To the Editors: Pelucchi et al. found that folate deficiency increases prostate cancer risk (1). They attributed this to DNA hypomethylation and uracil misincorporation leading to chromosome breaks. However, mitochondrial DNA (mtDNA) should be considered as well. Like chromosomal DNA, mtDNA is vulnerable to breaks due to the uracil excision process (2).

Crott et al. found that folate reduced the level of 4.8 kb deletion in rat mtDNA (2). The 4.8 kb deletion is homologous to the common 4,977 bp deletion in human mtDNA. The common 4,977 bp deletion results in an increased generation of reactive oxygen species (3), which are tumorigenic (4).

Damage to mtDNA, as well as chromosomal DNA, should be considered when looking at the relationship between folate and cancer.

1

The authors of the original article were invited to respond but did not do so.

1
Pelucchi C, Galeone C, Talamini R, et al. Dietary folate and risk of prostate cancer in Italy.
Cancer Epidemiol Biomarkers Prev
2005
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14
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944
–8.
2
Crott JW, Choi SW, Branda RF, Mason JB. Accumulation of mitochondrial DNA deletions is age, tissue and folate-dependent in rats.
Mutat Res
2005
;
570
:
63
–70.
3
Lu CY, Lee HC, Fahn HJ, Wei YH. Oxidative damage elicited by imbalance of free radical scavenging enzymes is associated with large-scale mtDNA deletions in aging human skin.
Mutat Res
1999
;
423
:
11
–21.
4
Storz P. Reactive oxygen species in tumor progression.
Front Biosci
2005
;
10
:
1881
–96.