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Is there a folate-related gene-environment interaction in the etiology of childhood acute lymphoblastic leukemia?
Elizabeth Milne1, Nicholas H de Klerk, Frank van Bockxmeer
1Telethon Institute for Child Health Research, Centre for Child Health Research, The University of Western Australia, WA, Australia. lizm@ichr.uwa.edu.au
Insights
Maternal folate supplementation and child
Area of Science:
- Pediatric Oncology
- Nutritional Epidemiology
- Genetic Epidemiology
Background:
- Acute lymphoblastic leukemia (ALL) is the most frequent childhood cancer.
- Maternal folate intake and child's methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms are potential factors in ALL etiology.
- Previous research suggests a protective effect of maternal folate supplementation and certain MTHFR genotypes against childhood ALL.
Purpose of the Study:
- To investigate the interaction between maternal folate supplementation during pregnancy and the child's MTHFR genotype (C677T and A1298C) in relation to childhood ALL risk.
- To analyze data from a previous study on childhood ALL cases.
Main Methods:
- Case-only analysis was employed using bone marrow DNA from 82 childhood ALL cases.
- Genotyping for MTHFR C677T and A1298C polymorphisms was performed.
- Case-only odds ratios (COR) were calculated to assess the association between MTHFR genotype, folate supplementation, and ALL.
Main Results:
- No significant departure from a multiplicative model was observed, indicating no statistically significant interaction between maternal folate supplementation and the child's MTHFR genotype (C677T or A1298C) in relation to ALL risk.
- Adjustments for sex, age, or the other MTHFR locus genotype did not alter the findings.
Conclusions:
- This study did not find evidence of an interaction between maternal folate supplementation and child's MTHFR genotype in childhood ALL.
- Contradictory findings in gene-environment interaction studies may stem from differing definitions of folate exposure.
- Further research is warranted to elucidate the complex interplay of folate intake and genetic factors in ALL and other cancers.
Abstract:
Acute lymphoblastic leukaemia (ALL) is the commonest childhood cancer in developed countries. Little is known about its causes, although its early age at diagnosis has focused interest on maternal and perinatal factors. We have previously observed a protective effect of maternal folate supplementation during pregnancy against ALL, and a number of studies have reported protective effects of some common polymorphisms of the methylenetetrahydrofolate reductase (MTHFR) gene. One study has suggested that the effect of MTHFR polymorphisms on risk of ALL may depend on folate status. This study aimed to look for evidence of an interaction between maternal folate supplementation and child's genotype among the cases from our previous study. Bone marrow specimens from 82 of 83 case children were available. DNA was extracted and genotyped for MTHFR C677T and A1298C using standard techniques. We used a case-only analysis to estimate the case-only odds ratio (COR) for MTHFR genotype and folate supplementation in association with ALL. None of the CORs indicated a significant departure from a multiplicative model. Adjustment for sex, age or genotype at the other locus had little effect on the results. Other studies of this gene and environment interaction in ALL and other cancers have produced contradictory results, perhaps because of varying definitions of folate exposure. Further research into the interaction of folate intake and genotype in causing ALL and other cancers is needed. We are specifically studying it in an Australian national case-control study of genetic and environmental causes of ALL.
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