Tutera A M, Sellers T A, Potter J D, Drinkard C R, Wiesner G L, Folsom A R
Division of Epidemiology, School of Public Health, University of Minnesota, Minneapolis 55454-1015, USA.
Genet Epidemiol. 1996;13(2):207-21. doi: 10.1002/(SICI)1098-2272(1996)13:2<207::AID-GEPI6>3.0.CO;2-4.
There are recent data to suggest that risk factors for breast cancer may differ according to whether the tumor expresses detectable levels of the estrogen receptor (ER) and progesterone receptor (PR). While a family history of breast cancer is one of the most consistent predictors of the disease, we recently reported a modest inverse association with ER+PR- tumors. However, the definition of a family history of cancer did not consider second-degree relatives or cancer sites that may be etiologically related. The current report presents additional data analysis from the Iowa Women's Health Study, a prospective population-based cohort study conducted among 41,837 postmenopausal women. At baseline in 1986, respondents provided information on family history of cancers of the breast, ovaries, or uterus/endometrium in their mothers, sisters, daughters, maternal and paternal grandmothers, and maternal and paternal aunts. Data on family history of prostate cancer in fathers and brothers and age at onset of breast cancer in mothers and sisters were collected in 1992. Cohort members were followed for cancer incidence through the statewide tumor registry. After 7 years and more than 235,000 person-years of follow-up, 939 incident cases of breast cancer were identified. Information was obtained from the tumor registry on ER (+/-) and PR (+/-) status for 610 cases (65.0%). A family history of breast cancer in first-degree relatives was associated with increased risk (relative risk [PR] = 1.4; 95% confidence interval [CI]: 1.1-1.6) for all receptor-defined subtypes of breast cancer except ER+PR- tumors (RR = 0.7; 95% CI: 0.3-1.4). These results were unchanged when data on second-degree relatives were included. When the onset of breast cancer in relatives occurred at or before the age of 45 years, increased risks were evident only for ER-PR+ and ER-PR- tumors (RR = 2.3 and 3.3, respectively). Conversely, when relatives were affected with breast cancer after the age of 45 years, increased risks were most apparent for ER+PR+ and ER-PR+ tumors (RR = 1.3 and 3.2, respectively). A family history of prostate cancer in first-degree relatives was associated with a 1.2-fold increased risk of breast cancer (95% CI: 0.98-1.50), largely a reflection of the association with ER-PR- tumors (RR = 1.5; 95% CI: 0.8-3.0). The small numbers of cases in some categories and the corresponding wide CIs preclude definitive conclusions, but these data are at least suggestive that joint stratification of breast tumors on ER and PR status may be useful in partitioning breast cancer families into more homogeneous subsets.
近期有数据表明，乳腺癌的风险因素可能因肿瘤是否表达可检测水平的雌激素受体（ER）和孕激素受体（PR）而有所不同。虽然乳腺癌家族史是该疾病最一致的预测因素之一，但我们最近报告了ER + PR - 肿瘤与之存在适度的负相关。然而，癌症家族史的定义并未考虑二级亲属或可能在病因上相关的癌症部位。本报告展示了爱荷华州女性健康研究的更多数据分析，这是一项针对41,837名绝经后女性进行的基于人群的前瞻性队列研究。在1986年基线时，受访者提供了关于其母亲、姐妹、女儿、外祖母和祖母以及姨妈患乳腺癌、卵巢癌或子宫/子宫内膜癌家族史的信息。1992年收集了父亲和兄弟患前列腺癌家族史以及母亲和姐妹患乳腺癌发病年龄的数据。通过全州肿瘤登记处对队列成员的癌症发病率进行随访。经过7年及超过235,000人年的随访，共确定了939例乳腺癌发病病例。从肿瘤登记处获取了610例病例（65.0%）的ER（+/-）和PR（+/-）状态信息。除ER + PR - 肿瘤外（RR = 0.7；95%置信区间[CI]：0.3 - 1.4），一级亲属患乳腺癌家族史与所有受体定义的乳腺癌亚型风险增加相关（相对风险[RR] = 1.4；95%置信区间[CI]：1.1 - 1.6）。纳入二级亲属数据后，这些结果未变。当亲属患乳腺癌发病年龄在45岁及之前时，仅ER - PR +和ER - PR - 肿瘤风险增加明显（RR分别为2.3和3.3）。相反，当亲属患乳腺癌发病年龄在45岁之后时，ER + PR +和ER - PR +肿瘤风险增加最为明显（RR分别为1.3和3.2）。一级亲属患前列腺癌家族史与乳腺癌风险增加1.2倍相关（95%置信区间[CI]：0.98 - 1.50），这在很大程度上反映了与ER - PR - 肿瘤的关联（RR = 1.5；95%置信区间[CI]：0.8 - 3.0）。某些类别中的病例数较少以及相应较宽的置信区间使得无法得出确定性结论，但这些数据至少表明，根据ER和PR状态对乳腺肿瘤进行联合分层可能有助于将乳腺癌家族划分为更同质的亚组。
