A Thesis Report on Nucleotide Polymorphism
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Added on 2022-02-17
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In the history of human civilization, science and technology have developed at an astounding rate. With that continuity, medical science has made significant progress in the last few centuries. As well as uncovering successfully treating old diseases, our researchers have also discovered effective treatment for newly-developed diseases.
A Thesis Report on Nucleotide Polymorphism
Added on 2022-02-17
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Association of Single Nucleotide Polymorphism with DNA Repair
Genes in Cervical Cancer among Bangladeshi Population
A THESIS REPORT
Submitted for the degree of
Master of Pharmacy (M. Pharm.)
Submitted By
Examination Roll No.: MS-181126
Examination Session: 2017-2018
Pharmacy Discipline
Life Science School, Khulna University
Khulna – 9208
DECEMBER, 2020
Genes in Cervical Cancer among Bangladeshi Population
A THESIS REPORT
Submitted for the degree of
Master of Pharmacy (M. Pharm.)
Submitted By
Examination Roll No.: MS-181126
Examination Session: 2017-2018
Pharmacy Discipline
Life Science School, Khulna University
Khulna – 9208
DECEMBER, 2020
Dedicated
To
My Beloved Parents
&
My Respected Supervisor
To
My Beloved Parents
&
My Respected Supervisor
DECLARATION
This is to certify that the thesis work entitled “Association of single nucleotide
polymorphism with DNA repair genes in cervical cancer among Bangladeshi
population” has been carried out by Laboni Das, examination roll no. MS-181126, session
2017-2018 in the Pharmacy Discipline, Khulna University, Khulna, Bangladesh. The above
thesis work or any part of this work has not been submitted in anywhere for the award of any
degree or diploma.
Signature of Candidate Signature of Supervisor
Laboni Das Professor Dr. Md. Mustafizur Rahman
This is to certify that the thesis work entitled “Association of single nucleotide
polymorphism with DNA repair genes in cervical cancer among Bangladeshi
population” has been carried out by Laboni Das, examination roll no. MS-181126, session
2017-2018 in the Pharmacy Discipline, Khulna University, Khulna, Bangladesh. The above
thesis work or any part of this work has not been submitted in anywhere for the award of any
degree or diploma.
Signature of Candidate Signature of Supervisor
Laboni Das Professor Dr. Md. Mustafizur Rahman
APPROVAL
This is to certify that the thesis work submitted by Laboni Das entitled ―Association of
single nucleotide polymorphism with DNA repair genes in cervical cancer among
Bangladeshi population” has been approved by the Examination Committee for the partial
fulfillment of the requirements for the degree of Master of Pharmacy (M. Pharm) in the
Pharmacy Discipline, Khulna University, Khulna, Bangladesh in December, 2020.
Board of Examiner (or Examination Committee)
1. ....................................... Chairman of the Committee
Name :
Designation :
University :
2. ....................................... Member
Name :
Designation :
University :
3. ....................................... Member
Name :
Designation :
University :
4. ....................................... Member
Name :
Designation :
University :
This is to certify that the thesis work submitted by Laboni Das entitled ―Association of
single nucleotide polymorphism with DNA repair genes in cervical cancer among
Bangladeshi population” has been approved by the Examination Committee for the partial
fulfillment of the requirements for the degree of Master of Pharmacy (M. Pharm) in the
Pharmacy Discipline, Khulna University, Khulna, Bangladesh in December, 2020.
Board of Examiner (or Examination Committee)
1. ....................................... Chairman of the Committee
Name :
Designation :
University :
2. ....................................... Member
Name :
Designation :
University :
3. ....................................... Member
Name :
Designation :
University :
4. ....................................... Member
Name :
Designation :
University :
ACKNOWLEDGEMENT
First of all, all praises be to the Almighty God, who enabled me to undertake & complete this
thesis work & finally write up the outcome. Individual efforts alone can never contribute in
totality to a successful completion of any venture. I would be failing in my duty if I did not
state my gratitude & appreciate to the following individuals who have made the valuable
contribution toward the thesis work.
I would like to express my deep gratitude & warm regards to my guide & thesis supervisor,
Dr. Md. Mustafizur Rahman, Professor, Pharmacy Discipline, Khulna University, for his
inspiration, constant guidance, valuable suggestions, sympathetic advice, and encouragement
during the course of study.
I would also like to convey my gratitude to my respected teacher and co-supervisor, Prof. Dr.
Samir Kumar Sadhu, Professor, Pharmacy Discipline, Khulna University, whose knowledge
and assistance helped this work to be successful.
