Cancer risk in hereditary nonpolyposis colorectal cancer syndrome: Later age of onset
Cancer risk in hereditary nonpolyposis colorectal cancer syndrome: Later age of onset
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DOI：
10.1053/j.gastro.2005.05.011
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发表时间：
2005-08-01
期刊：
影响因子：
29.4
通讯作者：
de la Chapelle, A
中科院分区：
文献类型：
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作者：
Hampel, H;Stephens, JA;de la Chapelle, A
背景和目标：错配修复基因的突变导致遗传性非息肉病性结直肠癌（HNPCC）综合征，并传递结直肠癌（CRC）和子宫内膜癌的高终生癌症风险。目前，HNPCC个体的癌症风险是基于临床确定的家庭数据。本研究的目的是使用来自地理上定义的区域的综合数据集重新检查HNPCC的异常率。研究方法：使用了通过传统高危标准和分子筛查确定的70个HNPCC家族的组合数据集，其中包括88名先证者和373名突变阳性家族成员。统计方法采用改良生存分析技术。结果如下：在突变阳性的亲属中（排除先证者），诊断CRC的中位年龄为61.2岁（置信区间[CI]，56.3-68.0岁）。CRC的终生风险男性为68.7%（CI，58.6%-78.9%），女性为52.2%（CI，37.6%-66.9%）。仅考虑先证者，诊断CRC的中位年龄为44.0岁（CI，41.0 - 46.3岁）。EC发病的中位年龄为62.0岁（CI，55.9岁，上限过高，无法计算），终生癌症风险为54%（CI，41.9%-66.1%）。结论：61岁时CRC的发病年龄明显晚于以前报道的（类似于44岁），这主要是由于考虑了所有基因阳性个体（受影响和未受影响的癌症）的更严格的分析方法。CRC和子宫内膜癌的终生癌症风险可能低于目前的假设。如果得到证实，这些数据表明需要改变咨询实践，并考虑HNPCC在老年人比以前。
Background & Aims: Mutations in the mismatch repair genes cause hereditary nonpolyposis colorectal cancer (HNPCC) syndrome and convey high lifetime cancer risks for colorectal (CRC) and endometrial cancer. Currently, cancer risks for individuals with HNPCC are based on data from clinically ascertained families. The purpose of this study was to re-examine the penetrance in HNPCC using a comprehensive dataset from a geographically defined region. Methods: A combined dataset of 70 HNPCC families ascertained by traditional high-risk criteria and by molecular screening comprising 88 probands and 373 mutation-positive family members was used. Statistical methods were modified survival analysis techniques. Results: In mutation-positive relatives (excluding probands), the median age at diagnosis of CRC was 61.2 years (confidence interval [CI], 56.3-68.0 y). The lifetime risk for CRC was 68.7% (CI, 58.6%-78.9%) for men and 52.2% (CI, 37.6%-66.9%) for women. Considering only probands, the median age at diagnosis of CRC was 44.0 years (CI, 41.0 - 46.3 y). Median age of onset of EC was 62.0 years (CI, 55.9 y to an upper limit too high to calculate) with a lifetime cancer risk of 54% (CI, 41.9%-66.1%). Conclusions: A markedly later age of onset for CRC at 61 y than previously reported (similar to 44 y) is suggested, resulting mainly from a more rigorous method of analysis in which all gene-positive individuals (both affected and unaffected with cancer) are considered. Lifetime cancer risks may be lower for CRC and endometrial cancer than presently assumed. If confirmed, these data suggest a need to alter counseling practices, and to consider HNPCC in older individuals than before.