Analysis of Relation Between C677T Genotype in MTHFR Gene and Prostatic Cancer in Iranian Males
,
Abstract
Methylenetetrahydrofolate reductase (MTHFR) enzyme is one of the most important enzymes with a pivotal role in the folate metabolism and DNA synthesis pathways. Single nucleotide polymorphism (SNPs) in the coding gene has been related to many medical diseases as well as diverse malignancies including the prostate cancer which is the leading cause of the cancer deaths in men and one of the major public health problems. The goal of this study is to determine the relationship between the MTHFR C677T SNP and the prostate adenocarcinoma in Iranian males attending to the Labbafi-nezhad hospital in Tehran. In this Case-control unmatched study, 67 and 75 paraffinized tissue samples were taken out of the specimens diagnosed previously as the prostatic adenocarcinoma and nodular prostatic hyperplasia for the case and control groups respectively. MTHFR C677T genotyping was done by the use of multiplex ARMS-PCR and frequencies of the alleles were compared between the case and control groups as well as calculating the deviation from Hardy-Weinberg equilibrium and Odds Ratio for the "T" allele regarding the prostatic carcinoma. The observed rates in the control group were not too different from that of expected from Hardy-Weinberg equilibrium (P=0.407). Frequencies of the possible genotypes were as follows: CC, 43.28% vs. 42.67%; CT, 49.25% vs. 52% and CT, 7.46% vs. 5.33% in the case and control groups respectively (P=0.85). 1.37 times increased risk was found for the homozygote carriers of C677T variant (OR: 1.37, 95% CI: 0.33-5.6; P=0.653) which is however statistically not significant. No association has been evident between the MTHFR 677C>T polymorphism and the risk of prostatic carcinoma in this study confirming the findings of some of the previous attempts; however, (OR: 1.37, 95% CI: 0.33-5.6) implies a slight effect of the homozygote on the carcinogenesis. Thus larger studies especially with a greater number of the smaples are recommended.
Kang SS, Wong PW, Susmano A, Sora J, Norusis M, Ruggie N. Thermolabile methylenetetrahydrofolate reductase: an inherited risk factor for coronary arterydisease. Am J Hum Genet1991;48(3):536-45.
Taioli E, Garza MA, Ahn YO, Bishop DT, Bost J,Budai B, Chen K, Gemignani F, Keku T, Lima CS, Le Marchand L, Matsuo K, Moreno V, Plaschke J, Pufulete M, et al. Meta- and pooled analyses of the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and colorectal cancer: a HuGE-GSEC review. Am J Epidemiol 2009;170(10):1207-21.
Goyette P, Pai A, Milos R, Frosst P, Tran P, Chen Z, Chan M, Rozen R.Gene structure of human and mouse methylenetetrahydrofolate reductase (MTHFR). Mamm Genome 1998;9(8):652-6. Erratum in: Mamm Genome1999 Feb;10(2):204.
Sharp L, Little J. Polymorphisms in genes involved in folate metabolism and colorectal neoplasia: a HuGE review. Am J Epidemiol 2004;159(5):423-43.
Muslumanoglu MH, Tepeli E, Demir S, Uludag A, Uzun D, Atli E, Canturk KM, Ozdemir M, Turgut M.The analysis of the relationship between A1298C and C677T polymorphisms of the MTHFR gene with prostate cancer in Eskisehir population. Genet Test Mol Biomarkers 2009;13(5):641-5.
Wilcken B, Bamforth F, Li Z, Zhu H, Ritvanen A, Renlund M, Stoll C, Alembik Y, Dott B, Czeizel AE, Gelman-Kohan Z, Scarano G, Bianca S, Ettore G, Tenconi R, et al. Geographical and ethnic variation of the 677C>T allele of 5,10 methylenetetrahydrofolate reductase (MTHFR): findings from over 7000 newborns from 16 areas world wide. J Med Genet 2003;40(8):619-25.
Fard-Esfahani P, Fard-Esfahani A, Saidi P, Fayaz S, Mohabati R, Majdi M.An increased risk of differentiated thyroid carcinoma in Iran with the 677C→T homozygous polymorphism in the MTHFR Gene. Cancer Epidemiol 2011;35(1):56-8.
Trabetti E.Homocysteine, MTHFR gene polymorphisms, and cardio-cerebrovascular risk. J Appl Genet 2008;49(3):267-82.
