Fraz Arshad Malik

COMSATS Institute of Information Technology, Islāmābād, Islamabad Capital Territory, Pakistan

Are you Fraz Arshad Malik?

Claim your profile

Publications (11)13.8 Total impact

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: 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􀀝􀀃􀀺􀁈􀀃􀁉􀁒􀁘􀁑􀁇􀀃􀁄􀁑􀀃􀁒􀁙􀁈􀁕􀁄􀁏􀁏􀀃􀁄􀀃􀁖􀁌􀁊􀁑􀁌􀃀􀁆􀁄􀁑􀁗􀀏􀀃􀁚􀁈􀁄􀁎􀀃􀁌􀁑􀁙􀁈􀁕􀁖􀁈􀀃􀁄􀁖􀁖􀁒􀁆􀁌􀁄􀁗􀁌􀁒􀁑􀀃􀁅􀁈􀁗􀁚􀁈􀁈􀁑􀀃􀁅􀁕􀁈􀁄􀁖􀁗􀀃 cancer risk and the 677TT genotype and an inverse association with the 1298C variant. These results for MTHFR 􀁓􀁒􀁏􀁜􀁐􀁒􀁕􀁓􀁋􀁌􀁖􀁐􀀃􀁐􀁌􀁊􀁋􀁗􀀃􀁅􀁈􀀃􀁓􀁒􀁓􀁘􀁏􀁄􀁗􀁌􀁒􀁑􀀃􀁖􀁓􀁈􀁆􀁌􀃀􀁆􀀃􀁌􀁑􀀃􀁖􀁓􀁒􀁕􀁄􀁇􀁌􀁆􀀃􀁅􀁕􀁈􀁄􀁖􀁗􀀃􀁆􀁄􀁑􀁆􀁈􀁕􀀃􀁄􀁉􀁉􀁈􀁆􀁗􀁈􀁇􀀃􀁓􀁄􀁗􀁌􀁈􀁑􀁗􀁖􀀃􀁅􀁘􀁗􀀃􀁐􀁄􀁑􀁜􀀃􀁒􀁗􀁋􀁈􀁕􀀃􀁉􀁄􀁆􀁗􀁒􀁕􀁖􀀃 􀁑􀁈􀁈􀁇􀀃􀁗􀁒􀀃􀁅􀁈􀀃􀁈􀁛􀁆􀁏􀁘􀁇􀁈􀁇􀀃􀁅􀁈􀁉􀁒􀁕􀁈􀀃􀁐􀁄􀁎􀁌􀁑􀁊􀀃􀃀􀁑􀁄􀁏􀀃􀁆􀁒􀁑􀁆􀁏􀁘􀁖􀁌􀁒􀁑􀁖􀀃􀁌􀁑􀁆􀁏􀁘􀁇􀁌􀁑􀁊􀀃􀁉􀁒􀁏􀁄􀁗􀁈􀀃􀁌􀁑􀁗􀁄􀁎􀁈􀀏􀀃􀁓􀁒􀁓􀁘􀁏􀁄􀁗􀁌􀁒􀁑􀀃􀁄􀁑􀁇􀀃􀁇􀁌􀁖􀁈􀁄􀁖􀁈􀀃􀁋􀁈􀁗􀁈􀁕􀁒􀁊􀁈􀁑􀁈􀁌􀁗􀁜􀀑
    􀀤􀁖􀁌􀁄􀁑􀀃􀀳􀁄􀁆􀁌􀃀􀁆􀀃􀀭􀀃􀀦􀁄􀁑􀁆􀁈􀁕􀀃􀀳􀁕􀁈􀁙. 07/2012; 13(4):1599-1603.
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: 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. 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. 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. 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.
