Department of Oncology, Sahlgrenska University Hospital, SE-413 45 Göteborg, Sweden.
Acta Oncol. 2010 Apr;49(3):361-7. doi: 10.3109/02841860903521095.
In a previous cohort study, we showed that there was a significant variation in the frequency of ovarian cancer after having breast cancer in Sweden, with the highest risk occuring in the Western region. The present study aimed to evaluate whether the high prevalence of the founder mutation BRCA1 3171ins5 may explain the excess number of ovarian cancer.
Among more than 26 000 women with breast cancer in the Western Swedish Health Care Region, 159 cases were subsequently diagnosed with ovarian cancer, whereas the expected number was 96. Archived tissue material was analysed for six common Scandinavian BRCA1 and BRCA2 gene mutations.
The excess number of cases was 63 (95% CI 47-77), based on person-years at risk and national incidence rates of ovarian cancer. A BRCA1 gene mutation was detected in 33 cases corresponding to 52% of the excess number. The founder mutation, BRCA1 3171ins5, was detected in 44% of the excess number. The identified mutations decreased from 45% in women less than 50 years of age at follow-up to 14% at 60+ years at follow-up. There was no obvious decrease in mutation frequency by excess numbers with age. Age at follow-up and first-degree relatives with breast and/or ovarian cancer were the best predictors of a mutation in this material.
The founder mutation, BRCA1 3171ins5, explains the excess of ovarian cancer after breast cancer in the region. From the relative frequency of the studied mutations found at the cancer genetic counselling clinic, it is estimated that BRCA1 gene mutations are associated with about 80-85% of the excess cases. This means that a negative screening for these mutations in similar cases may have a predictive value and could strongly reduce the risk of ovarian cancer in relatives.
在之前的一项队列研究中，我们发现在瑞典，乳腺癌患者发生卵巢癌的频率存在显著差异，风险最高的是西部地区。本研究旨在评估高发性BRCA1 3171ins5 基因突变是否可以解释卵巢癌高发的原因。
在瑞典西部卫生保健区的 26000 多名乳腺癌患者中，有 159 例随后被诊断为卵巢癌，而预期的数字是 96 例。对存档的组织材料进行了 6 种常见斯堪的纳维亚 BRCA1 和 BRCA2 基因突变的分析。
根据风险人年和全国卵巢癌发病率，超额病例数为 63 例（95%CI 47-77）。在 33 例病例中检测到 BRCA1 基因突变，占超额病例数的 52%。检测到的突变基因包括 BRCA1 3171ins5 这种常见的突变基因，占超额病例数的 44%。在随访年龄小于 50 岁的女性中，识别出的突变率为 45%，而在随访年龄 60 岁及以上的女性中，这一比例降至 14%。随着年龄的增加，突变频率并没有明显下降。在本材料中，随访年龄和一级亲属中患有乳腺癌和/或卵巢癌是基因突变的最佳预测因子。
BRCA1 3171ins5 这种常见的突变基因解释了该地区乳腺癌患者发生卵巢癌的情况。根据在癌症遗传咨询诊所发现的研究突变的相对频率，估计 BRCA1 基因突变与大约 80-85%的超额病例有关。这意味着对类似病例进行这些突变的阴性筛查可能具有预测价值，并能强烈降低亲属发生卵巢癌的风险。