Lin PT, Cheng CH, Wei JC, Huang YC.Low plasma pyridoxal 5'-phosphate concentration and MTHFR 677C-- >T genotypes are associated with increased risk of hypertension. Int J Vitam Nutr Res 2008;78(1):33-40.
Niu WQ, You YG, Qi Y. Strong association of methylenetetrahydrofolate reductase gene C677T polymorphism with hypertension and hypertension-inpregnancy in Chinese: a meta-analysis. J Hum Hypertens 2012;26(4):259-67.
Hill LD, York TP, Kusanovic JP, Gomez R, Eaves LJ, Romero R, Strauss JF 3rd.Epistasis between COMT and MTHFR in maternal-fetal dyads increases risk for preeclampsia. PLoS One 2011;6(1):e16681.
Sen S, Reddy PL, Grewal RP, Busby M, Chang P, Hinderliter A.Hyperhomocysteinemia is Associated with Aortic Atheroma Progression in Stroke/TIA Patients. Front Neurol 2010;1:131.
Dhar S, Chatterjee S, Ray S, Dutta A, Sengupta B, Chakrabarti S. Polymorphisms of methylenetetrahydrofolate reductase gene as the genetic predispositions of coronary artery diseases in eastern India. J Cardiovasc Dis Res 2010;1(3):152-7.
Wernimont SM, Raiszadeh F, Stover PJ, Rimm EB, Hunter DJ, Tang W, Cassano PA. Polymorphisms in serine hydroxymethyltransferase 1 and methylenetetrahydrofolate reductase interact to increase cardiovascular disease risk in humans. J Nutr 2011;141(2):255-60.
Chutinet A, Suwanwela NC, Snabboon T, Chaisinanunkul N, Furie KL, Phanthumchinda K. Association between genetic polymorphisms and sites of cervicocerebral artery atherosclerosis. J Stroke Cerebrovasc Dis 2012;21(5):379-85.
Alsayouf H, Zamel KM, Heyer GL, Khuhro AL, Kahwash SB, de los Reyes EC.Role of methylenetetrahydrofolate reductase gene (MTHFR) 677C>T polymorphism in pediatric cerebrovascular disorders. J Child Neurol 2011;26(3):318-21.
Kim SY, Park SY, Choi JW, Kim do J, Lee SY, Lim JH, Han JY, Ryu HM, Kim MH.Association between MTHFR 1298A>C polymorphism and spontaneous abortion with fetal chromosomal aneuploidy. Am J Reprod Immunol 2011;66(4):252-8.
Jeddi-Tehrani M, Torabi R, Zarnani AH, Mohammadzadeh A, Arefi S, Zeraati H, Akhondi MM, Chamani- Tabriz L, Idali F, Emami S, Zarei S.Analysis of plasminogen activator inhibitor-1, integrin beta3, beta fibrinogen, and methylenetetrahydrofolate reductase polymorphisms in Iranian women with recurrent pregnancy loss. Am J Reprod Immunol 2011;66(2):149-56.
Seremak-Mrozikiewicz A, Drews K, Kurzawinska G, Bogacz A, Grzeskowiak E, Mrozikiewicz PM.The significance of 1793G>A polymorphism in MTHFR gene in women with first trimester recurrent miscarriages. Neuro Endocrinol Lett 2010;31(5):717-23.
Blanton SH, Henry RR, Yuan Q, Mulliken JB, Stal S,Finnell RH, Hecht JT. Folate pathway and nonsyndromic cleft lip and palate. Birth Defects Res A Clin Mol Teratolv 2011;91(1):50-60.
Wang SS, Qiao FY, Feng L, Lv JJ. Polymorphisms in genes involved in folate metabolism as maternal risk factors for Down syndrome in China. J Zhejiang Univ Sci B 2008;9(2):93-9.
Sadiq MF, Al-Refai EA, Al-Nasser A, Khassawneh M, Al- Batayneh Q. Methylenetetrahydrofolate reductase polymorphisms C677T and A1298C as maternal risk factors for Down syndrome in Jordan. Genet Test Mol Biomarkers 2011;15(1-2):51-7.
Trabetti E. Homocysteine, MTHFR gene polymorphisms, and cardio-cerebrovascular risk. J Appl Genet 2008;49(3):267-82.
Mavros M, Chiriţă V, Popescu O, Ferencz B. The genetic polymorphism of MTHFR gene in schizophrenia. Rev Med Chir Soc Med Nat Iasi 2008;112(1):76-82.
