Folate Pathway Gene Polymorphisms and Risk of Childhood Brain Tumors: Results from an Australian Case–Control Study

Greenop, Kathryn R.; Scott, Rodney J.; Attia, John; Bower, Carol; Klerk, Nicholas de; Norris, Murray D.; Haber, Michelle; Jamieson, Sarra E.; Bockxmeer, Frank M. van; Gottardo, Nicholas G.; Ashton, Lesley J.; Armstrong, Bruce K.; Milne, Elizabeth

doi:10.1158/1055-9965.epi-14-1248

Cited by 5 publications

(2 citation statements)

References 28 publications

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“…Overall, 72 publications including 85 studies of 32,272 cases and 37,427 controls were included in the final meta-analysis. Of the 85 studies, 20 studies focused on colorectal cancer 11 , 14 , 17 , 18 , 20 , 31 , 37 , 40 , 44 , 49 - 52 , 55 , 66 , 70 , 71 , ten on breast cancer 19 , 22 , 36 , 38 , 44 , 47 , 62 , 64 , 76 , 82 , nine on acute lymphoblastic leukemia (ALL) 13 , 24 , 29 , 41 , 42 , 53 , 56 , 59 , 60 , eight on gastric cancer 12 , 27 , 31 , 46 , 65 , 67 , 74 , 79 , five on non-Hodgkin lymphoma (NHL) 13 , 30 , 32 , 58 , 78 , four each on cervical cancer 48 , 54 , 68 , 72 and liver cancer 33 , 74 , 75 , 81 , three each on prostate cancer 35 , 45 , 69 , head and neck cancer 16 , 25 , 61 and brain cancer 28 , 73 , 77 , and “other cancers” with no more than two studies. There were 37 studies on Asians, 32 studi...…”

Section: Resultsmentioning

confidence: 99%

Association of MTRR A66G polymorphism with cancer susceptibility: Evidence from 85 studies

Wang

et al. 2017

J. Cancer

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Methionine synthase reductase (MTRR) is a key regulatory enzyme involved in the folate metabolic pathway. Previous studies investigating the association of MTRR A66G polymorphism with cancer susceptibility reported inconclusive results. We performed the current meta-analysis to obtain a more precise estimation of the possible association. Published literatures were identified from PubMed, Embase and CBM databases up to October 2016. The strength of the association between the MTRR A66G polymorphism and cancer susceptibility was assessed using odds ratios (ORs) and the corresponding 95% confidence intervals (CIs). Eighty five published studies with 32,272 cases and 37,427 controls were included in this meta-analysis. Pooled results indicated that the MTRR A66G polymorphism was associated with an increased overall cancer risk (homozygous model: OR = 1.08, 95% CI = 1.02-1.15, P = 0.009; recessive model: OR = 1.06, 95% CI = 1.00-1.12, P < 0.001 and allele comparison: OR = 1.03, 95% CI = 1.00-1.06, P < 0.001). Stratification analysis further indicated significant associations in head and neck cancer, Caucasians, Africans, and high quality studies. However, to avoid the “false-positive report”, the significant findings were assessed by the false-positive report probability (FPRP) test. Interestingly, the results of FPRP test revealed that the increased risk for MTRR A66G polymorphism among Africans need further validation due to the high probabilities of false-positive results. This meta-analysis suggests that the MTRR A66G polymorphism is associated with significantly increased cancer risk, a finding that needs to be confirmed in single large studies.

