Browse > Article
http://dx.doi.org/10.7314/APJCP.2015.16.10.4457

Paraoxonase 1 (PON1) Q192R Gene Polymorphism and Cancer Risk: A Meta-Analysis Based on 30 Publications  

Zhang, Meng (Shenzhen Second People's Hospital, clinical medicine college of Anhui Medical University)
Xiong, Hu (The second Hospital of Lanzhou University)
Fang, Lu (The second affiliated hospital of Anhui Medical University)
Lu, Wei (Shenzhen Second People's Hospital, clinical medicine college of Anhui Medical University)
Wu, Xun (Department of Anatomy, School of Basic Medicine Science, Southern Medical University)
Huang, Zhan-Sen (Zhongshan School of Medicine, Sun Yat-sen University)
Wang, Yong-Qiang (Shenzhen Second People's Hospital, clinical medicine college of Anhui Medical University)
Cai, Zhi-Ming (Shenzhen Second People's Hospital, clinical medicine college of Anhui Medical University)
Wu, Song (Shenzhen Second People's Hospital, clinical medicine college of Anhui Medical University)
Publication Information
Asian Pacific Journal of Cancer Prevention / v.16, no.10, 2015 , pp. 4457-4463 More about this Journal
Abstract
Common genetic variation Q192R in the paraoxonase 1 (PON1) gene has been considered to be implicated in the development of many cancers. Nevertheless, results from the related studies were inconsistent. To elucidate the association, we performed a meta-analysis for 8,112 cases and 10,037 controls from 32 published case-control studies. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of the association by STATA 12.0 software. Overall, we revealed that the PON1-192R allele was associated with a reduced risk of the overall cancers. Moreover, in the stratified analysis by cancer types (breast cancer, prostate cancer, brain cancer etc.), the results showed that PON1-192R allele was associated with a decreased risk in breast cancer (R vs Q: OR=0.605, 95% CI=0.378-0.967, $P_{heterogeneity}=0.000$; RR vs QQ: OR=0.494, 95% CI=0.275-0.888, $P_{heterogeneity}=0.002$; RQ vs QQ: OR=0.465, 95% CI=0.259-0.835, $P_{heterogeneity}=0.000$; and RR+RQ vs QQ: OR=0.485, 95% CI=0.274-0.857, $P_{heterogeneity}=0.000$), and associated with prostate cancer in homozygote (RR vs QQ: OR=0.475, 95% CI=0.251-0.897, $P_{heterogeneity}=0.001$) and recessive models (RR vs RQ+QQ: OR=0.379, 95% CI=0.169-0.853, $P_{heterogeneity}=0.000$), while an increased risk was identified in lymphoma (R vs Q: OR=1.537, 95% CI=1.246-1.896, $P_{heterogeneity}=0.944$; RR vs QQ: OR=2.987, 95% CI=1.861-4.795, $P_{heterogeneity}=0.350$; RR+RQ vs QQ: OR=1.354, 95% CI=1.021-1.796, $P_{heterogeneity}=0.824$; and RR vs RQ+QQ: OR=2.934, 95% CI=1.869-4.605, $P_{heterogeneity}=0.433$), and an increased risk in prostate cancer under heterozygote comparison (RQ vs QQ: OR=1.782, 95% CI=1.077-2.950, $P_{heterogeneity}=0.000$) and dominant models (RR+RQ vs QQ: OR=1.281, 95% CI=1.044-1.573, $P_{heterogeneity}=0.056$). When subgroup analysis that performed by the control source (hospital based or population based), a decreased risk of the overall cancers was revealed by homozygote (RR vs QQ: OR=0.601, 95% CI=0.366-0.987, $P_{heterogeneity}=0.000$) and dominant models (RR vs RQ+QQ: OR= 0.611, 95% CI=0.384-0.973, $P_{heterogeneity}=0.000$) in hospital based group. Stratifying by ethnicity, a significantly reduced risk of the overall cancers under allele contrast model (R vs Q: OR=0.788, 95% CI=0.626-0.993, $P_{heterogeneity}=0.000$) was uncovered in Caucasian. In summary, these findings suggested that PON1 Q192R polymorphism was associated with a reduced risk of the overall cancers, nevertheless, it might increase cancer susceptibility of prostate and lymphoma risk. Large well-designed epidemiological studies will be continued on this issue of interest.
