Abstract 913: 5,10-Methylenetetrahydrofolate reductase C677T allele frequency and childhood leukemia incidence in predominantly European ancestry countries

Abstract

Abstract 5,10-Methylentetrahydrofolate reductase (MTHFR) single nucleotide polymorphisms (SNPs) have been intensely studied as cancer susceptibility alleles. For childhood leukemia, data have indicated that the most commonly studied MTHFR SNP, C677T, is associated with a slightly reduced risk of acute lymphoblastic leukemia (ALL). Both childhood leukemia incidence and MTHFR allele frequencies show variation worldwide. Our objective was to conduct an ecologic study to determine whether the MTHFR C677T allele frequency and childhood leukemia incidence are associated. We used cancer incidence data collected by the International Agency for Cancer Research from 22 registries that captured 19,025 leukemia cases diagnosed between the ages of 0 and 14 years from the United States, Canada, Australia, and 18 European countries; data were restricted to registries with majority European ancestry populations in order to minimize confounding by ancestry. MTHFR allele frequencies were gathered from the literature to match as closely as possible the registry populations. We modeled the association between childhood leukemia incidence and MTHFR C677T allele frequency using Poisson regression to calculate rate ratios (RRs) and 95% confidence intervals (CIs). Estimates of the minor C677T allele frequency ranged from 24% in Finland to 44% in Italy. There was a weak inverse correlation between leukemia incidence and MTHFR C677T allele frequency (r=0.19), that was stronger for ALL (r=0.30). Acute nonlymphoblastic leukemia (ANLL) incidence was positively correlated with MTHFR C677T allele frequency (r=0.36). Poisson regression results from linear models showed that the incidence of childhood leukemia decreased by 5% (95% CI 3%-6%) for every 5% increase in the C677T allele frequency. A similar pattern was observed for ALL with a RR of 0.93 (95% CI=0.92-0.95) but not acute non-lymphoblastic leukemia (ANLL) (RR=1.04, 95% CI=1.00-1.07). The significant inverse associations between the C677T allele frequency and leukemia and ALL incidence were specific to incidence rates for children diagnosed <10 years. These results are consistent with the results of case-control studies of the association between childhood leukemia and MTHFR allele frequency suggesting a modest risk reduction in association with the C677T allele. The strengths and limitations of ecological vs. case control study designs will be discussed in the context of these results to provide insight into the causal relationship between the MTHFR minor allele frequency and childhood leukemia risk. This research was supported by NIH grant T32 CA099936. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 913.