2月13日，发表在《临床肿瘤学杂志》(Journal of Clinical Oncology)上的一项前瞻性研究显示，一种遗传性疾病——林奇综合征患者易患多种类型癌症，尤其是乳腺癌和胰腺癌风险均显著增加。
林奇综合征是一种常染色体显性遗传病，约占所有结直肠癌的5％～15％，既可见于癌症患者,也可见于尚无癌症者。该综合征定义为由错配修复(MMR)基因突变引起的对结直肠癌及某些其他癌症(如子宫内膜癌、胃癌)的遗传易感性。这些MMR基因突变以常染色体显性方式遗传,主要包括MLH1、MSH2、MSH6及PMS2基因突变,前二者较多见。
在化验血液时发现的这种常染色体显性遗传疾病是由4个DNA错配修复(MMR)基因(MLH1、MSH2、MSH6或PMS2)中的一个突变引起的。估计人群中携带频率为1/360~1/3,010，数值取决于计算中纳入所有4个特异性突变，还是纳入少于4个特异性突变。已知这种综合征可使多种类型癌症的风险增高，包括结肠癌。通常建议患者在较低年龄开始进行结肠镜检查，并以较一般人群更高的频率重复检查。但无突变的家庭成员无癌症风险增高，也不需要进行较一般人群更密集的筛查，原因尚未完全阐明。
研究者对1997-2010年间结肠癌家庭注册数据库中的446例突变携带者和1,029非携带者亲属进行了随访。几乎所有研究受试者(96%)为白人，女性比例略高于一半。入选时，不同亚组的平均年龄介于40~50岁之间。注册数据库包括来自美国、加拿大、澳大利亚和新西兰的受试者。
结果显示，经过中位数为5年的随访发现，突变携带者结肠癌、子宫内膜癌、卵巢癌、肾癌、胃癌和膀胱癌的风险分别为一般人群的20、31、19、11和10倍。乳腺癌和胰腺癌的风险分别增加了4倍和11倍。对于每种癌症类型，突变携带者的风险增加均具有高度统计学意义，P值介于0.009~<0.001之间。另外，林奇综合征患者通常在较一般人群更低的年龄被诊断出癌症(J. Clin. Oncol)。
研究者认为，对于MMR基因突变携带者的某些特殊部位癌症风险，应进行恰当的临床管理，如筛查性结肠镜检、预防性全子宫切除和双侧输卵管卵巢切除可能降低结直肠癌、子宫内膜癌和卵巢癌风险。（生物谷Bioon.com）
doi:10.1200/JCO.2011.39.5590
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Colorectal and Other Cancer Risks for Carriers and Noncarriers From Families With a DNA Mismatch Repair Gene Mutation: A Prospective Cohort Study
Aung Ko Win, Joanne P. Young, Noralane M. Lindor, Katherine M. Tucker, Dennis J. Ahnen, Graeme P. Young, Daniel D. Buchanan, Mark Clendenning, Graham G. Giles, Ingrid Winship, Finlay A. Macrae, Jack Goldblatt, Melissa C. Southey, Julie Arnold, Stephen N. Thibodeau, Shanaka R. Gunawardena, Bharati Bapat, John A. Baron, Graham Casey, Steven Gallinger, Lo?c Le Marchand, Polly A. Newcomb, Robert W. Haile, John L. Hopper and Mark A. Jenkins
Purpose To determine whether cancer risks for carriers and noncarriers from families with a mismatch repair (MMR) gene mutation are increased above the risks of the general population.
Patients and Methods We prospectively followed a cohort of 446 unaffected carriers of an MMR gene mutation (MLH1, n = 161; MSH2, n = 222; MSH6, n = 47; and PMS2, n = 16) and 1,029 their unaffected relatives who did not carry a mutation every 5 years at recruitment centers of the Colon Cancer Family Registry. For comparison of cancer risk with the general population, we estimated country-, age-, and sex-specific standardized incidence ratios (SIRs) of cancer for carriers and noncarriers.
Results Over a median follow-up of 5 years, mutation carriers had an increased risk of colorectal cancer (CRC; SIR, 20.48; 95% CI, 11.71 to 33.27; P < .001), endometrial cancer (SIR, 30.62; 95% CI, 11.24 to 66.64; P < .001), ovarian cancer (SIR, 18.81; 95% CI, 3.88 to 54.95; P < .001), renal cancer (SIR, 11.22; 95% CI, 2.31 to 32.79; P < .001), pancreatic cancer (SIR, 10.68; 95% CI, 2.68 to 47.70; P = .001), gastric cancer (SIR, 9.78; 95% CI, 1.18 to 35.30; P = .009), urinary bladder cancer (SIR, 9.51; 95% CI, 1.15 to 34.37; P = .009), and female breast cancer (SIR, 3.95; 95% CI, 1.59 to 8.13; P = .001). We found no evidence of their noncarrier relatives having an increased risk of any cancer, including CRC (SIR, 1.02; 95% CI, 0.33 to 2.39; P = .97).
Conclusion We confirmed that carriers of an MMR gene mutation were at increased risk of a wide variety of cancers, including some cancers not previously recognized as being a result of MMR mutations, and found no evidence of an increased risk of cancer for their noncarrier relatives.