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Section: Resultsmentioning

confidence: 99%

Association of MTRR A66G polymorphism with cancer susceptibility: Evidence from 85 studies

Wang

et al. 2017

J. Cancer

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“…Several studies and meta-analyses on the role of folate pathway gene variants in pediatric and adult acute leukemia focused on risk disease, treatment efficacy, and survival disclosing interesting pharmacogenetics considerations [36,37,38]. Less investigated in pediatric cancers is instead the mother-child dyad or parent-child triad approach [39,40,41,42]. The present study was conducted within the frame of the GEMCDS study aimed to recognize any genetic and epigenetic factor with prognostic role and effect on any aspect of childhood ALL.…”

Section: Discussionmentioning

confidence: 99%

Maternal Haplotypes in DHFR Promoter and MTHFR Gene in Tuning Childhood Acute Lymphoblastic Leukemia Onset-Latency: Genetic/Epigenetic Mother/Child Dyad Study (GEMCDS)

Tisato

Muggeo²,

Lupiano

et al. 2019

Genes

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Childhood acute lymphoblastic leukemia (ALL) peaks around age 2–4, and in utero genetic epigenetic mother-fetus crosstalk might tune ALL onset during childhood life. Folate genes variably interact with vitamin status on ALL risk and prognosis. We investigated DHFR and MTHFR gene variants in 235 ALL children and their mothers to disclose their role in determining ALL onset age and survival. Pyrosequence of DHFR 19bp ins/del (rs70991108; W/D), MTHFR C677T (rs1801133; C>T), and MTHFR A1298C (rs1801131; A>C) was assessed in children and in 72% of mothers for dyad-analysis comparison. DHFR DD-children had delayed ALL onset compared to WW-children (7.5 ± 4.8 vs. 5.2 ± 3.7 years; P = 0.002) as well as MTHFR 1298 CC-children compared to AA-children (8.03 ± 4.8 vs. 5.78 ± 4.1 years; P = 0.006), and according to the strong linkage disequilibrium between MTHFR 677 T-allele and 1298C-allele, MTHFR TT-children showed early mean age of onset though not significant. Offspring of MTHFR 677 TT-mothers had earlier ALL onset compared to offspring of 677 CC-mothers (5.4 ± 3.3 vs. 7 ± 5.3 years; P = 0.017). DHFR/MTHFR 677 polymorphism combination influenced onset age by comparing DD/CC vs. WW/TT children (8.1 ± 5.7 vs. 4.7 ± 2.1 years; P = 0.017). Moreover, mother-child genotype combination gave 5.5-years delayed onset age in favor of DD-offspring of 677 CC-mothers vs. WW-offspring of 677 TT-mothers, and it was further confirmed including any D-carrier children and any 677 T-carrier mothers (P = 0.00052). Correction for multiple comparisons maintained statistical significance for DHFR ins/del and MTHFR A1298C polymorphisms. Unexpectedly, among the very-early onset group (<2.89 years; 25th), DD-genotype inversely clustered in children and mothers (4.8% vs. 23.8% respectively), and accordingly ALL offspring of homozygous DD-mothers had increased risk to have early-onset (adjusted OR (odds ratio) = 3.08; 1.1–8.6; P = 0.03). The opposite effect DHFR promoter variant has in tuning ALL onset-time depending on who is the carrier (i.e., mother or child) might suggest a parent-origin-effect of the D-allele or a two-faced epigenetic role driven by unbalanced folate isoform availability during the in-utero leukemogenesis responsible for the wide postnatal childhood ALL latency.

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Folates: Chemistry, analysis, occurrence, biofortification and bioavailability

Saini

Nile

Keum

2016

Food Research International

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Folate Pathway Gene Polymorphisms and Risk of Childhood Brain Tumors: Results from an Australian Case–Control Study

Cited by 5 publications

References 28 publications

Association of MTRR A66G polymorphism with cancer susceptibility: Evidence from 85 studies

Association of MTRR A66G polymorphism with cancer susceptibility: Evidence from 85 studies

Maternal Haplotypes in DHFR Promoter and MTHFR Gene in Tuning Childhood Acute Lymphoblastic Leukemia Onset-Latency: Genetic/Epigenetic Mother/Child Dyad Study (GEMCDS)

Folates: Chemistry, analysis, occurrence, biofortification and bioavailability

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