    Asian Pacific journal of cancer prevention: APJCP 01/2012; 13(4):1599-603. · 1.50 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Several polymorphisms in the CYP1A1 locus have been identified and their genotypes appear to exhibit population frequencies that depend on ethnicity. In this study, we assessed the role of CYP1A1 genotype in 388 head and neck cancer patients in Pakistani population via a case-control study. Polymerase chain reaction (PCR) and single stranded conformational polymorphism assays were used. Most of the patients (51%) enrolled for the study, were from the age group of 40 to 60 years (±16.59). Mean age of the cancer patients involved in the study was 48 ± 16.59 years. Statistical analysis has shown that, tobacco users have more chances of head and neck cancer (P < 0.05) than non tobacco users, whereas male to female ratio is 1:1 (P > 0.05). Jobless persons are more prone to head and neck cancer (P < 0.01) compared with employers and housewives. After the genetic analysis, it was found that no already reported variants of CYP1A1 gene were found in Pakistani population. A novel mutation in CYP1A1 gene at exon 2 in 21 patients (P < 0.001, Odd Ratio (OR) = 9.4 and 95% confidence interval (CI) 1.3 to 70.8) has been found with a serine formation instead of tyrosine at amino acid 110. The patients showing this mutation have the mean age of 51.75 (±15.7). Therefore, mutation in CYP1A1 gene may be one of several factors that increase the chance of developing head and neck cancer.
    AFRICAN JOURNAL OF BIOTECHNOLOGY 07/2011; 10:5273-5280. · 0.57 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Metastasis suppressor genes are involved in the inhibition of a cancer cell's ability to metastasize. Down expression of such genes may contribute to pathogenesis of breast cancer. The aim of current study was firstly to evaluate expression of two examples, KAI1 and KISS1, and then to determine relationships with stages of breast cancer in a Pakistani population. Fresh biopsy tissues were collected from different hospitals and oncology research institutes. The semi quantitative reverse transcriptase polymerase chain reaction was used to investigate KAI1 and KISS1 expression in 25 breast tumor tissues and 25 normal tissues. Statistical analysis was performed to explore its association with breast cancer risk. The present study revealed that KAI1 and KISS1 mRNA expression was markedly reduced in tissues of breast cancer compared to adjacent normal tissue. In present study a splice variant of KAI1 during a screen for its expression analysis was also observed. This splice variant has not been reported previously. Metastasis suppressor genes demonstrate reduced expression in breast cancers in Pakistan.
    Asian Pacific journal of cancer prevention: APJCP 01/2011; 12(10):2785-91. · 1.50 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Xenobiotics are metabolized by either phase I enzymes like CYP1A1 or phase II enzymes like GSTs. Polymorphisms in the encoding genes (CYP1A1, GSTM1, GSTT1 and GSTP1) potentially may therefore contribute towards risk association for oral cancer. These genes were investigated via a case control study consisting of 228 oral cancer patients and 150 cancer free normal individuals as controls. DNA was extracted from WBCs for genotyping. Polymerase chain reaction-single stranded conformational polymorphism (SSCP) was used for screening CYP1A1 and GSTP1 genes mutations. Deletion of GSTM1 and GSTT1 genes were analyzed by multiplex PCR. Two novel mutations were found in this study in relation to oral cancer. A substitution mutation of A2842 with C resulting in missense tyrosine to serine formation along with a frameshift mutation due to insertion of thymidine at nucleotide 2842 resulting in 495 nucleotide sequence to alter was found in oral cancer patients. GSTM1 and GSTT1 deletion polymorphism was found in significantly higher number of individuals (OR=2.08, CI 1.05-4.2; OR=1.5, CI 0.9-2.4 respectively) compared to controls. 10 patients had deletion of both GSTM1 and GSTT1 genes. GSTP1 gene was also found to have novel substitution mutations of A2848 to T and G2849 to A in exon 7 resulting in leucine to leucine and alanine to threonine formation respectively. Two intronic deletions of cytosine at positions 1074 and 1466 was found in intron 3 and 4 in patients and no control had these exonic or intronic variants in GSTP1 gene. These results suggest that accumulation of genetic changes in CYP1A1, GSTM1, GSTT1 and GSTP1 genes are associated with increased risk of oral cancer.