Keywords
Paraoxonase 1; Q192R; polymorphism; cancer; meta-analysis;
Citations & Related Records
Times Cited By KSCI : 3  (Citation Analysis)
연도 인용수 순위
1 Li WF, Costa LG, Richter RJ, et al (2000). Catalytic efficiency determines the in-vivo efficacy of PON1 for detoxifying organophosphorus compounds. Pharmacogenetics, 10, 767-79.   DOI
2 Lincz LF, Kerridge I, Scorgie FE, et al (2004). Xenobiotic gene polymorphisms and susceptibility to multiple myeloma. Haematologica, 89, 628-9.
3 Lurie G, Wilkens LR, Thompson PJ, et al (2008). Genetic polymorphisms in the Paraoxonase 1 gene and risk of ovarian epithelial carcinoma. Cancer Epidemiol Biomarkers Prev, 17, 2070-7.   DOI
4 Mackness B, Mackness MI, Arrol S, et al (1997). Effect of the molecular polymorphisms of human paraoxonase (PON1) on the rate of hydrolysis of paraoxon. Br J Pharmacol, 122, 265-8.   DOI
5 Martinez C, Molina JA, Alonso-Navarro H, et al (2010). Two common nonsynonymous paraoxonase 1 (PON1) gene polymorphisms and brain astrocytoma and meningioma. BMC Neurol, 10, 71.   DOI
6 Naidu R, Har YC, Taib NA (2010). Genetic polymorphisms of paraoxonase 1 (PON1) gene: association between L55M or Q192R with breast cancer risk and clinico-pathological parameters. Pathol Oncol Res, [Epub ahead of print].
7 Ozturk O, Kagnici OF, Ozturk T, et al (2009). 192R allele of paraoxanase 1 (PON1) gene as a new marker for susceptibility to bladder cancer. Anticancer Res, 29, 4041-6.
8 Pharoah PD, Dunning AM, Ponder BA, et al (2004). Association studies for finding cancer-susceptibility genetic variants. Nat Rev Cancer, 4, 850-60.   DOI
9 Rajaraman P, Hutchinson A, Rothman N, et al (2008). Oxidative response gene polymorphisms and risk of adult brain tumors. Neuro Oncol, 10, 709-15.   DOI
10 Searles Nielsen S, Mueller BA, De Roos AJ, et al (2005). Risk of brain tumors in children and susceptibility to organophosphorus insecticides: the potential role of paraoxonase (PON1). Environ Health Perspect, 113, 909-13.   DOI
11 Stevens VL, Rodriguez C, Talbot JT, et al (2008). Paraoxonase 1 (PON1) polymorphisms and prostate cancer in the CPS-II nutrition cohort. Prostate, 68, 1336-40.   DOI
12 Sun Y (1990). Free radicals, antioxidant enzymes, and carcinogenesis. Free Radic Biol Med, 8, 583-99.   DOI
13 Tobias A, Campbell MJ (1999). Modelling influenza epidemics in the relation between black smoke and total mortality. A sensitivity analysis. J Epidemiol Community Health, 53, 583-4.   DOI
14 Torre LA, Bray F, Siegel RL, et al (2015). Global cancer statistics, 2012. CA Cancer J Clin, 65, 87-108.   DOI
15 Uyar OA, Kara M, Erol D, et al (2011). Investigating paraoxonase-1 gene Q192R and L55M polymorphism in patients with renal cell cancer. Genet Mol Res, 10, 133-9.   DOI
16 Van Der Logt EM, Janssen CH, Van Hooijdonk Z, et al (2005). No association between genetic polymorphisms in NAD(P) H oxidase p22phox and paraoxonase 1 and colorectal cancer risk. Anticancer Res, 25, 1465-70.