Golimbet VE, Panteleeva GP, Bologov PV, Korovaĭtseva GI, Abramova LI. Molecular-genetic approach to the clinical and nosologic differentiation of schizoaffective disorder. Zh Nevrol Psikhiatr Im S S Korsakova 2010;110(10):48-52.
Hill M, Shannahan K, Jasinski S, Macklin EA, Raeke L, Roffman JL, Goff DC. Folate supplementation in schizophrenia: a possible role for MTHFR genotype. Schizophr Res 2011;127(1-3):41-5.
Saetre P, Vares M, Werge T, Andreassen OA, Arinami T, Ishiguro H, Nanko S, Tan EC, Han DH, Roffman JL, Muntjewerff JW, Jagodzinski PP, Kempisty B, Hauser J, Vilella E, et al. Methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C polymorphisms and age of onset in schizophrenia: a combined analysis of independent samples. Am J Med Genet B Neuropsychiatr Genet 2011;156(2):215-24.
Lin L, Guo XZ, Li M. Analysis on relationship of Chinese medicine syndrome pattern with urinary albumin excretion rate and its related factors in early stage diabetic nephropathy. Zhongguo Zhong Xi Yi Jie He Za Zhi 2010;30(9):912-4.
Rahimi M, Hasanvand A, Rahimi Z, Vaisi-Raygani A, Mozafari H, Rezaei M, Zargooshi J, Najafi F, Shakiba E. Synergistic effects of the MTHFR C677T and A1298C polymorphisms on the increased risk of micro- and macroalbuminuria and progression of diabetic nephropathy among Iranians with type 2 diabetes mellitus. Clin Biochem 2010;43(16-17):1333-9.
Vasilopoulos Y, Sarafidou T, Bagiatis V, Skriapa L, Goutzelas Y, Pervanidou P, Lazopoulou N, Chrousos GP, Mamuris Z. Association between polymorphisms in MTHFR and APOA5 and metabolic syndrome in the Greek population. Genet Test Mol Biomarkers 2011;15(9):613-7.
Gromadzka G, Rudnicka M, Chabik G, Przybyłkowski A, Członkowska A. Genetic variability in the methylenetetrahydrofolate reductase gene (MTHFR) affects clinical expression of Wilson's disease. J Hepatol 2011;55(4):913-9.
Moon HW, Kim TY, Oh BR, Min HC, Cho HI, Bang SM, Lee JH, Yoon SS, Lee DS. MTHFR 677CC/1298CC genotypes are highly associated with chronic myelogenous leukemia: a case-control study in Korea. Leuk Res 2007;31(9):1213-7.
Karas Kuzelicki N, Milek M, Jazbec J, Mlinaric-Rascan I. 5,10-Methylenetetrahydrofolate reductase (MTHFR) low activity genotypes reduce the risk of relapse-related acute lymphoblastic leukemia (ALL). Leuk Res 2009;33(10):1344-8.
Larsson SC, Giovannucci E, Wolk A. Folate intake, MTHFR polymorphisms, and risk of esophageal, gastric, and pancreatic cancer: a meta-analysis. Gastroenterology 2006;131(4):1271-83.
Etienne-Grimaldi MC, Francoual M, Formento JL, MilanoG. Methylenetetrahydrofolate reductase (MTHFR) variants and fluorouracil-based treatments in colorectal cancer. Pharmacogenomics 2007;8(11):1561-6.
Vossen CY, Hoffmeister M, Chang-Claude JC, Rosendaal FR, Brenner H. Clotting factor gene polymorphisms and colorectal cancer risk. J Clin Oncol= 2011;29(13):1722-7.
Kwak SY, Kim UK, Cho HJ, Lee HK, Kim HJ, Kim NK, Hwang SG. Methylenetetrahydrofolate reductase (MTHFR) and methionine synthase reductase (MTRR) gene polymorphisms as risk factors for hepatocellular carcinoma in a Korean population. Anticancer Res 2008;28(5A):2807-11.
Mazaki T, Masuda H, Takayama T. Polymorphisms and pancreatic cancer risk: a meta-analysis. Eur J Cancer Prev 2011;20(3):169-83.
Reljic A, Simundic AM, Topic E, Nikolac N, Justinic D,Stefanovic M. The methylenetetrahydrofolate reductase(MTHFR) C677T polymorphism and cancer risk: the Croatian case-control study. Clin Biochem 2007;40(13-14):981-5.
Cui LH, Shin MH, Kim HN, Song HR, Piao JM, Kweon SS, Choi JS, Yun WJ, Kim YC, Oh IJ, Kim KS. Methylenetetrahydrofolate reductase C677T polymorphism in patients with lung cancer in a Korean population. BMC Med Genet 2011;12:28.
