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Shahnaz  Tofangchiha (1) Shahnaz  Tofangchiha (1)

Shahnaz Tofangchiha (1) - PowerPoint Presentation

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Shahnaz Tofangchiha (1) - PPT Presentation

Moeen Bonak Dar 1 Mohammad Hasan Tajadini 2 Mahyar Nourian 2 1 AJA Cancer Epidemiology Research and Treatment Center AJA CERTC AJA University of Medical Sciences Tehran Iran ID: 803650

cancer aja sciences mutations aja cancer mutations sciences mutation university center research iran medical tehran epidemiology treatment p53 chemical

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Slide1

Shahnaz Tofangchiha(1), Moeen Bonak Dar(1), Mohammad Hasan Tajadini(2), Mahyar Nourian(2*)1- AJA Cancer Epidemiology Research and Treatment Center (AJA- CERTC), AJA University of Medical Sciences, Tehran, Iran. 2- Biotechnology Department, Applied Physiology Research Center, Isfahan University of Medical Sciences, Isfahan, Iran.

1

AJA Cancer Epidemiology Research and Treatment Center (AJA- CERTC), AJA University of Medical Sciences, Tehran, Iran.

Mutations of Exons 5 and 6 in Tumor Suppressor Tp53 Gene in victims of chemical weapons

Dr. Shahnaz

Tofangchiha

Electronic Poster Code:

A-10-250-1

12-15/OCT/18

Slide2

Introduction2

AJA Cancer Epidemiology Research and Treatment Center (AJA- CERTC), AJA University of Medical Sciences, Tehran, Iran.Chemical weapons is one of non-conventional weapons that Iraq used them too much despite of it's legal prohibitions. Mustard gas is a potent alkylating agent above all other gases which affects DNA. It is expected that it can increase the risk of cancer in people who are exposed to it. P53 Protein is a well-known tumor suppressor which play an important role in the start of apoptosis. The mutant forms of this protein often lose function and may lead to P53 mutation be the most common genetic change in human cancers. According to the effect of P53 gene defect in the development of cancer and also mutation by chemical weapons, in this study we decided to evaluate exon 5 and 6 mutations using Scanning and HRM and Sequencing.

12-15/OCT/18

Slide3

Method3AJA Cancer Epidemiology Research and Treatment Center (AJA- CERTC), AJA University of Medical Sciences, Tehran, Iran.

12-15/OCT/18This study was a Cross sectional study with the goal of exploring exon 5 and 6 mutations of P53 gene by HRM Scanning method on victims of chemical attacks during the first six months of 1394 in Sasan Hospital. Data was collected by a questionnaire and then a blood sample was taken for DNA extraction. After DNA extraction by high resolution melting analysis and using the technique of overlapping ampelicon, the gene was explored on the pattern of melting. Finally, the results of study were analyzed by SPSS 19 statistical software.

Slide4

ResultIn this study there was 33 patients in the chemical group and 37 healthy in control group. All participants in the group were male. In the patient group, 3 cases was found with mutation (2 mutations in exon 5 and a mutation in exon 6) but there was no mutation in control group. There was no significant difference between the patient's condition and mustard gas exposure.

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AJA Cancer Epidemiology Research and Treatment Center (AJA- CERTC), AJA University of Medical Sciences, Tehran, Iran.

12-15/OCT/18

situation

numberage rangemean age ±SDP value

Healthy3746-6253.78±8.40.57Chemical3351-66

52.85±4.6Total

70

46-6653.34±6.86

Age survey

situation

mutation

no mutation

Chi-square

Lung cancer

1

0

X2=22.65

df

=1

P=0.04

Lack of lung cancer

1

68

total

2

68

Correlation between mutations in exon5 and lung cancer

Sample ID

Mutation

Protein change

Codon

Exon

S-9

524G>A

R175H

175

5

S-27

524G>AR175H1755S-18580C>TL194F1946

Mutations found in patients

Slide5

Discussion5AJA Cancer Epidemiology Research and Treatment Center (AJA- CERTC), AJA University of Medical Sciences, Tehran, Iran.

12-15/OCT/18According to the results of the study, all the victims were infected by mustard gas. Among all participants, only three patients were found with mutations: two mutations in exon 5 and one in exon 6 and all three patients had a history of lung cancer. But none of the mutations were observed in healthy individuals. The patient's condition (mutant or non-mutant) and lung cancer had a significant relationship, but It cannot be said that the relation sheep is definite due to small sample size.

Slide6

Conclusion6AJA Cancer Epidemiology Research and Treatment Center (AJA- CERTC), AJA University of Medical Sciences, Tehran, Iran.

12-15/OCT/18In our study there was no significant association between smoking and gene mutation. According to the effect of P53 gene defect in the development of cancer and also mutations caused by chemical weapons wider surveys about certain mutations in genes of chemical victims is suggested. So the small sample size it cannot be concluded that the relationship is definite.

Slide7

ReferencesKehe K, Steinritz D,

Balszuweit F, Thiermann H. Long-Term Effects of the Chemical Warfare Agent Sulfur Mustard. Chemical Warfare Toxicology2016. p. 179-90.Razavi SM, Saghafinia M, Salamati P. Paraclinical findings in Iranian veterans exposed to sulfur mustard gas: a literature review. Chinese journal of traumatology. 2017.Yue X, Zhao Y, Xu Y, Zheng M, Feng Z, Hu W. Mutant p53 in cancer: Accumulation, gain-of-function and therapy. Journal of Molecular Biology. 2017.Moll UM, Riou G, Levine AJ. Two distinct mechanisms alter p53 in breast cancer: mutation and nuclear exclusion. Proceedings of the National Academy of Sciences. 1992;89(15):7262-6.

Rashid Mir MM, Javid J,

Ahamad I, Farooq S, Yadav P, Zuberi M, et al. Clinical implications of cytosine deletion of exon 5 of P53 gene in non small cell lung cancer patients. South Asian journal of cancer. 2016;5(1):33.

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AJA Cancer Epidemiology Research and Treatment Center (AJA- CERTC), AJA University of Medical Sciences, Tehran, Iran.

12-15/OCT/18

Slide8

Final QuestionsWhat is already known about the subject?

What could be added to the current knowledge by this study?

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AJA Cancer Epidemiology Research and Treatment Center (AJA- CERTC), AJA University of Medical Sciences, Tehran, Iran.

12-15/OCT/18

Mustard reacts with nucleic acids and alkylates them, so may cause errors and disruptions in the replication of DNA or protein synthesis. According to previous studies, 20% to 25% of breast cancer and more than 50% of cancers of bladder, colon and lung had mutation in the P53 gene. These mutations are in different regions that are highly conserved in exons 5 to 10.

Mutations were seen in mustard gas victims and there was a significant correlation between the patient's condition (mutant or non-mutant) and lung cancer.

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