Data Mining for DNA Viruses with Breast Cancer and its Limitation

Breast cancer is very common worldwide, with 800,000 new cases diagnosed each year [Parkin et al,1999]. Among Taiwanese women, breast cancer is the second most common form of cancer (Cancer Registry Annual Report in Taiwan, 1998-2002) and the fourth leading cause of cancer-related death (Public Health Annual Report in Taiwan, 2002). The risk factors for development of breast cancer in Taiwan, a low incidence area, are similar to those in a moderate-to-high risk area [Yang et al,1997]. Although there are recognized factors that increase the risk of breast cancer, its causes are still unknown and thus there is no way of preventing it. This paper explores the possibility that viruses play a role in development of breast tumors. DNA viruses have been recognized as oncogenic in humans: Examples include EBV, which is associated with Burkitt lymphoma and nasopharyngeal carcinoma, HPV, which is associated with cervical cancer, and hepatitis B virus, which is associated with hepatocellular cancer. Viral DNA sequences have been found in breast tumors [Tsai et al,2005, ue et al,2003. Fina et al,2001. Labecque et al,1995. Horiuchi et al,1994. Kleer et al,2002], but it is not certain that the presence of the virus is related to development of breast tumors because similar sequences have been found in normal mammary tissue Tsai et al,2005. Pogo et al,1997]. Breast cancer is a multistep disease, and infection with a DNA virus could play a role in one or more of the steps in this pathogenic process [Labecque et al,1995]. In addition, it has been hypothesized that familial breast cancer and sporadic breast cancer are caused by different mechanisms. More recently, the differences between familial and sporadic breast cancers have be shown to be compatible with Knudson’s ‘two hit’ hypothesis [Knudson,1971. Richardson,1997],which suggests that at least two mutations are required before a cell becomes malignant. The reason thatwomen with familial predisposition to breast cancer are likely to develop it at a younger age and are also morelikely to develop bilateral disease is because they have inherited one of the two genetic defects (such as mutation of p53) that are required for breast cancer. These women require only one ‘hit’ to get breast cancer, whereas women with non-familial breast cancer start with no major mutations and thus need two‘hit’ Thisobservation is consistent with the hypothesis that breast cancer is caused in part by a virus. One of the ‘hit’required for development of breast cancer may be infection with a O pe n A cc es s D at ab as e w w w .in te ch w eb .o rg