Genetic Susceptibility of Breast Cancer in Korea -Molecular Epidemiological Approaches-

Abstract

Breast cancer is the most prevalent cancer among women in Western countries and its prevalence is also increasing in Asia. (1,2) In 1994, the incidence rate of female breast cancer in Korea, adjusted for the world population, was 10.9 per 100,000, which was far lower than those of Western countries and even lower than those of other Asian countries. The major risk factors relating to breast cancer can be traced to reproductive events influencing lifetime levels of hormones.(3,4) A large proportion of breast cancer cases cannot, however, be explained by the above risk factors. The identification of susceptibility factors predisposing an individual to breast cancer, if exposed to particular environmental agents, could possibly give further insight into the etiology of this malignancy. Inherited differences in the capacity to metabolize environmental carcinogens have recently been suggested to modify individual susceptibilities to breast cancer. Therefore, the identification of new breast cancer susceptibility genes might yield new insight into breast tumorigenesis, and could provide targets for future therapeutic developments. In this respect the most interesting candidate genes include those mediating a range of functions, such as carcinogen metabolism, DNA repair, steroid hormone metabolism, signal transduction, and cell cycle control. Although the relative risks of these low penetrance susceptibility genes, to the development of breast cancer, are generally lower than those from high penetrance susceptibility genes (e.g., BRCA1, BRCA2, etc.), the attributable risk of low penetrance genes are much higher than those of the high penetrance genes, since the frequency of their variant alleles are higher in the general population. Thus, higher public health significance lays with these low penetrance genes, With their use it may be possible to obtain greater mechanistic insights into human breast carcinogenesis as well as targeted preventive approaches to the individuals with ‘at risk’ genotypes (Table 1). We have conducted a hospital based case-control study in South Korea to further evaluate the potential modifying role of the genetic polymorphisms of selected genes involved in the metabolism of carcinogens, estrogen metabolism, signal transduction, and DNA repair, also taking into account the potential interaction between these and known risk factors of breast cancer (Table 2). The results from selected genes will be presented in this mini-review.