PMID- 19465161 OWN - NLM STAT- MEDLINE DCOM- 20091106 LR - 20231213 IS - 1567-7257 (Electronic) IS - 1567-1348 (Linking) VI - 9 IP - 5 DP - 2009 Sep TI - Single nucleotide polymorphism in DNMT3B promoter and its association with hepatocellular carcinoma in a Moroccan population. PG - 877-81 LID - 10.1016/j.meegid.2009.05.012 [doi] AB - Hepatocellular carcinoma is a major malignant tumor characterized in all areas by the disparity of risk between genders. The molecular bases of such disparity are still poorly understood. DNA-methyltransferase-3B (DNMT3B) may play an oncogenic role during tumorigenesis, and its genetic variants have been consistently associated with risk of several cancers, but a single study has investigated their roles in hepatocellular carcinoma (HCC). Polymorphisms of the DNMT3B gene may influence its activity on DNA methylation in several cancers, thereby modulating susceptibility to tumorigenesis. To test this hypothesis, we investigated the association between single nucleotide polymorphism -149C>T (rs2424913) in the promoter region DNMT3B and risk of HCC in a Moroccan population. In this case-control study, the DNMT3B SNP was genotyped by polymerase chain reaction-restriction fragment length polymorphism in 96 HCCs patients and 222 healthy controls that matched for age, sex and ethnicity. Overall, we found that, the DNMT3B 149 TT genotype was not significantly associated with increased risk of HCC (adjusted odds ratio (OR), 0.86, 95% CI, 0.41-1.80, P=0.697). Stratification analysis detected, however, a trend towards a profound risk in the female subset of patients (OR=2.04, 95% CI, 0.77-5.42) and a lesser risk for HCV-infected patients (OR=1.33, 95% CI, 0.43-4.17). Our findings contrast with those of previous studies performed in various cancers, which showed that individuals carrying at least one T allele have a significantly increased risk of developing cancer. In addition, we provide genetic evidence for the major difference of HCC risk between men and women. Further mechanistic studies are needed to unravel the underlying molecular mechanisms. FAU - Ezzikouri, Sayeh AU - Ezzikouri S AD - Laboratoire des Hepatites Virales, Institut Pasteur du Maroc 1, Place Louis Pasteur, 20100 Casablanca, Morocco. sayeh.ezzikouri@pasteur.ma FAU - El Feydi, Abdellah Essaid AU - El Feydi AE FAU - Benazzouz, Mustapha AU - Benazzouz M FAU - Afifi, Rajae AU - Afifi R FAU - El Kihal, Latifa AU - El Kihal L FAU - Hassar, Mohammed AU - Hassar M FAU - Akil, Abdellah AU - Akil A FAU - Pineau, Pascal AU - Pineau P FAU - Benjelloun, Soumaya AU - Benjelloun S LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20090522 PL - Netherlands TA - Infect Genet Evol JT - Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases JID - 101084138 RN - EC 2.1.1.37 (DNA (Cytosine-5-)-Methyltransferases) SB - IM MH - Adult MH - Aged MH - Aged, 80 and over MH - Carcinoma, Hepatocellular/enzymology/epidemiology/*genetics MH - Chi-Square Distribution MH - DNA (Cytosine-5-)-Methyltransferases/*genetics MH - Female MH - Genetic Predisposition to Disease MH - Humans MH - Liver Neoplasms/enzymology/epidemiology/*genetics MH - Logistic Models MH - Male MH - Middle Aged MH - Morocco/epidemiology MH - Polymorphism, Single Nucleotide MH - Promoter Regions, Genetic MH - Risk Factors MH - DNA Methyltransferase 3B EDAT- 2009/05/26 09:00 MHDA- 2009/11/07 06:00 CRDT- 2009/05/26 09:00 PHST- 2009/03/03 00:00 [received] PHST- 2009/05/14 00:00 [revised] PHST- 2009/05/15 00:00 [accepted] PHST- 2009/05/26 09:00 [entrez] PHST- 2009/05/26 09:00 [pubmed] PHST- 2009/11/07 06:00 [medline] AID - S1567-1348(09)00127-0 [pii] AID - 10.1016/j.meegid.2009.05.012 [doi] PST - ppublish SO - Infect Genet Evol. 2009 Sep;9(5):877-81. doi: 10.1016/j.meegid.2009.05.012. Epub 2009 May 22.