast cancer and observed that Glu241Arg, a missense mutation is associated with an increase risk of ~7 fold (OR=6.7, 95% CI=1.54-28.8), Thr581Pro (missense mutation) is associated with increased risk of ~16 fold (OR=15.5, 95%CI=2.07-115.45) and 63367 T>G (missense mutation) is associated with increased risk of ~13 fold (OR=12.8, 95%CI=1.71-96.71) for breast cancer. Significant associations were observed for each of these variations with both late menopause (p<0.01) and early menarche (p<0.005) cases when compared to controls. Our findings suggest that the polymorphic gene SYK may contribute to the development of breast cancer in at least the Pakistani population. This study provides an insight view of SYK which may provide a significant finding for the pharmaceutical and biotechnology industry.

Mutational Analysis of the MTHFR Gene in Breast Cancer Patients of Pakistani Population

Akram, Muhammad,Malik, Fa,Kayani, Mahmood Akhtar Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.4

Objectives: Since methylenetetrahydrofolate reductase (MTHFR) maintains the balance of circulating folate and methionine and blocks the formation of homocysteine, its regulation in relation to different cancers has extensively been studied in different populations. However, information on Pakistani breast cancer patients is lacking. The MTHFR gene has two most common mutations that are single nucleotide additions which result in change of amino acids C677T to Ala222val and A1298C to Glu429Ala. Methodology: 110 sporadic breast patients with no prior family history of cancer or any other type of genetic disorders along with 110 normal individuals were screened for mutations in exons 1 to exon 9 using single strand conformational polymorphism, RFLP and sequencing analyzer. Results: The p values for the 677CC, 677CT, and 677TT genotypes were 0.223, 0.006, and 0.077, respectively. Those for the 1298AA, 1298AC, and 1298CC genotypes were 0.555, 0.009, and 0.003, respectively. Conclusions: We found an overall a significant, weak inverse association between breast cancer risk and the 677TT genotype and an inverse association with the 1298C variant. These results for MTHFR polymorphism might be population specific in sporadic breast cancer affected patients but many other factors need to be excluded before making final conclusions including folate intake, population and disease heterogeneity.

Unusual Intronic Variant in GSTP1 in Head and Neck Cancer in Pakistan

Masood, Nosheen,Malik, Faraz Arshad,Kayani, Mahmood Akhtar Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.4

In the present case control study mRNA expression of the GSTP1 gene, encoding a phase II enzyme that detoxifies via glutathione conjugation, was investigated using semiquantitative PCR followed by SSCP for 49 confirmed head and neck (HN) cancer and 49 control samples. It was found that GSTP1 was upregulated in significantly higher number of cancers (OR 4.2, 95% CI 1.2-15.3). Grade wise correlation was also observed with more up regulation in patients with more advanced grades of HN carcinomas. We also found that 5 patients showed variation in mRNA with a larger product size than expected. Sequencing revealed insertion of an intronic segment between the $6^{th}$ and $7^{th}$ exon of the GSTP1 gene. Germline screening was performed showing mobility shifts which suggested mutation at the DNA level resulting in intronic portion retention. This study is of prime importance for drug design and treatment selection to overcome increased resistance of HN cancers to drugs due to alteration in the GSTP1 gene.

Correlation between Selected XRCC2, XRCC3 and RAD51 Gene Polymorphisms and Primary Breast Cancer in Women in Pakistan

Qureshi, Z.,Mahjabeen, I.,Baig, R.M.,Kayani, M.A. Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.23

Genetic polymorphisms in homologous recombination repair genes cause an abnormal development of cancerous cells. In the present study we evaluated the possibility of breast cancer association with single nucleotide polymorphisms of RAD51, XRCC2 and XRCC3 genes. Polymorphisms selected in this study were RAD51 135G/C, XRCC2 Arg188His; and XRCC3 Thr241Met. Each polymorphism was genotyped using Polymerase chain reaction-restriction fragment length polymorphism in study cohort of 306 females (156 breast cancer patients and 150 controls). We observed that heterozygous variant genotype (GC) of RAD51 135 G/C polymorphism was associated with a significantly (OR=2.70; 95%CI (0.63-1.79); p<0.03) increased risk of breast cancer. In case of the XRCC3 gene we observed that frequency of heterozygous (OR=2.88; 95%CI (1.02-8.14); p<0.02) and homozygous (OR=1.46; 95%CI (0.89-2.40); p<0.04) genotype of Thr241Met polymorphism were significantly higher in breast cancer patients. For the Arg188His polymorphism of XRCC2, ~2fold increase in breast cancer risk (OR=1.6, 95%CI = 0.73-3.50) was associated with GA genotype with a p value for trend of 0.03. Our results suggest that the 135G/C polymorphism of the RAD51, Thr241Met polymorphism of XRCC3 and Arg188His polymorphism of XRCC2 can be independent markers of breast cancer risk in Pakistan.

Acetylation of Retinoblastoma Like Protein2 (Rb2/p130) in Tumor Tissues

Khan, Z.N.,Sabir, M.,Kayani, M.A.,Saeed, M. Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.4

The activity of Rb proteins is controlled by post-translational modifications, especially through phosphorylation. Acetylation of Rb2/p130 was reported recently in NIH3T3 cells but its physiological relevance in cell cycle control and tumorigenesis is still unknown. Efforts are underway to investigate possible interplay between Rb2/p130 phosphorylation and acetylation. Here we hypothesized that Rb2/p130 acetylation, like p53 acetylation, may play a role in development of the tumor phenotype. The proposed hypothesis regarding acetylation of Rb2/p130 in tumor VS normal cells was found to be true in our case study of 36 tumor samples. Statistical analysis of results suggest strong correlation among Rb2/p130 acetylation and cancer phenotype.