Lindor Noralane M, Rabe Kari, Petersen Gloria M, Haile Robert, Casey Graham, Baron John, Gallinger Steve, Bapat Bharati, Aronson Melyssa, Hopper John, Jass Jeremy, LeMarchand Loic, Grove John, Potter John, Newcomb Polly, Terdiman Jonathan P, Conrad Peggy, Moslein Gabriella, Goldberg Richard, Ziogas Argyrios, Anton-Culver Hoda, de Andrade Mariza, Siegmund Kim, Thibodeau Stephen N, Boardman Lisa A, Seminara Daniela
Department of Medical Genetics, Mayo Clinic, Rochester, Minn, USA.
JAMA. 2005 Apr 27;293(16):1979-85. doi: 10.1001/jama.293.16.1979.
Approximately 60% of families that meet the Amsterdam-I criteria (AC-I) for hereditary nonpolyposis colorectal cancer (HNPCC) have a hereditary abnormality in a DNA mismatch repair (MMR) gene. Cancer incidence in AC-I families with MMR gene mutations is reported to be very high, but cancer incidence for individuals in AC-I families with no evidence of an MMR defect is unknown.
To determine if cancer risks in AC-I families with no apparent deficiency in DNA MMR are different from cancer risks in AC-I families with DNA MMR abnormalities.
DESIGN, SETTING, AND PARTICIPANTS: Identification (1997-2001) of 161 AC-I pedigrees from multiple population- and clinic-based sources in North America and Germany, with families grouped into those with (group A) or without (group B) MMR deficiency by tumor testing. A total of 3422 relatives were included in the analyses.
Cancer incidence in groups A and B (excluding the 3 affected members used to define each pedigree as AC-I) and computed age- and sex-adjusted standardized incidence ratios (SIRs) using Surveillance, Epidemiology, and End Results data.
Group A families from both population- and clinic-based series showed increased incidence of the HNPCC-related cancers. Group B families showed increased incidence only for colorectal cancer (SIR, 2.3; 95% confidence interval, 1.7-3.0) and to a lesser extent than group A (SIR, 6.1; 95% confidence interval, 5.2-7.2) (P<.001).
Families who fulfill AC-I criteria but who have no evidence of a DNA MMR defect do not share the same cancer incidence as families with HNPCC-Lynch syndrome (ie, hereditary MMR deficiency). Relatives in such families have a lower incidence of colorectal cancer than those in families with HNPCC-Lynch syndrome, and incidence may not be increased for other cancers. These families should not be described or counseled as having HNPCC-Lynch syndrome. To facilitate distinguishing these entities, the designation of "familial colorectal cancer type X" is suggested to describe this type of familial aggregation of colorectal cancer.
约60%符合遗传性非息肉病性结直肠癌（HNPCC）阿姆斯特丹-I标准（AC-I）的家庭存在DNA错配修复（MMR）基因的遗传性异常。据报道，有MMR基因突变的AC-I家庭癌症发病率非常高，但无MMR缺陷证据的AC-I家庭中个体的癌症发病率尚不清楚。
确定DNA MMR无明显缺陷的AC-I家庭的癌症风险是否与存在DNA MMR异常的AC-I家庭的癌症风险不同。
设计、地点和参与者：1997年至2001年期间，从北美和德国多个基于人群和诊所的来源中识别出161个AC-I家系，通过肿瘤检测将家庭分为有MMR缺陷组（A组）和无MMR缺陷组（B组）。共有3422名亲属纳入分析。
A组和B组的癌症发病率（不包括用于将每个家系定义为AC-I的3名受影响成员），并使用监测、流行病学和最终结果数据计算年龄和性别调整后的标准化发病率（SIR）。
来自基于人群和诊所系列的A组家庭显示HNPCC相关癌症的发病率增加。B组家庭仅结直肠癌发病率增加（SIR，2.3；95%置信区间，1.7 - 3.0），且程度低于A组（SIR，6.1；95%置信区间，5.2 - 7.2）（P <.001）。
符合AC-I标准但无DNA MMR缺陷证据的家庭与HNPCC-Lynch综合征（即遗传性MMR缺陷）家庭的癌症发病率不同。此类家庭中的亲属结直肠癌发病率低于HNPCC-Lynch综合征家庭，其他癌症的发病率可能未增加。不应将这些家庭描述或咨询为患有HNPCC-Lynch综合征。为便于区分这些实体，建议使用“X型家族性结直肠癌”这一名称来描述这种结直肠癌的家族聚集类型。
