Methylenetetrahydrofolate reductase (MTHFR) C677T and thymidylate synthase promoter (TSER) polymorphisms in Indonesian children with and without leukemia

Giovannetti, Elisa; Ugrasena, Dewa G.; Supriyadi, Eddy; Vroling, Laura; Azzarello, A.; Lange, Desiree De; Peters, Godefridus J.; Veerman, A. J. P.; Cloos, Jacqueline

doi:10.1016/j.leukres.2007.02.011

Cited by 41 publications

(26 citation statements)

References 25 publications

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“…The prevalence of TS 3R/3R has been reported to be 33.1% in Caucasian children with ALL, while in Indonesian samples, its frequency reached 76.1% in ALL children (Giovannetti et al, 2008). Furthermore, the frequency of TS genotypes in the Indonesian ALL patients and controls did not show any significant difference (Giovannetti et al, 2008). In the study of Skibola et al (2002), individuals with TS 2R/3R were shown to exhibit a 2.8-fold reduction and those with TS 3R/3R exhibited a 4.0-fold reduction in ALL risk.…”

Section: Discussionmentioning

confidence: 94%

“…It has been shown that the ethnicity of an individual plays a role in the various distributions of polymorphisms of the genes involved in folate metabolism (Lima et al, 2008;Giovannetti et al, 2008). The prevalence of TS 3R/3R has been reported to be 33.1% in Caucasian children with ALL, while in Indonesian samples, its frequency reached 76.1% in ALL children (Giovannetti et al, 2008).…”

Section: Discussionmentioning

confidence: 99%

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Thymidylate synthase enhancer region polymorphism not related to susceptibility to acute lymphoblastic leukemia in the Kashmir population

Nazki

Masood²,

Banday³

et al. 2012

Genet. Mol. Res.

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ABSTRACT. Thymidylate synthase (TS) is a crucial enzyme in folate metabolism and plays a vital role in DNA synthesis and repair. The most common polymorphism in TS is a unique double (2R) or triple (3R) 28-bp tandem repeat sequence in the enhancer region of the TS gene (TSER). This genetic variation in TSER has been widely investigated and has been implicated as a risk factor for the development of various cancers, including acute lymphoblastic leukemia. It has also been found to influence sensitivity to anti-cancer drugs, such as methotrexate. We evaluated this polymorphism in acute lymphoblastic leukemia patients in the Kashmir population. In order to determine whether a double (2R2R) versus a triple (3R3R) 28-bp tandem repeat in the TSER modulates risk for acute lymphoblastic leukemia, 72 acute lymphoblastic leukemia cases and 144 age and gender matched, unrelated healthy individuals from the Kashmir region of India were evaluated for this polymorphism by PCR and direct sequencing. We found the frequency of the TS 2R allele to be 32.6 and 26.0%, in cases and controls, respectively. The TS 2R/2R genotype was found to be present in 15.27% of the cases TSER polymorphism and susceptibility to ALL and 9.72% of the controls, the 2R/3R variant in 34.72% of the cases and 32.63% of the controls, and the 3R/3R genotype in 50.0% of the cases and 57.63% of the controls. There was a significant association between the TS 2R/2R genotype and gender of acute lymphoblastic leukemia patients with males harboring the 2R/2R genotype exhibiting a higher risk of developing acute lymphoblastic leukemia than females (P = 0.009) We concluded that the TSER polymorphism appears not to be a risk factor for susceptibility to acute lymphoblastic leukemia in the Kashmir population.

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Section: Discussionmentioning

confidence: 94%

Section: Discussionmentioning

confidence: 99%

Thymidylate synthase enhancer region polymorphism not related to susceptibility to acute lymphoblastic leukemia in the Kashmir population

Nazki

Masood²,

Banday³

et al. 2012

Genet. Mol. Res.

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“…Pooling data from the 17 studies 29,33,[38][39][40][41][42][43][44][45][46][47][48][49][50][51] which have examined MTHFR C677T provided no evidence for a relationship between genotype and risk ( Table 2; Online Supplementary Figure S1; Online Supplementary Table S2). There was evidence of population stratification in the studies reported by Wiemels et al 38 and Balta et al, 40 as controls showed evidence of departure from HWE (P=0.02, 0.05).…”

Section: Meta-analysismentioning

confidence: 99%

“…The four studies 42,43,47,52 of the TS 2R>3R provide no evidence for a relationship between this polymorphism and ALL risk (Table 2; Online Supplementary Figure S1; Online Supplementary Table S2).…”

Section: Meta-analysismentioning

confidence: 99%

Candidate gene association studies and risk of childhood acute lymphoblastic leukemia: a systematic review and meta-analysis