I also wish to express my deepest gratitude to Dr. Ashis Kumar Das, Professor & Head,
Pharmacy Discipline, and all other respected teachers of Pharmacy Discipline for their noble
assistance, valuable guidance and inspiration.
My cordial thanks and gratitude to Robiul Islam, Asst. Register of lab, & Md. Ashikul Islam,
Lab. Assistant, Pharmacy Discipline, Khulna University for their kind and friendly
cooperation.
I also extend my gratitude to to all of my classmates and friends for their friendly co-
operations and occasional help. Last but not the least I am grateful to the authorities of the
Khulna University, for extending full laboratory facilities.
December, 2020 The Author
First of all, all praises be to the Almighty God, who enabled me to undertake & complete this
thesis work & finally write up the outcome. Individual efforts alone can never contribute in
totality to a successful completion of any venture. I would be failing in my duty if I did not
state my gratitude & appreciate to the following individuals who have made the valuable
contribution toward the thesis work.
I would like to express my deep gratitude & warm regards to my guide & thesis supervisor,
Dr. Md. Mustafizur Rahman, Professor, Pharmacy Discipline, Khulna University, for his
inspiration, constant guidance, valuable suggestions, sympathetic advice, and encouragement
during the course of study.
I would also like to convey my gratitude to my respected teacher and co-supervisor, Prof. Dr.
Samir Kumar Sadhu, Professor, Pharmacy Discipline, Khulna University, whose knowledge
and assistance helped this work to be successful.
I also wish to express my deepest gratitude to Dr. Ashis Kumar Das, Professor & Head,
Pharmacy Discipline, and all other respected teachers of Pharmacy Discipline for their noble
assistance, valuable guidance and inspiration.
My cordial thanks and gratitude to Robiul Islam, Asst. Register of lab, & Md. Ashikul Islam,
Lab. Assistant, Pharmacy Discipline, Khulna University for their kind and friendly
cooperation.
I also extend my gratitude to to all of my classmates and friends for their friendly co-
operations and occasional help. Last but not the least I am grateful to the authorities of the
Khulna University, for extending full laboratory facilities.
December, 2020 The Author
ABSTRACT
Background: Cervical cancer is the fourth most frequently diagnosed female malignancy as
well as the fourth leading cause of death in women worldwide. X-Ray Repair Cross
Complementing-3(XRCC3), a DNA repair gene plays an important role in maintaining
chromosomal stability and repairing DNA damage caused by exposures to radiation and
DNA cross-linking. This study was performed to investigate the relationship between XRCC3
Thr241Met polymorphism and cervical cancer risk in Bangladeshi females.
Method: The study included 124 cervical cancer patients and 150 healthy controls.
Genotyping of the study population was carried out by polymerase chain reaction-restriction
fragment length polymorphism (PCR–RFLP) analysis.
Results: Our study revealed that both heterozygous (C/T) and combined heterozygous plus
variant homozygous (C/T+T/T) genotypes were significantly associated with cervical cancer
susceptibility (OR =1.74, 95% CI = 1.02 to 2.94, p=0.0408 and OR =1.799, 95% CI = 1.07 to
3.01, p= 0.0259, respectively). Here C/T genotypes showed 1.74 times and combined
C/T+T/T genotypes showed 1.80 times higher risk of developing cervical cancer in our
population compared to normal homozygous C/C genotypes. However, mutant homozygous
T/T genotypes did not show statistically significant association with cervical cancer risk.
Comparing the allelic distribution we found that frequency of ̳C‘ and ̳T‘ alleles in cervical
cancer cases were found to be 79.43 and 20.56%, respectively, whereas in healthy controls
that were 86.66 and 13.33%, respectively. T allele increased the risk of cervical cancer
susceptibility by 1.68 times compared to C allele in Bangladeshi females (OR =1.68, 95% CI
= 1.06 to 2.64, p=0.0245).
Conclusion: Our study suggests that XRCC3 241-T allele carrier (C/T+T/T) represents an
increased risk of cervical cancer development in Bangladeshi women.
Background: Cervical cancer is the fourth most frequently diagnosed female malignancy as
well as the fourth leading cause of death in women worldwide. X-Ray Repair Cross
Complementing-3(XRCC3), a DNA repair gene plays an important role in maintaining
chromosomal stability and repairing DNA damage caused by exposures to radiation and
DNA cross-linking. This study was performed to investigate the relationship between XRCC3
Thr241Met polymorphism and cervical cancer risk in Bangladeshi females.
