Strong L C, Herson J, Haas C, Elder K, Chakraborty R, Weiss K M, Majumder P
J Natl Cancer Inst. 1984 Aug;73(2):303-11. doi: 10.1093/jnci/73.2.303.
The risk of other cancers in relatives of retinoblastoma (RTB) patients was determined by a survey of the mortality experience of siblings, parents, parental siblings, and grandparents of all U.S. or Canadian RTB patients referred to The University of Texas M.D. Anderson Hospital and Tumor Institute between 1944 and 1980. Expected mortality was ascertained by the application of age-, sex-, race-, and calendar year-specific U.S. mortality rates to the observed person-years. Among 607 relatives of 33 unilateral-sporadic RTB probands, no excess in cancer deaths was observed (observed/expected = 18/22). Among 733 relatives of 47 bilateral-familial RTB probands, a slight excess in cancer deaths was observed (41/31). A significant excess in cancer deaths was occurred in relatives under age 55 years (18/9) and in fathers (7/1) of the bilateral RTB probands. To determine whether the cancer excess was related to some unique allele associated with second tumors in RTB survivors, the cancer mortality of 203 relatives of the 14 RTB patients with second tumors was examined, and no excess was observed (11/11). To determine whether the excess might be attributable to an unexpressed RTB gene or precursor, the mortality experience was examined in 6 kindreds in which parents, unaffected by RTB, had more than 1 child with RTB. Among these 72 relatives a significant excess in cancer deaths was observed (8/2). The findings demonstrate a modest overall cancer excess in relatives of hereditary RTB patients and suggest it may be attributable to an unexpressed RTB gene or precursor in a small number of kindreds. Mechanisms for an apparent "precursor" might involve a delayed mutation, genetic mosaicism, or a submicroscopic balanced chromosomal translocation.
通过对1944年至1980年间转诊至德克萨斯大学MD安德森医院和肿瘤研究所的所有美国或加拿大视网膜母细胞瘤（RTB）患者的兄弟姐妹、父母、父母的兄弟姐妹及祖父母的死亡经历进行调查，确定了RTB患者亲属患其他癌症的风险。预期死亡率通过将美国特定年龄、性别、种族和日历年份的死亡率应用于观察到的人年数来确定。在33名单侧散发型RTB先证者的607名亲属中，未观察到癌症死亡人数过多（观察到的/预期的 = 18/22）。在47名双侧家族型RTB先证者的733名亲属中，观察到癌症死亡人数略有过多（41/31）。双侧RTB先证者55岁以下的亲属（18/9）和父亲（7/1）的癌症死亡人数显著过多。为了确定癌症过多是否与RTB幸存者中与第二种肿瘤相关的某些独特等位基因有关，对14名患有第二种肿瘤的RTB患者的203名亲属的癌症死亡率进行了检查，未观察到过多情况（11/11）。为了确定过多情况是否可能归因于未表达的RTB基因或前体，对6个家系的死亡经历进行了检查，在这些家系中，未受RTB影响的父母有不止一个孩子患RTB。在这72名亲属中，观察到癌症死亡人数显著过多（8/2）。这些发现表明，遗传性RTB患者的亲属总体上癌症略有过多，并表明这可能归因于少数家系中未表达的RTB基因或前体。明显“前体”的机制可能涉及延迟突变、遗传镶嵌现象或亚显微平衡染色体易位。
