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Home > Spectrum of Tp53 Tumor Suppressor Gene Mutations and Codon 72 Polymorphism in Pakistani Female Breast Cancer Patients

Spectrum of Tp53 Tumor Suppressor Gene Mutations and Codon 72 Polymorphism in Pakistani Female Breast Cancer Patients

Thesis Info

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Author

Aziz, Ishrat

Program

PhD

Institute

University of the Punjab

City

Lahore

Province

Punjab

Country

Pakistan

Thesis Completing Year

2011

Thesis Completion Status

Completed

Subject

Natural Sciences

Language

English

Link

http://prr.hec.gov.pk/jspui/handle/123456789/1218

Added

2021-02-17 19:49:13

Modified

2024-03-24 20:25:49

ARI ID

1676727225537

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The tumor suppressor gene TP53 encodes a nuclear protein that prevents the cells from dividing before DNA damage is repaired. Mutations in TP53 gene have effects on its biological activities. The objectives of present study aims at determining the frequency TP53 mutations in sporadic, genetic lineage and analysis of the data i.e. questionnaire collected from breast cancer patients from Pakistan, during the study. Female breast cancer patients were recruited at Shaukat Khanum Memorial Cancer Hospital & Research Centre and Mayo Hospital, Lahore Pakistan, from January 2005-December 2008. A total of 150 sporadic breast cancer patients and three families with breast cancer cases were included in the study. From all study participants, a blood sample and a piece of tissue of normal and tumor both were collected. DNA was extracted and exons 5-8 (central region) of TP53 gene were PCR amplified. Each sample was heteroduplexed with a normal control sample (confirmed by sequencing). To screen TP53 mutations Temporal Temperature Gradient Gel Electrophoresis (TTGE) was performed. The mutations were confirmed by sequencing. Restriction Fragment Length Polymorphism (RFLP) was used for understanding the status of codon 72, exon 4 of TP53 gene polymorphism (arg/arg) in Pakistan. The data was analyzed using the R15 programme, provided by International Agency for Research on Cancer. Three deleterious mutations were detected in the sporadic breast cancer patients, viz., codon 238 where TGT is mutated to TAT (cys to tyr), codon 248 where CGG is mutated to CAG ( arg to glu), and codon 278 where CCT is mutated to TCT (pro to ser). These mutations were not detected in normal breast tissue and blood samples of these patients. R15 analysis (IARC, 2011) of TP53 gene mutations showed that the mutations detected in Pakistani breast cancer patients are reported most prevalent somatic mutations (codon 238 = 79 tumors, codon 248 = 779 tumors and codon 278 = 74 tumors) in breast cancer patients of the world. Three-dimensional structures were predicted by 3D Viewer (software given on IARC website) and found that all these three mutations are in DNA binding region of TP53 and could change the structure of protein and, therefore, affect its function. TP53 mutation has not been observed in normal persons and breast cancer families blood samples. One family was detected with Li-Fraumeni syndrome characters but TP53 mutations are not found in it. Although the polymorphism arg/arg, codon 72, exon 4 of TP53 gene is reported as a functional relevant polymorphism that contributes to breast cancer development yet in the vpresent study, genotype arg/pro and pro/pro, both polymorphisms were found more significant in Pakistani breast cancer patients as compared to arg/arg with corresponding ratio of arg/pro (53.3): pro/pro (34.6): arg/arg (12). Normal controls showed about the same difference in ratio of arg/pro: pro/pro: arg/arg, (50:40:10). Correlation of TP53 mutations with clinicopathological parameters (data collected by questionnaire) was observed. Patients were divided into two groups; group 1 (TP53 non mutated) and group 2 (TP53 mutated). As both groups have not shown any difference so no prominent correlation between TP53 mutations and clinicopathological parameters was found. It is concluded that the frequency of TP53 gene mutations in DNA coding region (5-8 exon ) is low in Pakistani breast cancer patients. However, present study is in favor of the fact that the frequency of TP53 gene mutations is different in different geographical areas. Genotype arg/arg is less prevalent in the female breast cancer patients and normal population of Pakistan. There was no significant correlation between TP53 mutation and tumor aggressiveness e.g. nodal status, size, ER/PR, histopathology etc. Epidemiologically, no carcinogen was found important as a causative factor of TP53 gene mutations in Pakistani breast cancer patients.
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ترجمہ کی اہمیت

