Association of family history with cancer recurrence and survival among patients with stage III colon cancer
Association of family history with cancer recurrence and survival among patients with stage III colon cancer
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DOI：
10.1001/jama.299.21.2515
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发表时间：
2008-06-04
影响因子：
120.7
通讯作者：
Fuchs, Charles S.
中科院分区：
文献类型：
--
作者：
Chan, Jennifer A.;Meyerhardt, Jeffrey A.;Fuchs, Charles S.
背景：一级亲属的结直肠癌家族史增加了发生结直肠癌的风险。目的探讨结直肠癌家族史与结肠癌复发和生存的关系。设计、设置和研究对象：1999年4月至2001年5月参加CALGB 89803随机辅助化疗试验的1087例III期结肠癌患者的前瞻性观察研究。患者提供了基线的家族史数据，并进行了跟踪，直到2007年3月疾病复发和死亡(中位数随访，5.6年)。在一组患者中，我们评估了肿瘤标本中微卫星不稳定性(MSI)和错配修复(MMR)蛋白MLH1和MSH2的表达。主要结果根据是否有结直肠癌家族史来衡量无病生存率、无复发生存率和总生存率。结果在1087例符合条件的患者中，195例(17.9%)报告了一级亲属的结直肠癌家族史。195例有结直肠癌家族史的患者中有57例复发或死亡(29%，95%可信区间，23%-36%)，892例无家族史者中有343例复发或死亡(38%，95%可信区间，35%-42%)。与无家族史的患者相比，有1个或1个以上受累一级亲属的患者无病生存、无复发生存和总生存的调整风险比分别为0.72(95%CI，0.54~0.96)、0.74(95%CI，0.55~0.99)和0.75(95%CI，0.54~1.05)。随着受影响的一级亲属数量的增加，与家族史相关的癌症复发或死亡风险的降低变得更加明显。与没有结直肠癌家族史的参与者相比，那些有1个受影响亲属的患者无病生存的多变量HR为0.77(95%CI，0.57-1.04)。对于有2个或更多受影响亲属的参与者，我们观察到风险的更大降低(多变量HR无病生存，0.49；95%CI，0.23-1.04；P表示受影响亲属数量增加的趋势=。01)。结论在接受辅助化疗的III期结肠癌患者中，结直肠癌家族史与肿瘤复发和死亡率显著降低相关。
Context A family history of colorectal cancer in a first- degree relative increases the risk of developing colorectal cancer. However, the influence of family history on cancer recurrence and survival among patients with established disease remains uncertain.Objective To examine the association of family history of colorectal cancer with cancer recurrence and survival of patients with colon cancer.Design, Setting, and Participants Prospective observational study of 1087 patients with stage III colon cancer enrolled in a randomized adjuvant chemotherapy trial ( CALGB 89803) between April 1999 and May 2001. Patients provided data on family history at baseline and were followed up until March 2007 for disease recurrence and death ( median follow- up, 5.6 years). In a subset of patients, we assessed microsatellite instability ( MSI) and expression of the mismatch repair ( MMR) proteins MLH1 and MSH2 in tumor specimens.Main Outcome Measures Disease- free survival, recurrence- free survival, and overall survival according to the presence or absence of a family history of colorectal cancer.Results Among 1087 eligible patients, 195 ( 17.9%) reported a family history of colorectal cancer in a first- degree relative. Cancer recurrence or death occurred in 57 of 195 patients ( 29%; 95% confidence interval [ CI], 23%- 36%) with a family history of colorectal cancer and 343 of 892 patients ( 38%; 95% CI, 35%- 42%) without a family history. Compared with patients without a family history, the adjusted hazard ratios ( HRs) among those with 1 or more affected first- degree relatives were 0.72 ( 95% CI, 0.54- 0.96) for disease- free survival, 0.74 ( 95% CI, 0.55- 0.99) for recurrence- free survival, and 0.75 ( 95% CI, 0.54- 1.05) for overall survival. This reduction in risk of cancer recurrence or death associated with a family history became stronger with an increasing number of affected first- degree relatives. Compared with participants without a family history of colorectal cancer, those with 1 affected relative had a multivariate HR of 0.77 ( 95% CI, 0.57- 1.04) for disease- free survival. For participants with 2 or more affected relatives, we observed a greater reduction in risk ( multivariate HR for disease- free survival, 0.49; 95% CI, 0.23- 1.04; P for trend with increasing number of affected relatives=. 01). The improved disease- free survival associated with a family history was independent of tumoral MSI or MMR status.Conclusion Among patients with stage III colon cancer receiving adjuvant chemotherapy, a family history of colorectal cancer is associated with a significant reduction in cancer recurrence and death.