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Association of DNA Repair Gene Variants with Pancreatic Cancer in Patients with Chronic Pancreatitis

Das, Siddhartha (2013) Association of DNA Repair Gene Variants with Pancreatic Cancer in Patients with Chronic Pancreatitis. Master's Thesis, University of Pittsburgh. (Unpublished)

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Abstract

Background: Pancreatic cancer (PC) is one of the most devastating cancers with less than 5% surviving after five years of diagnosis. Most of the risk factors have non-specific odds ratio except for chronic pancreatitis (CP) which has an extremely high odds ratio as reported in the literature. CP is characterized by inappropriate activation of trypsinogen in the pancreas resulting in inflammation of the pancreas. Most of the genetic factors behind the inflammatory to cancerous progression still remain unexplained. This research study describes identification of multiple non-synonymous mutations and implicates specific DNA repair pathways in the risk of progression from CP to PC.
Methods: Whole exome sequencing was carried out in 16 CP individuals with PC and 11 individuals without PC, following which the thousand genomes project data was used to identify the rare and novel germline non-synonymous variants among 159 DNA repair genes and burden test of DNA repair pathways was used to identify the most frequently mutated DNA repair pathways.
Results: We were able to able to identify at least 30 rare and novel non-synonymous germline variants at sufficient read depth in our CP+PC cohort that warrant investigation in pancreatic cancer tumor tissues as well as larger PC patient cohorts.
Public Health Significance: The public health significance of this work lies in the fact that it provides for the first time an opportunity to genetically screen the potentially high risk pancreatic cancer patient cohorts to determine their individual risk of development of the disease and based on risk assessment, a strategy could be developed to determine if an individual needs to undergo high risk surgical procedures like total pancreatectomy to reduce their risk of developing pancreatic cancer or develop changes in their habits to reduce the possibility of the development of pancreatic cancer.


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Details

Item Type: University of Pittsburgh ETD
Status: Unpublished
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Das, Siddharthasid10@pitt.eduSID10
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairWhitcomb, David C.whitcomb@pitt.eduWHITCOMB
Committee MemberFeingold, Eleanorfeingold@pitt.eduFEINGOLD
Committee MemberFerrell, Robert Erferrell@pitt.eduRFERRELL
Committee MemberShaffer, John Rjrs51@pitt.edu, john.r.shaffer@gmail.comJRS51
Date: 30 September 2013
Date Type: Publication
Defense Date: 11 July 2013
Approval Date: 30 September 2013
Submission Date: 23 July 2013
Access Restriction: 3 year -- Restrict access to University of Pittsburgh for a period of 3 years.
Number of Pages: 92
Institution: University of Pittsburgh
Schools and Programs: Graduate School of Public Health > Human Genetics
Degree: MS - Master of Science
Thesis Type: Master's Thesis
Refereed: Yes
Uncontrolled Keywords: Pancreatic Cancer, DNA repair
Date Deposited: 30 Sep 2013 14:11
Last Modified: 15 Nov 2016 14:14
URI: http://d-scholarship.pitt.edu/id/eprint/19441

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