    Asian Pacific journal of cancer prevention: APJCP 01/2011; 12(2):491-5. · 1.50 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Glutathione S-transferases constitute the phase II detoxification enzymes involved in the metabolism and detoxification of a wide range of potential environmental carcinogens. GSTM1 and GSTT1 are polymorphic and their deletions have been found to be associated with breast cancer risk in some of the world populations. The current study was aimed at evaluation of GSTM1 and GSTT1 gene deletions in 150 unrelated breast cancer patients and 150 healthy controls from Pakistani population. Multiplex PCR assay along with CYP1A1 exon 7 as an internal control was used. Our sampled patients and controls had a mean age of 48 (+11.8) and 45 (+7.9) years respectively. The analysis suggested that only 2% breast cancer patient and 8% controls had homozygous GSTM1 gene deletions (OR 0.23, 95% CI 0.06-0.85). A total of 8.7% patients and 18.6% controls had homozygous GSTT1 deletion (OR 0.41, 95% CI 0.25-0.83). The statistical analysis suggest that a non significant number (P>0.05) of individuals compared to controls have GSTM1 and GSTT1 gene deletions. Deletion in both genes was not observed in any of the patients or controls. The present case control study suggests no association of GSTM1 and GSTT1 gene deletions with sporadic form of breast cancer in Pakistani population.
    Asian Pacific journal of cancer prevention: APJCP 01/2011; 12(7):1749-52. · 1.50 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Xenobiotic metabolizing genes are involved in detoxification of carcinogens. Expression of these enzymes may be one of the reasons for interindividual differences in head and neck cancer risks. The aim of current study was first to evaluate the expression of CYP1A1, GSTM1, GSTT1 and GSTP1 and second to observe its relationship with stages of head and neck cancer in Pakistani population. Fresh biopsy tissues were taken from oncology institutional hospitals. Semi quantitative reverse transcriptase polymerase chain reaction was used to investigate CYP1A1, GSTM1, GSTT1 and GSTP1 expression in 49 head and neck cancer tumor tissue and 49 normal healthy tissues. Statistical analysis was performed to explore its association with head and neck cancer risk. The current study revealed that the CYP1A1 mRNA expression was markedly reduced in tissues of head and neck carcinoma compared to adjacent normal tissue (OR 4.5, CI 1.5-13.4). CYP1A1 expression was downregulated in 62.5% tissues of stage 1, 72.7% tissues of stage 2, 60% tissues of stage 3 and 100% tissues of stage 4. Undetectable or partial loss of expression of GSTM1 and GSTT1 mRNA was also observed at a higher rate in head and neck cancer tissue compared to control (OR 4.5, CI 1.5- 13.4 and OR 3.2, CI 1.1- 9.6 respectively). GSTM1 and GSTT1 expression was also downregulated in stage wise pattern; stage 1 had 50% and 12.5% tissues showing down regulation of GSTM1 and GSTT1 genes respectively, both GSTM1 and GSTT1 had 55% tissues with down regulation in stage 2, similarly stage 3 had 60% tissues showing down regulation of these genes and stage 4 had 86% and 71% tumors. GSTP1 mRNA expression was significantly higher in cancer tissue as in control tissue (OR 4.2, CI 1.2- 15.3). GSTP1 over expression also revealed related to stages with 36.4%, 60% and 71% tumor of stage 2, 3 and 4 respectively. Our results revealed that CYP1A1, GSTM1 and GSTT1 are downregulated in the head and neck cancer progression while GSTP1 is upregulated. These down regulations and up regulation were more marked in advanced stages of head and neck cancer. Therefore, CYP and GST expression may be an important mechanism involved in the carcinogenesis but the underlying mechanisms leading to such regulations in expression deserve further investigations.
    Asian Pacific journal of cancer prevention: APJCP 01/2011; 12(2):377-82. · 1.50 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Polymorphic deletions of GSTM1 and GSTT1 genes involved in the detoxification of potentially carcinogenic agents may be risk factors for various cancers, including head and neck cancer (HNC). In the present case-control study we aimed to access possible associations of HNC with GSTM1 and GSTT1 null genotypes in a Pakistani population. DNA was extracted from leukocytes of 388 cancer patients and 150 healthy controls by phenol-chloroform procedure. GSTM1 and GSTT1 deletion variants were genotyped by multiplex PCR assay with CYP1A1 as an internal control and further analyzed by primer specific PCR assay and sequencing. Mean age of cases and controls was 48 (±16.6) years with a male to female ratio of 1:1. Cancer of the oral cavity (57%) was most prevalent in the sampled population followed by pharynx and larynx (30% and 13% respectively). A statistically significant (P<0.05) association was observed for both null genotypes in contribution to HNC as compared with the controls. The odds ratio (OR) for the GSTM1 null genotype was 2.3 with a 95% CI of 1.5-5.5 and for GSTT1 OR was 2.04 with 95% CI of 1.3-3.1. These results suggest that the GSTM1 and GSTT1 null genotypes are risk factors for HNC development among the Pakistani population.
