Genetic Polymorphisms of CYP2E1, GSTP1, NQO1 and MPO and the Risk of Nasopharyngeal Carcinoma in a Han Chinese Population of Southern China
BMC Research Notes
Genetic Polymorphisms of CYP2E1, GSTP1, NQO1 and MPO and the Risk of Nasopharyngeal Carcinoma in a Han Chinese Population of Southern China
Xiuchan Guo 0 3
Yi Zeng 0
Hong Deng 2
Jian Liao 4
Yuming Zheng 2
Ji Li 1
Bailey Kessing 3
Stephen J O'Brien 1
0 State Key Laboratory for Infectious Diseases Prevention and Control, Institute for Viral Disease Control and Prevention, Chinese Centers for Disease Control and Prevention , Beijing , China
1 Laboratory of Genomic Diversity, National Cancer Institute , Frederick, MD 21702 , USA
2 Wuzhou Red Cross Hospital , Wuzhou 543002, Guangxi , China
3 Laboratory of Genomic Diversity, SAIC-Frederick, Inc., National Cancer Institute , Frederick, MD 21702 , USA
4 Cangwu Institute for Nasopharyngeal Carcinoma Control and Prevention , Wuzhou, Guangxi , China
Background: Southern China is a major area for endemic nasopharyngeal carcinoma (NPC). Genetic factors as well as environmental factors play a role in development of NPC. To investigate the roles of previously described carcinogen metabolism gene variants for NPC susceptibility in a Han Chinese population, we conducted a casecontrol study in two independent study population groups afflicted with NPC in Guangdong and Guangxi Provinces of southern China. Methods: Five single nucleotide polymorphisms (SNPs) of CYP2E1-rs2031920, CYP2E1-rs6413432, GSTP1-rs947894, MPO-rs2333227 and NQO1-rs1800566 were genotyped by PCR-based RFLP, sequencing and TaqMan assay in 358 NPC cases and 629 controls (phase I cohort). Logistic regression analysis was used to estimate odds ratios (OR) and 95% confidence intervals (CI). To confirm our results, sixteen tag SNPs for GSTP1, MPO, NQO1 (which 100% covered these genes), and 4 functional SNPs of CYP2E1 were genotyped in another cohort of 213 NPC cases and 230 controls (phase II cohort). Results: No significant associations in NPC risk were observed for the five polymorphisms tested in the phase I cohort. In an additional stratified analysis for phase I, there was no significant association between cases and controls in NPC high risk population (EBV/IgA/VCA positive population). Analysis of 14 tagging SNPs within the same genes in an independent phase II cohort were in agreement with no SNPs significantly associated with NPC. Conclusions: Our results suggest that polymorphism of CYP2E1, GSTP1, MPO and NQO1 genes does not contribute to overall NPC risk in a Han Chinese in southern China.
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Background
Nasopharyngeal carcinoma (NPC) is rare in most
regions of the world; however it is a common cancer in
southern China, especially in Guangdong and Guangxi
Provinces. The incidence rate of NPC for males is more
than 20 per 100,000 and up to 25-40 per 100,000 in
some areas bordering the Xijiang River and Pearl River
drainages in these two provinces[1,2]. Both
environmental and genetic factors have been associated with the
risk of developing NPC. Epidemiologic studies have
indicated a strong influence for Epstein-Barr virus (EBV)
infection, consumption of salt-preserved fish, exposure
to domestic wood cooking fires, and exposure to
occupational solvents in the risk for NPC[3,4]. Accumulating
data have shown that genetic polymorphisms of the
genes responsible for the xenobiotic enzymes which
metabolize carcinogenic compounds underlie individual
variations in cancer risk[5]. Most carcinogens undergo
activation by Phase I enzymes, often as an oxidation
reaction, and detoxification by Phase II enzymes.
CYP2E1 is a Phase I enzyme included in the
cytochrome P450 superfamily. CYP2E1 plays a major role in
the metabolic activation of nitrosamines. The RsaI
polymorphism of CYP2E1 (rs2031920) in the promoter
region has been reported to be associated with increased
risk of lung cancer and lymphomas[6,7]. Two studies
have associated this polymorphism with NPC
development[8,9]. Glutathione S-transferases (GSTs) are a
group of enzymes involved in Phase II detoxification of
carcinogens. GSTP1 is a major GST isoform. The Ile to
Val substitution at codon 105 of exon 5 variant in
GSTP1 (rs947894) has been investigated for associations
with breast and lung cancer in several studies[10,11].
Four of 22 studies showed a significantly higher risk for
head and neck cancers in persons with the Ile/Val and/
or Val/Val genotypes than in those with the Ile/Ile
genotypes[5].
NQO1 is an enzyme previously shown to detoxify a
number of natural and synthetic compounds and,
conversely, to activate certain anticancer agents[12]. A
single nucleotide polymorphism (SNP) C to T at position
609 (rs1800566) in the NQO1 coding region (replacing
proline with serine at codon 187) leads to lower enzyme
activity and has been shown to be associated with
increased risk of myeloid leukemia and bladder
carcinoma[12,13]. Myeloperoxidase (MPO) is an endogenous
oxidant enzyme that generates reactive oxygen species
(ROS). A single G-463A base transition in the MPO
promoter region was identified at the SP1 binding site,
which might mod (...truncated)