Some selected oxidative stress parameters were measured in 56 Fanconi anaemia (FA) patients (42 untransplanted and 14 transplanted), 54 FA heterozygotes (parents) and 173 controls. Untransplanted FA patients showed a highly significant increase in leukocyte 8-hydroxy-2'-deoxyguanosine (8-OHdG) (P = 0.00003) and a borderline increase (P = 0.076) in urinary levels of 8-OHdG versus child controls. These increases were more pronounced in female FA patients (P = 0.00005 for leukocyte 8-OHdG and P = 0.021 for urinary 8-OHdG). Female FA patients also displayed a highly significant excess of spontaneous chromosomal breaks versus male patients (P = 0.00026), in the same female:male ratio ( approximately 1.4) as detected for both leukocyte and urine 8-OHdG levels. Plasma methylglyoxal (MGlx) levels were increased in untransplanted FA patients versus child controls (P = 0.032). The increases in leukocyte and urinary 8-OHdG and in MGlx levels were detected in young FA patients (< or =15 years), whereas patients aged 16-29 years failed to display any differences versus controls in the same age group. A significant increase in oxidized:reduced glutathione (GSSG:GSH) ratio was observed (P = 0.046) in the FA patients aged < or =15 years, whereas those aged 16-29 years, both untransplanted and transplanted, displayed a decrease (P = 0.06) in the GSSG:GSH ratio versus the controls of the respective age groups. No significant changes were detected in plasma levels of vitamin C, vitamin E or uric acid. Transplanted FA patients showed lesser alterations in leukocyte 8-OHdG and in GSSG:GSH ratio versus untransplanted patients. The parents of FA patients displayed a significant increase in plasma MGlx levels (P = 0.0014) versus adult controls. The results suggest a gender- and age-related modulation of oxidative stress in FA patients. The observed increase in urinary 8-OHdG in untransplanted FA patients suggests a proficient removal of oxidized DNA bases.
BACKGROUND: Alterations in DNA methylation and histone modifications have been implicated in carcinogenesis. Although tumor-specific alterations in DNA methylation can be detected in the serum and plasma of cancer patients, no data are available on the presence of histone modifications in circulating blood. We investigated whether histone methylation, as a model of histone modifications, is detectable in plasma. Because methylation at histone 3 lysine 9 (H3K9) has been demonstrated to be enriched at sites of repetitive ALU elements, we addressed the specificity of histone-methylation detection and hypothesized that if monomethylated H3K9 (H3K9me1) is detectable in plasma, the concentrations in mononucleosomes and oligonucleosomes would be different. We also analyzed a single-copy gene, CDKN2A.
Background. MicroRNAs are a type of small noncoding RNA molecules that have been shown to control gene expression in eukaryotes. Aberrant expression and alteration of miRNAs may be responsible for human diseases including cancer. An miR16-1 (C > T) + 7 gene mutation has been previously found in familial chronic lymphocytic leukemia patients, one of which reported a family history of breast cancer. miR16-1 regulates the expression of bcl-2, which is important in retinoblastoma, and is located in a genomic region that is frequently lost in nasopharyngeal and hepatocellular carcinomas (HCCs). Therefore, miR16-1 may be potentially important in the etiology of several solid tumors. To understand the power of the miR16-1 (C > T) + 7 mutation as a prognostic and diagnostic risk factor, we investigated the mutation in patients with seven different types of cancer including 188 with breast, 102 with ovarian, and 22 nasopharyngeal carcinomas, 96 HCC, 872 chronic myeloid leukemia (CML), 39 chronic lymphocytic leukemia (CLL), and 46 retinoblastoma cases from three different ethnic groups and of hereditary and sporadic etiology. Methods. 5′Nuclease TaqMan SNP genotyping assay was used to detect the miR16-1 gene C > T substitution. Results. The miR16-1 (C > T) + 7 substitution was not detected in any of the groups studied. Conclusions. Considering the large scale of our study, the representation of different ethnicities and levels of hereditary risk, we conclude that the miR-16-1 (C > T) + 7 mutation is not a good diagnostic or prognostic indicator of risk for the cancers tested.
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