ترجمہ کی اہمیت
ترجمہ :
ایک زبان میں لکھی ہوئی تحریر کو دوسری زبان میں منتقل کرنا ترجمہ کہلاتا ہے۔
ترجمہ کی اہمیت:
ترجمے کی روایت ہی ہمیں دوسری قوموں اور ممالک کے احوال و حالات سے آگاہی ہوتی ہے۔مثلا پہلی اور دوسری جنگ عظیم کے دوران ہونے والے واقعات ترجمہ نگاری کے بعد ہی ہم تک پہنچے ہیں۔ موجودہ زمانے میں پریس ریلیز کے ذریعے بیان جاری کیے جاتے ہیں اور ہمارے صحافی ان کو ہماری زبان میں ترجمہ کرتے ہیں۔
ترجمے ہی کے ذریعے سے دوسرے ممالک کے حالات حاضرہ کے بارے میں ہم جان پاتے ہیں۔ موسم، کھیلوں، تفریح اور کاروبار کے بارے میں جان پاتے ہیں۔عالمی سطح کی علمی و ادبی سرگرمیاں جو بین الاقوامی سطح پر وقوع پذیر ہوتی ہیں وہ بھی ترجمہ نگاری کی وجہ سے ہم تک پہنچتی ہیں۔ادب کی مختلف اصناف اور دنیا میں ہونے والی مختلف ادبی سرگرمیوں کے بارے میں آگاہی بھی ترجمہ نگاری کے ذریعے ہی ممکن ہو پاتی ہے۔
تنقید کی وجہ سے ادب میں آنے والی تبدیلیوں کی وجہ یہ ہے کہ ہم نے غیر ملکی ادب کو ترجمہ کرنے کے بعد پڑھا۔ترجمہ نگاری کے لیے تنقید کی اہمیت بہت زیادہ ہے۔ اسی طرح تحقیق کے لیے استعمال ہونے والے آلات کی وجہ سے ترجمہ نگاری کی اہمیت روز افزوں بڑھتی چلی جاتی ہے۔
کسی بھی علاقے اور معاشرے کے مزاج کے حوالے سے آگاہی بھی ترجمہ کیذریعے ہوتی ہے۔ ترجمہ کے ذریعے سے ہی کسی علاقے کی تاریخ کے بارے میں جانکاری حاصل ہوتی ہے۔ معاشرے کے رسم و رواج ، معمولات کا پتہ بھی ترجمہ نگاری سے چلتا ہے۔
ترجمہ نگاری کے ذریعے سائنسی ایجادات اور نت نئے تجربات سے واقفیت ہوتی ہے۔ مسلمان سائنسدانوں کی تحقیقات کا نچوڑ یعنی ان کی کتب کا ترجمہ کرکے اہل یورپ نے ان سے بھرپور...

The Knowledge, Attitude, and Practice about Fertility Preservation among Oncologist-A Cross-Sectional Study

BackgroundFertility Preservation is the process of saving or protecting a person’s ability to have children in the future. It is often considered for individuals to undergo medical treatments that may impact their fertility, such as chemotherapy. Hence, the current study is aimed to assess clinical practitioners’ knowledge, practice, and attitude toward fertility preservation among oncologists. MethodsA cross-sectional survey was carried out to identify the current knowledge, attitudes, and practices regarding fertility preservation among oncologists—a total of seventy-nine oncologists in Karachi working in different public and private sectors. The study was conducted between January to August 2022. The data was gathered using a self-designed questionnaire that was distributed via email. ResultsOne hundred and eighty oncologists were provided with the survey form via email. The response rate was 47.22% (n=85). Out of which, six questionnaires were excluded due to incomplete information. The total questionnaire analyzed was n=79, which included 58 (73.41%) males and 21 (16.59%) females. ConclusionThe results revealed that oncologists had a compromised knowledge regarding fertility preservation for cancer patients. Despite weak knowledge, most oncologists believe that more elaborative measures should be taken to overcome this issue.   DOI: https: //doi. Org/10.59564/amrj/01.01/004

Impact of Microfinance on Poverty

The primary objective of this thesis is to analyze the impact of microfinancing on poverty through a sample survey of four microfinance institutions, using concepts: like household income/expenditure, asset holdings and diversity, education and various measures of vulnerability at household and enterprise level. The study employed the tool developed in collaboration by Assessing the Impact of Microenterprise Services (AIMS) and Small Enterprise Education and Promotion network (SEEP). The tool has been modified in the local context. Face to face structured interviewing was used to collect primary data. Chi square test is used to analyze the difference between incoming (Less than one year) and established clients (2-5 years) on the basis of poverty indicators established at household and enterprise level. Role of demographic and other independent variable is analyzed with the help of multinomial regression analysis. The evidence turns out to be mixed one like (i) strong positive impact on children education and enterprise financial performance. (ii) mixed evidence on food security, household expenditures and household assets and no impact has been observed on housing and income smoothening of enterprise. Present study can be very useful to IA practitioners and policy makers. This research has made a significant contribution in unraveling some of the myths of microfinance hence advancing literature and research on this important issue. Keywords: Microfinance, Poverty Alleviation, Household Welfare, Enterprise Management, Impact Assessment.