    Asian Pacific journal of cancer prevention: APJCP 01/2010; 11(4):881-5. · 1.50 Impact Factor
  • Fraz Arshad Malik, Andrew J Sanders, Wen G Jiang
    [Show abstract] [Hide abstract]
    ABSTRACT: CD82, also known as KAI-1, structurally belongs to tetraspanin family while categorised as metastasis suppressor gene on functional grounds. KAI1/CD82 is localized on cell membrane and form interactions with other tetraspanins, integrins and chemokines which are respectively responsible for cell migration, adhesion and signalling. In recent years apart from its significant involvement in the suppression of secondary tumours it has also been observed that KAI1/CD82 plays a vital role in virus binding and its entry inside the cell. Decreased expression of KAI1/CD82 molecule results in aggravating cancer progression. Altered expression levels of KAI1/CD82 molecule in different types of human cancer have been implicated as having prognostic value and linking to the long term survival of the patients. Increased level of KAI1/CD82 also results in the suppression of secondary tumour growth. Increased expression of this molecule results in reduced cell invasion and cell migration due to endocytosis of epidermal growth factor receptors (EGFR). Thus, KAI-1/CD82 is a pivotal molecule in the regulation of cancer cells' behaviour and has important clinical and therapeutic implications in cancer.
    Histology and histopathology 05/2009; 24(4):519-30. · 2.28 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: KAI1, also known as CD82, has been shown to have a potential impact on the invasiveness of cancer cells. In the present study, expression pattern of KAI1, both at transcription and translation levels and the potential clinical value of the expression were explored in a cohort of normal and ductal mammary cancer tissues (n=71). A marked reduction of KAI1 transcript was observed in invasive ductal breast tumours as compared to normal tissues. Expression of KAI1 protein was higher in normal tissues as compared to tumour samples. Though no significant difference of KAI1 expression between different grades of tumour was observed (p=0.064), significant correlation of TNM staging with KAI1 expression has been observed in invasive ductal breast cancer patients (p=0.045). Additionally, it was also observed that patients showing higher expression of KAI1 had a longer 10-year survival rate as compared to a low level or completely negative expression KAI1 (p=0.0136). KAI1 inverse correlation with tumour progression may be used as a strong prognostic marker.
    International Journal of Molecular Medicine 03/2009; 23(2):273-8. · 1.96 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Hereditary artifacts in BRCA1 gene have a significant contributory role in familial cases of breast cancer. However, its germline mutational penetrance in sporadic breast cancer cases with respect to Pakistani population has not yet been very well defined. This study was designed to assess the contributory role of germline mutations of this gene in sporadic cases of breast cancer. 150 cases of unilateral breast cancer patients, with no prior family history of breast cancer and no other disorders or diseases in general with age range 35-75 yrs, were included in this study.Mutational analysis for hot spots on Exon 2, 3 and 13 of BRCA1 was done by using Single Strand Conformational Polymorphism (SSCP). Sequence analysis revealed five variants (missense) and one novel splice site mutation at exon 13. No germline mutation was observed on the remaining exons with respect sporadic breast cancer cases in Pakistani population. A vast majority of breast cancer cases are sporadic; the present study may be helpful for designing a better genetic screening tool for germline BRCA mutations in sporadic breast cancer patients of Pakistani population. Further studies involving a screening of entire coding region of BRCA1 is required to explore the merits of genetic diagnosis and counseling in breast cancer patients.
    International Seminars in Surgical Oncology 09/2008; 5:21.