Vijayakrishnan¹,

Houlston²

2010

Haematologica

111

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To evaluate the contribution of candidate gene association studies to the understanding of genetic susceptibility to childhood acute lymphoblastic leukemia we conducted a systematic review and meta-analysis of published studies (January 1996-July 2009. Studies had to meet the following criteria: be case-control design, be studied by two or more studies, not be focused on HLA antigen genetic markers and be published in English. We identified 47 studies of polymorphic variation in 16 genes and acute lymphoblastic leukemia risk. To clarify the impact of individual polymorphisms on risk, pooled analyses were performed. Of the 25 polymorphic variants studied, significant associations (P<0.05) were seen in pooled analyses for eight variants: GSTM1 (OR =1.16; 95%CI: 1.04-1.30), MTRR A66G (OR=0.73, 95%CI:0.59-0.91), SHMT1 C1420T (OR=0.79, 95%CI: 0.65-0.98), RFC1 G80A (OR=1.37, 95%CI: 1.11-1.69), CYP1A1*2A (OR=1.36, 95%CI:1.11-1.66), CYP2E1*5B (OR=1.99, 95%CI:1.32-3.00) NQO1 C609T (OR=1.24, 95%CI:1.02-1.50) and XRCC1 G28152A (OR=1.78, 95%CI:1.32-2.42). These findings should, however, be interpreted with caution as the estimated false-positive report probabilities (FPRP) for each association were not noteworthy (i.e. FPRP>0.2). While candidate gene analyses are complementary to genome-wide association studies, future analyses should be based on sample sizes commensurate with the detection of small effects and attention needs to be paid to study design.Key words: polymorphisms, acute lymphoblastic leukemia, risk, meta-analysis, false positive report probabilities. -analysis. Haematologica 2010;95(8):1405-1414. doi:10.3324/haematol.2010 This is an open-access paper. Citation: Vijayakrishnan J and Houlston RS. Candidate gene association studies and risk of childhood acute lymphoblastic leukemia: a systematic review and meta IntroductionAcute leukemia is the major pediatric cancer in developed countries, affecting between 30-45 per 1,000,000 children each year.1 Dysregulated immune response to infection may be a cause of childhood acute lymphoblastic leukemia (ALL) 2 and epidemiological data are consistent with transplacental carcinogen exposure as a basis for infant leukemia associated with MLL gene fusion, 3 but the role of environmental carcinogenesis in ALL is currently undefined. It is, however, likely that the risk of ALL from environmental exposure is influenced by co-inheritance of multiple low-risk variants.The commonest method for identifying common low-risk variants is through association studies. These are based on comparing the frequency of polymorphic genotypes in cases and controls. Alleles positively associated with the disease are analogous to risk factors in epidemiology and may be causally related to disease risk or in linkage disequilibrium with disease-causing variants. There are a number of different methods of analyzing the risk associated with a specific variant. For simple bi-allelic polymorphisms, the odds ratio of disease can be derived by comparing allele frequencies in cases and controls. This ap...

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“…Most of the studies had bigger cohort than ours, but Li and colleagues included 98 patients in their study and found that risk of ALL with the 1298C allele carriers (AC+CC) was elevated by 1.1 times compared with AA genotype (Li et al, 2014). Giovannetti et al showed in their study ethnic differences in polymorphisms (Giovannetti et al, 2008). There are publications about several meta-analyses focused on the associations between MTHFR C677T and A1298C polymorphisms and ALL risk.…”

Section: Discussionmentioning

confidence: 75%

Lack of Association between Polymorphisms in Genes MTHFR and MDR1 with Risk of Childhood Acute Lymphoblastic Leukemia

Kreile¹,

Rots²,

Piekuse³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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Background: Acute lymphoblastic leukemia (ALL) is a complex disease caused by interactions between hazardous exogenous or/and endogenous agents and many mild effect inherited susceptibility mutations. Some of them are known, but their functional roles still requireinvestigation. Age is a recognized risk factor; children with disease onset after the age of ten have worse prognosis, presumably also triggered by inherited factors. Materials and Methods: The MDR1 gene polymorphisms rs1045642, rs2032582 and MTHFR gene polymorphisms rs1801131 and rs1801133 were genotyped in 68 ALL patients in remission and 102 age and gender matched controls; parental DNA samples were also available for 42 probands. Results: No case control association was found between analyzed polymorphisms and a risk of childhood ALL development. Linkage disequilibrium was not observed in a family-based association study either. Only marginal association was observed between genetic marker rs2032582A and later disease onset (p=0.04). Conclusions: Our data suggest that late age of ALL onset could be triggered by mild effect common alleles.

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Methylenetetrahydrofolate reductase (MTHFR) C677T and thymidylate synthase promoter (TSER) polymorphisms in Indonesian children with and without leukemia

Cited by 41 publications

References 25 publications

Thymidylate synthase enhancer region polymorphism not related to susceptibility to acute lymphoblastic leukemia in the Kashmir population

Thymidylate synthase enhancer region polymorphism not related to susceptibility to acute lymphoblastic leukemia in the Kashmir population

Candidate gene association studies and risk of childhood acute lymphoblastic leukemia: a systematic review and meta-analysis

Lack of Association between Polymorphisms in Genes MTHFR and MDR1 with Risk of Childhood Acute Lymphoblastic Leukemia

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