Cancer risks for mismatch repair gene mutation carriers: A population-based early onset case-family study
Cancer risks for mismatch repair gene mutation carriers: A population-based early onset case-family study
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DOI：
10.1016/j.cgh.2006.01.002
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发表时间：
2006-04-01
影响因子：
12.6
通讯作者：
Southey, MC
中科院分区：
文献类型：
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作者：
Jenkins, MA;Baglietto, L;Southey, MC
背景和目标：错配修复基因突变携带者的癌症风险几乎完全来自于由于其强大的癌症家族史而确定的家族。由于分析问题，这些可能被高估，并且不可推广。我们估计了在基于人群的早发性结直肠癌病例（先证者）家族史中发现的突变的平均癌症风险。研究方法：数据为45岁之前诊断为结直肠癌的17名错配修复基因突变携带者先证者（8名hMLH 1，4名hMSH 2，4名hMSH 6，1名hPMS 2）及其一级和二级亲属的癌症病史和突变状态（携带者，非携带者或未知）。我们采用改良的分离分析理论，通过先证者是早发性突变携带者来确定家系。结果：11名携带者先证者（64%）来自符合遗传性非息肉病性结直肠癌Amsterdam II标准的家族。到70岁，男性和女性患结直肠癌的累积风险（95%置信区间）分别为45%（29%-62%）和38%（19%-51%）。任何遗传性非息肉病性结直肠癌相关癌症的相应风险分别为67%（47%-84%）和72%（48%-85%）。与普通人群相比，男性结直肠癌的发病率在50岁之前约高出180倍，但在50岁之后大致相同。对于女性，50岁之前的发病率约高出100倍，50岁之后的发病率高出7倍。结论：对于导致早发性结直肠癌的错配修复基因突变的携带者，结直肠癌在50岁之前迅速增加，并且在年龄较大时发病率降低到一般人群水平。
Background&Aims: Cancer risks for mismatch repair gene mutation carriers have been derived almost exclusively using families ascertained owing to their strong cancer family history. These may be overestimates, due to analytic problems, and not generalizable. We estimated average cancer risks for mutations identified in population-based early onset colorectal cancer cases (probands) unselected for family history. Methods: Data were cancer histories and mutation status (carrier, noncarrier, or unknown) of 17 mismatch repair gene mutation carrier probands with colorectal cancer diagnosed before age 45 (8 hMLH1, 4 hMSH2, 4 hMSH6, 1 hPMS2) and their first- and second-degree relatives. We used modified segregation analysis theory, adjusting for the family being ascertained through the proband being an early onset mutation carrier. Results: Eleven carrier probands (64%) were from families meeting the Amsterdam II criteria for hereditary nonpolyposis colorectal cancer. The cumulative risk for colorectal cancer (95% confidence interval) to age 70 was 45% (29%-62%) for men and 38% (19%-51%) for women. Corresponding risks were 67% (47%-84%) and 72% (48%-85%) for any hereditary nonpolyposis colorectal cancer-related cancer. Compared with the general population, colorectal cancer incidence for men was approximately 180-fold higher before age 50, but about the same after age 50. For women, incidence was approximately 100-fold higher before age 50 and 7-fold higher thereafter. Conclusions: For carriers of the mutations in the mismatch repair genes that cause early onset colorectal cancer, colorectal cancer increases rapidly until age 50, and the incidence decreases to general population levels at older ages.