Page 1 |
Save page Remove page | Previous | 1 of 74 | Next |
|
small (250x250 max)
medium (500x500 max)
large ( > 500x500)
Full Resolution
All (PDF)
|
This page
All
Subset |
GENETIC VARIATION IN THE BASE EXCISION REPAIR PATHWAY,
ENVIRONMENTAL RISK FACTORS AND COLORECTAL ADENOMA RISK
by
Roman Corral
A Thesis Presented to the
FACULTY OF THE GRADUATE SCHOOL
UNIVERSITY OF SOUTHERN CALIFORNIA
In Partial Fulfillment of the
Requirements for the Degree
MASTER OF SCIENCE
(MOLECULAR EPIDEMIOLOGY)
August 2012
Copyright: 2012 Roman Corral
Object Description
| Title | Genetic variation in the base excision repair pathway, environmental risk factors and colorectal adenoma risk |
| Author | Corral, Roman |
| Author email | rcorral@med.usc.edu;rcorral@med.usc.edu |
| Degree | Master of Science |
| Document type | Thesis |
| Degree program | Molecular Epidemiology |
| School | Keck School of Medicine |
| Date defended/completed | 2012-08-08 |
| Date submitted | 2012-08-28 |
| Date approved | 2012-08-28 |
| Restricted until | 2012-08-28 |
| Date published | 2012-08-28 |
| Advisor (committee chair) |
Stern, Mariana C. Lewinger, Juan Pablo |
| Advisor (committee member) | Ingles, Sue |
| Abstract | Three inter-related and consistent factors emerging from the epidemiological literature for colorectal adenoma are cigarette smoking, alcohol intake, and dietary folate levels. Oxidative damage caused by these three factors can be repaired through the base excision repair pathway (BER). The ability to repair such damage may be modified by common genetic variants in BER pathway genes. In a sigmoidoscopy based study, we examined associations between 182 halplotype tagging single nucleotide polymorphisms (SNPs), which captured common genetic variation in 14 BER genes, and colorectal adenoma risk. Additionally, the interaction effects between SNPs and cigarette smoking, alcohol intake, and dietary folate levels were examined. Using logistic regression, per allele odds ratios (ORs) and 95% confidence intervals (CIs) were estimated for the association between SNPs and colorectal adenoma risk. Using multinomial logistic regression, per allele ORs and 95% CIs for each SNP were calculated after stratifying on adenoma location (rectal versus left colon) and adenoma size (< 1 cm versus ≥ 1 cm). Significant associations were observed between SNPs in BER genes (FEN1, NTHL1, APEX1) and colorectal adenoma risk. Significant associations were also observed between SNPs in the NEIL2 gene and rectal adenoma risk. SNPs in BER genes modified the effect of smoking (MUTYH), alcohol consumption (LIG3) and dietary folate (LIG3, XRCC1) on colorectal adenoma risk. The findings support our hypothesis that genetic variation in DNA repair genes can modify the association of key colorectal adenoma risk factors. Our findings support a role for oxidative damage induced by these exposures on colorectal cancer formation. |
| Keyword | colorectal adenoma; base excision repair; folate; alcohol; smoking |
| Language | English |
| Part of collection | University of Southern California dissertations and theses |
| Publisher (of the original version) | University of Southern California |
| Place of publication (of the original version) | Los Angeles, California |
| Publisher (of the digital version) | University of Southern California. Libraries |
| Provenance | Electronically uploaded by the author |
| Type | texts |
| Legacy record ID | usctheses-m |
| Rights | Corral, Roman |
| Access conditions | The author retains rights to his/her dissertation, thesis or other graduate work according to U.S. copyright law. Electronic access is being provided by the USC Libraries in agreement with the author, as the original true and official version of the work, but does not grant the reader permission to use the work if the desired use is covered by copyright. It is the author, as rights holder, who must provide use permission if such use is covered by copyright. The original signature page accompanying the original submission of the work to the USC Libraries is retained by the USC Libraries and a copy of it may be obtained by authorized requesters contacting the repository e-mail address given. |
| Repository name | University of Southern California Digital Library |
| Repository address | USC Digital Library, University of Southern California, University Park Campus MC 7002, 106 University Village, Los Angeles, California 90089-7002, USA |
| Repository email | cisadmin@usc.edu |
| Archival file | uscthesesreloadpub_Volume4/etd-CorralRoma-1171.pdf |
Description
| Title | Page 1 |
| Full text | GENETIC VARIATION IN THE BASE EXCISION REPAIR PATHWAY, ENVIRONMENTAL RISK FACTORS AND COLORECTAL ADENOMA RISK by Roman Corral A Thesis Presented to the FACULTY OF THE GRADUATE SCHOOL UNIVERSITY OF SOUTHERN CALIFORNIA In Partial Fulfillment of the Requirements for the Degree MASTER OF SCIENCE (MOLECULAR EPIDEMIOLOGY) August 2012 Copyright: 2012 Roman Corral |
Comments
Post a Comment for Page 1