Method: The study included 124 cervical cancer patients and 150 healthy controls.
Genotyping of the study population was carried out by polymerase chain reaction-restriction
fragment length polymorphism (PCR–RFLP) analysis.
Results: Our study revealed that both heterozygous (C/T) and combined heterozygous plus
variant homozygous (C/T+T/T) genotypes were significantly associated with cervical cancer
susceptibility (OR =1.74, 95% CI = 1.02 to 2.94, p=0.0408 and OR =1.799, 95% CI = 1.07 to
3.01, p= 0.0259, respectively). Here C/T genotypes showed 1.74 times and combined
C/T+T/T genotypes showed 1.80 times higher risk of developing cervical cancer in our
population compared to normal homozygous C/C genotypes. However, mutant homozygous
T/T genotypes did not show statistically significant association with cervical cancer risk.
Comparing the allelic distribution we found that frequency of ̳C‘ and ̳T‘ alleles in cervical
cancer cases were found to be 79.43 and 20.56%, respectively, whereas in healthy controls
that were 86.66 and 13.33%, respectively. T allele increased the risk of cervical cancer
susceptibility by 1.68 times compared to C allele in Bangladeshi females (OR =1.68, 95% CI
= 1.06 to 2.64, p=0.0245).
Conclusion: Our study suggests that XRCC3 241-T allele carrier (C/T+T/T) represents an
increased risk of cervical cancer development in Bangladeshi women.
Chapter one
Introduction
Introduction
1. Introduction
The thousands of years history of human civilization is the history of abundant development
in science and technology. With that continuity medical science has seen dramatic
development in last couple of centuries. Besides discovering successful treatments of
commonly known old diseases our researchers have also been discovering the right ways of
dealing with newly originated challenging diseases. But despite of the vast success,
researchers are still working tirelessly to discover the successful remedy for some old but
strong diseases. One of these stubborn lethal diseases is cancer.
1.1 Cancer
Cancer is a disease that sffeffa the body's cells. Cancer is known as a group of disease
complications which are commonly characterized by the uncontrolled growth and
proliferation of cells, resulting in death. One defining feature of cancer is the rapid creation of
abnormal cells which grow beyond their usual boundaries, and which can invade adjoining
parts of the body and spread to other organs. Cancer can start any place in the body. It starts
when cells grow out of control and crowd out normal cells. This makes it hard for the body to
work the way it should. It is indeed a pandemic burden affecting people of all ages, races,
incomes, and statuses; principally by commencing a state of sustaining proliferative
signaling, avoiding the growth suppressors, protecting the defective cell death, accelerating
the replicative immortality, inducing angiogenesis, and finally by activating invasion and
metastasis [Torre et al 2012].
Cancer is also characterized by acquisition of metastatic properties. In most cases, activation
of oncogenes and deactivation of tumor suppressor genes lead to uncontrolled cell cycle
progression and inactivation of apoptotic mechanisms [Vogelstein et al 2004]. rsnfeC
The thousands of years history of human civilization is the history of abundant development
in science and technology. With that continuity medical science has seen dramatic
development in last couple of centuries. Besides discovering successful treatments of
commonly known old diseases our researchers have also been discovering the right ways of
dealing with newly originated challenging diseases. But despite of the vast success,
researchers are still working tirelessly to discover the successful remedy for some old but
strong diseases. One of these stubborn lethal diseases is cancer.
1.1 Cancer
Cancer is a disease that sffeffa the body's cells. Cancer is known as a group of disease
complications which are commonly characterized by the uncontrolled growth and
proliferation of cells, resulting in death. One defining feature of cancer is the rapid creation of
abnormal cells which grow beyond their usual boundaries, and which can invade adjoining
parts of the body and spread to other organs. Cancer can start any place in the body. It starts
when cells grow out of control and crowd out normal cells. This makes it hard for the body to
work the way it should. It is indeed a pandemic burden affecting people of all ages, races,
incomes, and statuses; principally by commencing a state of sustaining proliferative
signaling, avoiding the growth suppressors, protecting the defective cell death, accelerating
the replicative immortality, inducing angiogenesis, and finally by activating invasion and
metastasis [Torre et al 2012].
Cancer is also characterized by acquisition of metastatic properties. In most cases, activation
of oncogenes and deactivation of tumor suppressor genes lead to uncontrolled cell cycle
progression and inactivation of apoptotic mechanisms [Vogelstein et al 2004]. rsnfeC
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