17 Vasconcelos GM, Goncalves BA, Montalvao-de-Azevedo R, et al (2014). PON1 Q192R polymorphism (rs662) is associated with childhood embryonal tumors. Mol Biol Rep, 41, 6111-5.   DOI
18 Vecka M, Jachymova M, Vavrova L, et al (2012). Paraoxonase-1 (PON1) status in pancreatic cancer: relation to clinical parameters. Folia Biol (Praha), 58, 231-7.
19 Zamora-Ros R, Rothwell JA, Scalbert A, et al (2013). Dietary intakes and food sources of phenolic acids in the European Prospective Investigation into cancer and nutrition (EPIC) study. Br J Nutr, 110, 1500-11.   DOI   ScienceOn
20 Wang H, Li L, Ding L, et al (2012). Association of genetic polymorphisms in the paraoxonase 1 gene with the risk and prognosis of non-small cell lung cancer in Chinese Han population. J Investig Med, 60, 592-7.   DOI
21 Zhao P, Zhao L, Zou P, et al (2012). Genetic oxidative stress variants and glioma risk in a Chinese population: a hospitalbased case-control study. BMC Cancer, 12, 617.   DOI
22 Ames BN (1983). Dietary carcinogens and anticarcinogens. Oxygen radicals and degenerative diseases. Science, 221, 1256-64.   DOI
23 Ahmed NS, Shafik NM, Elraheem OA, et al (2015). Association of paraoxonase-1(Q192R and L55M) gene polymorphisms and activity with colorectal cancer and effect of surgical intervention. Asian Pac J Cancer Prev, 16, 803-9.   DOI
24 Akcay MN, Polat MF, Yilmaz I, et al (2003a). Serum paraoxonase levels in pancreatic cancer. Hepatogastroenterology, 50, ccxxv-ccxxvii.
25 Akcay MN, Yilmaz I, Polat MF, et al (2003b). Serum paraoxonase levels in gastric cancer. Hepatogastroenterology, 50, cclxxiii-cclxxv.
26 Akkiz H, Kuran S, Akgollu E, et al (2013). Effect of PON1 gene polymorphisms in Turkish patients with hepatocellular carcinoma. Meta Gene, 1, 93-101.   DOI
27 Aksoy-Sagirli P, Cakmakoglu B, Isbir T, et al (2011). Paraoxonase-1 192/55 polymorphisms and the risk of lung cancer in a Turkish population. Anticancer Res, 31, 2225-9.
28 Antognelli C, Del Buono C, Ludovini V, et al (2009). CYP17, GSTP1, PON1 and GLO1 gene polymorphisms as risk factors for breast cancer: an Italian case-control study. BMC Cancer, 9, 115.   DOI
29 Antognelli C, Mearini L, Talesa VN, et al (2005). Association of CYP17, GSTP1, and PON1 polymorphisms with the risk of prostate cancer. Prostate, 63, 240-51.   DOI
30 Antognelli C, Mezzasoma L, Mearini E, et al (2013). Glyoxalase 1-419C>A variant is associated with oxidative stress: implications in prostate cancer progression. PLoS One, 8, 74014.   DOI
31 Arpaci A, Gormus U, Dalan B, et al (2009). Investigation of PON1 192 and PON1 55 polymorphisms in ovarian cancer patients in Turkish population. In Vivo, 23, 421-4.
