to be deficient and DNA damages can accumulate. Increased DNA damage can cause increased errors during DNA synthesis, leading to mutations that give rise to cancer. Induced by heavy metals The heavy metals cadmium, arsenic and nickel are all carcinogenic when present above certain levels. Cadmium is known to be carcinogenic, possibly due to reduction of DNA repair. Lei et al. evaluated five DNA repair genes in rats after exposure of the rats to low levels of cadmium. They found that cadmium caused repression of three of the DNA repair genes: XRCC1 needed for base excision repair, OGG1 needed for base excision repair, and ERCC1 needed for nucleotide excision repair. Repression of these genes was not due to methylation of their promoters. Arsenic carcinogenicity was reviewed by Bhattacharjee et al. They summarized the role of arsenic and its metabolites in generating oxidative stress, resulting in DNA damage. In addition to causing DNA damage, arsenic also causes repression of several DNA repair enzymes in both the base excision repair pathway and the nucleotide excision repair pathway. Bhattacharjee et al. further reviewed the role of arsenic in causing telomere dysfunction, mitotic arrest, defective apoptosis, as well as altered promoter methylation and miRNA expression. Each of these alterations could contribute to arsenic-induced carcinogenesis. Nickel compounds are carcinogenic and occupational exposure to nickel is associated with an increased risk of lung and nasal cancers. Nickel compounds exhibit weak mutagenic activity, but they considerably alter the transcriptional landscape of the DNA of exposed individuals. Arita et al. examined the peripheral blood mononuclear cells of eight nickel-refinery workers and ten non-exposed workers. They found 2756 differentially expressed genes with 770 up-regulated genes and 1986 down-regulated genes. DNA repair genes were significantly over-represented among the differentially expressed genes, with 29 DNA repair genes repressed in the nickel-refinery workers and two over-expressed. The alterations in gene expression appear to be due to epigenetic alterations of histones, methylations of gene promoters, and hypermethylation of at least microRNA miR-152. Clinical signs Malignant transformation of cells in a benign tumor may be detected by pathologic examination of tissues. Often the clinical signs and symptoms are suggestive of a malignant tumor. The physician, during the medical history examination, can find that there have been changes in size or patient sensation and, upon direct examination, that there has been a change in the lesion itself. Risk assessments can be done and are known