Olsen J H, Seersholm N, Boice J D, Krüger Kjaer S, Fraumeni J F
Institute of Cancer Epidemiology, Danish Cancer Society, Copenhagen.
Br J Cancer. 1999 Feb;79(3-4):673-9. doi: 10.1038/sj.bjc.6690106.
Inherited susceptibility to breast cancer is associated with an early onset and bilateral disease. The extent of familial risks has not, however, been fully assessed in population-based incidence studies. The purpose of the study was to quantify the risks for cancers of the breast, ovary and other sites of close relatives of women in whom breast cancer was diagnosed at an early age. Records collected between 1943 and 1990 at the Danish Cancer Registry were searched, and 2860 women were found in whom breast cancer was diagnosed before age 40. Population registers and parish records were used to identify 14 973 parents, siblings and offspring of these women. Cancer occurrence through to 31 December 1993 was determined within the Cancer Registry's files and compared with national incidence rates. Women with early-onset breast cancer were at a nearly fourfold increased risk of developing a new cancer later in life (268 observed vs. 68.9 expected). The excess risk was most evident for second cancer of the breast (181 vs. 24.5) and for ovarian cancer (20 vs. 3.3). For mothers and sisters, risks for cancers of the breast and ovary were significantly increased by two- to threefold. Bilateral breast cancer and breast-ovarian cancer were very strong predictors of familial risks, with one in four female relatives predicted to develop breast and/or ovarian cancer by age 75. Mothers had a slightly increased risk of colon cancer, but not endometrial cancer. The risk for breast cancer was also increased among fathers (standardized incidence ratio 2.5; 95% CI 0.5-7.4) and especially brothers (29; 7.7-74), although based on small numbers. The risk for prostatic cancer was unremarkable. In this large population-based survey, the first-degree relatives of women who developed breast cancer before age 40 were prone to ovarian cancer as well as male and female breast cancer, but not other tumours that may share susceptibility genes with breast cancer.
遗传性乳腺癌易感性与发病早及双侧病变相关。然而，基于人群的发病率研究尚未全面评估家族性风险程度。本研究的目的是量化早年被诊断为乳腺癌的女性的近亲患乳腺癌、卵巢癌及其他部位癌症的风险。检索了丹麦癌症登记处1943年至1990年间收集的记录，发现2860名女性在40岁之前被诊断为乳腺癌。利用人口登记册和教区记录来确定这些女性的14973名父母、兄弟姐妹及子女。通过癌症登记处的档案确定截至1993年12月31日的癌症发病情况，并与全国发病率进行比较。早年患乳腺癌的女性在晚年患新发癌症的风险增加近四倍（观察到268例，预期68.9例）。额外风险在乳腺癌的二次发病（181例 vs. 24.5例）和卵巢癌（20例 vs. 3.3例）中最为明显。对于母亲和姐妹，患乳腺癌和卵巢癌的风险显著增加两到三倍。双侧乳腺癌和乳腺 - 卵巢癌是家族性风险的很强预测指标，四分之一的女性亲属预计到75岁时会患乳腺癌和/或卵巢癌。母亲患结肠癌的风险略有增加，但子宫内膜癌风险未增加。父亲（标准化发病率比2.5；95%可信区间0.5 - 7.4）尤其是兄弟（29；7.7 - 74）患乳腺癌的风险也增加，尽管病例数较少。前列腺癌风险不显著。在这项基于人群的大型调查中，40岁之前患乳腺癌的女性的一级亲属易患卵巢癌以及男性和女性乳腺癌，但不易患可能与乳腺癌共享易感基因的其他肿瘤。