32 Begg CB, Mazumdar M (1994). Operating characteristics of a rank correlation test for publication bias. Biometrics, 50, 1088-101.   DOI
33 Bredberg A (2011). Cancer: more of polygenic disease and less of multiple mutations? A quantitative viewpoint. Cancer, 117, 440-5.   DOI
34 Cejas P, Casado E, Belda-Iniesta C, et al (2004). Implications of oxidative stress and cell membrane lipid peroxidation in human cancer (Spain). Cancer Causes Control, 15, 707-19.   DOI
35 Delimaris I, Faviou E, Antonakos G, et al (2007). Oxidized LDL, serum oxidizability and serum lipid levels in patients with breast or ovarian cancer. Clin Biochem, 40, 1129-34.   DOI
36 Conesa-Zamora P, Ruiz-Cosano J, Torres-Moreno D, et al (2013). Polymorphisms in xenobiotic metabolizing genes (EPHX1, NQO1 and PON1) in lymphoma susceptibility: a case control study. BMC Cancer, 13, 228.   DOI
37 Davies HG, Richter RJ, Keifer M, et al (1996). The effect of the human serum paraoxonase polymorphism is reversed with diazoxon, soman and sarin. Nat Genet, 14, 334-6.   DOI
38 de Aguiar Goncalves BA, Vasconcelos GM, Thuler LC, et al (2012). NQO1 rs1800566 (C609T), PON1 rs662 (Q192R), and PON1 rs854560 (L55M) polymorphisms segregate the risk of childhood acute leukemias according to age range distribution. Cancer Causes Control, 23, 1811-9.   DOI
39 DerSimonian R, Laird N (1986). Meta-analysis in clinical trials. Control Clin Trials, 7, 177-88.   DOI
40 Egger M, Davey Smith G, Schneider M, et al (1997). Bias in meta-analysis detected by a simple, graphical test. BMJ, 315, 629-34.   DOI
41 Elkiran ET, Mar N, Aygen B, et al (2007). Serum paraoxonase and arylesterase activities in patients with lung cancer in a Turkish population. BMC Cancer, 7, 48.   DOI
42 Ellidag HY, Aydin O, Eren E, et al (2014). Decreased HDLdependent paraoxonase and arylesterase enzyme activity may indicate a worse prognosis in multiple myeloma. Asian Pac J Cancer Prev, 15, 9847-51.   DOI
43 Eom SY, Yim DH, Lee CH, et al (2015). Interactions between paraoxonase 1 genetic polymorphisms and smoking and their effects on oxidative stress and lung cancer risk in a Korean Population. PLoS One, 10, 119100.
44 Hussein YM, Gharib AF, Etewa RL, et al (2011). Association of L55M and Q192R polymorphisms in paraoxonase 1 (PON1) gene with breast cancer risk and their clinical significance. Mol Cell Biochem, 351, 117-23.   DOI
45 Ergen A, Kilicoglu O, Ozger H, et al (2011). Paraoxonase 1 192 and 55 polymorphisms in osteosarcoma. Mol Biol Rep, 38, 4181-4.   DOI
46 Gallicchio L, McSorley MA, Newschaffer CJ, et al (2007). Body mass, polymorphisms in obesity-related genes, and the risk of developing breast cancer among women with benign breast disease. Cancer Detect Prev, 31, 95-101.   DOI
47 Humbert R, Adler DA, Disteche CM, et al (1993). The molecular basis of the human serum paraoxonase activity polymorphism. Nat Genet, 3, 73-6.   DOI
48 Kafadar AM, Ergen A, Zeybek U, et al (2006). Paraoxonase 192 gene polymorphism and serum paraoxonase activity in high grade gliomas and meningiomas. Cell Biochem Funct, 24, 455-60.   DOI
49 Karaman E, Uzun H, Papila I, et al (2010). Serum paraoxonase activity and oxidative DNA damage in patients with laryngeal squamous cell carcinoma. J Craniofac Surg, 21, 1745-9.   DOI
50 Kerridge I, Lincz L, Scorgie F, et al (2002). Association between xenobiotic gene polymorphisms and non-Hodgkin’s lymphoma risk. Br J Haematol, 118, 477-81.   DOI
51 Kokouva M, Koureas M, Dardiotis E, et al (2013). Relationship between the paraoxonase 1 (PON1) M55L and Q192R polymorphisms and lymphohaematopoietic cancers in a Greek agricultural population. Toxicology, 307, 12-6.   DOI
52 Lee CH, Lee KY, Choe KH, et al (2005). Effects of oxidative DNA damage induced by polycyclic aromatic hydrocarbons and genetic polymorphism of the paraoxonase-1 (PON1) gene on lung cancer. J Prev Med Public Health, 38, 345-50.