Gilliland F D
Department of Internal Medicine and Epidemiology, University of New Mexico School of Medicine, Albuquerque 87131, USA.
Environ Health Perspect. 1997 Jun;105 Suppl 4(Suppl 4):897-900. doi: 10.1289/ehp.97105s4897.
Cancer incidence varies markedly by ethnicity and geographic location. Ethnic variation in cancer occurrence has traditionally been ascribed to differences in social, cultural, economic, and physical environments. However, this interpretation of the epidemiologic evidence may need to be revised as a result of new biological evidence and theories of carcinogenesis. Carcinogenesis is now recognized to be a multistep process during which mutations or heritable changes in expression occur in genes involved in cellular growth control and genome stability. Inherited cancer susceptibility may be a stronger determinant of ethnic differences in cancer incidence than is currently appreciated. To examine the potential role of inherited susceptibility, the theoretical contribution of inherited susceptibility to ethnic differences in rates in considered using a simple probability model. Germline mutations in tumor suppressor genes BRCA1 and p53 are used to illustrate the magnitude of the ethnic differences for breast cancer that might arise from differences in inherited susceptibility. Our simple model suggests that ethnic differences in cancer occurrence can result from differences in genetic susceptibility. However, the magnitude of ethnic relative risk is likely to more strongly reflect differences in the distribution of susceptibility genotypes between groups than the magnitude of the disease risk associated with the genotypes. For many scenarios, the ethnic relative risk arising from differences in susceptibility may be bounded by the ratio of the proportion of susceptible individuals in each group.
癌症发病率在不同种族和地理位置之间存在显著差异。传统上，癌症发生的种族差异归因于社会、文化、经济和自然环境的不同。然而，鉴于新的生物学证据和致癌理论，这种对流行病学证据的解释可能需要修正。目前认为，致癌作用是一个多步骤过程，在此过程中，参与细胞生长控制和基因组稳定性的基因会发生突变或表达的可遗传变化。遗传性癌症易感性可能是癌症发病率种族差异的一个比目前所认识到的更强的决定因素。为了研究遗传性易感性的潜在作用，我们使用一个简单的概率模型来考量遗传性易感性对发病率种族差异的理论贡献。以肿瘤抑制基因BRCA1和p53的种系突变为例，来说明遗传性易感性差异可能导致的乳腺癌种族差异程度。我们的简单模型表明，癌症发生的种族差异可能源于遗传易感性的差异。然而，种族相对风险的大小可能更强烈地反映出不同群体之间易感性基因型分布的差异，而不是与这些基因型相关的疾病风险大小。在许多情况下，由易感性差异引起的种族相对风险可能受每组易感个体比例之比的限制。