Kang SY, Lee SJ, Hong SH, Chung YK, Oh HS, Kim SW, Yim DJ, Kim NK. Polymorphisms of 5,10- methylenetetrahydrofolate reductase and thymidylate synthase in squamous cell carcinoma and basal cell carcinoma of the skin. Mol Med Report 2010;3(5):741-7.
Terry KL, Tworoger SS, Goode EL, Gates MA, Titus- Ernstoff L, Kelemen LE, Sellers TA, Hankinson SE, Cramer DW. MTHFR polymorphisms in relation to ovarian cancer risk. Gynecol Oncol 2010;119(2):319-24.
Chang SC, Yang YC, Zhang ZF. Single nucleotide polymorphisms in genes of one-carbon metabolism pathway and bladder cancer survival. Cancer Epidemoil Biomarkers Prev 2011;20(4):716-7.
Ye S, Dhillon S, Ke X, Collins AR, Day IN. An efficient procedure for genotyping single nucleotide polymorphisms. Nucleic Acids Res 2001;29(17):E88-8.
Faure-Delanef L, Quéré I, Chassé JF, Guerassimenko O, Lesaulnier M, Bellet H, Zittoun J, Kamoun P, Cohen D. Methylenetetrahydrofolate reductase thermolabile variant and human longevity. Am J Hum Genet 1997;60(4):999-1001.
Wang J, Shete S. A test for genetic association that incorporates information about deviation from Hardy- Weinberg proportions in cases. Am J Hum Genet 2008;83(1):53-63.
Kimura F, Franke KH, Steinhoff C, Golka K, Roemer HC, Anastasiadis AG, Schulz WA. Methyl group metabolism gene polymorphisms and susceptibility to prostatic carcinoma. Prostate 2000;45(3):225-31.
Cicek MS, Nock NL, Li L, Conti DV, Casey G, Witte JS.Relationship between methylenetetrahydrofolate reductase C677T and A1298C genotypes and haplotypes and prostate cancer risk and aggressiveness. Cancer EpidemiolBiomarkers Prev 2004;13(8):1331-6.
Johansson M, Van Guelpen B, Hultdin J, Wiklund F, Adami HO, Bälter K, Grönberg H, Stattin P. The MTHFR 677C --> T polymorphism and risk of prostate cancer: results from the CAPS study. Cancer Causes Control 2007;18(10):1169-74.
Bai JL, Zheng MH, Xia X, Ter-Minassian M, Chen YP,Chen F. MTHFR C677T polymorphism contributes to prostate cancer risk among Caucasians: A meta-analysis of 3511 cases and 2762 controls. Eur J Cancer2009;45(8):1443-9.
Collin SM, Metcalfe C, Zuccolo L, Lewis SJ, Chen L, Cox A, Davis M, Lane JA, Donovan J, Smith GD, Neal DE, Hamdy FC, Gudmundsson J, Sulem P, Rafnar T, et al.Association of folate-pathway gene polymorphisms withthe risk of prostate cancer: a population-based nested casecontrolstudy, systematic review, and meta-analysis. Cancer Epidemiol Biomarkers Prev 2009;18(9):2528-39.
Marchal C, Redondo M, Reyes-Engel A, Perea-Milla E, Gaitan MJ, Machuca J, Diaz F, Caballero J, Carnero J.Association between polymorphisms of folatemetabolizing enzymes and risk of prostate cancer. Eur JSurg Oncol 2008;34(7):805-10.
Safarinejad MR, Shafiei N, Safarinejad S. Relationshipbetween three polymorphisms of methylenetetrahydrofolate reductase (MTHFR C677T, A1298C, and G1793A) gene and risk of prostate cancer: a case-control study. Prostate 2010;70(15):1645-57.
Wu HC, Chang CH, Tsai RY, Lin CH, Wang RF, Tsai CW, Chen KB, Yao CH, Chiu CF, Bau DT, Lin CC. Significant association of methylenetetrahydrofolate reductase single nucleotide polymorphisms with prostate cancer susceptibility in taiwan. Anticancer Res 2010;30(9):3573-7.
| Files | ||
| Issue | Vol 50, No 10 (2012) | |
| Section | Original Article(s) | |
| Keywords | ||
| MTHFR Polymorphism Prostatic carcinoma | ||
| Rights and permissions | |
|
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. |
