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Marine n-3 fatty acid intake, glutathione s-transfrases (GST) polymorphisms and colorectal cancer risk: the Singapore Chinese Health Study

Cui, Chendi (2016) Marine n-3 fatty acid intake, glutathione s-transfrases (GST) polymorphisms and colorectal cancer risk: the Singapore Chinese Health Study. Master's Thesis, University of Pittsburgh. (Unpublished)

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Abstract

The role of marine n-3 polyunsaturated fatty acids (PUFAs) in colorectal carcinogenesis has been investigated in many epidemiological studies; however, the epidemiological evidence is inconclusive. A potential explanation is due to competing products of n-3 PUFAs metabolism. Anti-inflammatory eicosanoids, products of n-3 PUFAs metabolism through cyclooxygenase (COX) enzymes, could inhibit inflammatory responses, which have a protective effect against colorectal cancer. Alternatively, malondialdehyde (MDA) and 4-hydroxy-2-hexenal (4-HHE), lipid peroxidation products of marine n-3 PUFAs, could be mutagenic. It has been suggested that glutathione S-transferases (GSTs) are involved in removing lipid peroxidation products. Therefore, we investigated whether GST genotypes (i.e., GSTT1, GSTM1) modified the marine n-3 PUFAs-colorectal cancer association using a nested case-control study within the Singapore Chinese Health Study. With 469 incident colorectal cancer cases and 1,167 noncases, we observed the effect modification of combined GSTT1 and GSTM1 positive genotypes with marine n-3 PUFAs on colorectal cancer (p for interaction < 0.01), and with the ratio of marine n-3 to n-6 PUFAs on colorectal cancer (p for interaction = 0.01). An inverse association of marine n-3 PUFAs with colorectal cancer was observed among those with high activity GST genotypes (i.e., combined GSTM1 and GSTT1 positive genotype) [Odds ratio (OR) for Q4 vs. Q1 = 0.57, 95% CI = 0.32-1.01, p for trend <0.05]; however, a positive association was observed among those with one or more GST null genotypes [OR for Q4 vs. Q1 = 1.49, 95% CI = 1.00-2.23, p for trend = 0.01]. Among those with one or more GST null genotypes, a positive association was also shown for the ratio of marine n-3 to n-6 PUFAs and colorectal cancer [OR for Q4 vs. Q1 = 1.64, 95% CI = 1.09-2.37, p for trend < 0.01], although no statistically significant association was observed for high activity GST genotypes. Our results suggest the role of GSTT1 and GSTM1 in the association between marine n-3 PUFAs and colorectal cancer. This finding provided a point to consider GST genotypes in the marine n-3 PUFAs-colorectal cancer association in the population. It is important for further public health intervention program to consider this interaction while intervening on the population.


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Details

Item Type: University of Pittsburgh ETD
Status: Unpublished
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Cui, Chendichc217@pitt.eduCHC2170000-0002-7022-4486
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Thesis AdvisorButler, Lesley M.butlerl3@pitt.eduBUTLERL3
Committee MemberBertolet, Marniemhb12@pitt.eduMHB12
Committee MemberKammerer, Candace Mcmk3@pitt.eduCMK3
Date: 9 September 2016
Date Type: Publication
Defense Date: 3 June 2016
Approval Date: 9 September 2016
Submission Date: 1 June 2016
Access Restriction: 1 year -- Restrict access to University of Pittsburgh for a period of 1 year.
Number of Pages: 82
Institution: University of Pittsburgh
Schools and Programs: Graduate School of Public Health > Epidemiology
Degree: MS - Master of Science
Thesis Type: Master's Thesis
Refereed: Yes
Uncontrolled Keywords: colorectal cancer, diet, marine n-3 polyunsaturated fatty acids, glutathione S-transferase
Date Deposited: 09 Sep 2016 19:05
Last Modified: 01 Jul 2017 05:15
URI: http://d-scholarship.pitt.edu/id/eprint/28111

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