Kastrinos Fay, Mukherjee Bhramar, Tayob Nabihah, Wang Fei, Sparr Jennifer, Raymond Victoria M, Bandipalliam Prathap, Stoffel Elena M, Gruber Stephen B, Syngal Sapna
Department of Internal Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.
JAMA. 2009 Oct 28;302(16):1790-5. doi: 10.1001/jama.2009.1529.
Lynch syndrome is an inherited cause of colorectal cancer caused by mutations of DNA mismatch repair (MMR) genes. A number of extracolonic tumors have been associated with the disorder, including pancreatic cancer; however, the risk of pancreatic cancer in Lynch syndrome is uncertain and not quantified.
To estimate pancreatic cancer risk in families with germline MMR gene mutations.
DESIGN, SETTING, AND PATIENTS: Cancer histories of probands and their relatives were evaluated in MMR gene mutation carriers in the familial cancer registries of the Dana-Farber Cancer Institute (n = 80), Boston, Massachusetts, and University of Michigan Comprehensive Cancer Center (n = 67), Ann Arbor, Michigan. Families enrolled before the study start date (June 2008) were eligible. Age-specific cumulative risks and hazard ratio estimates of pancreatic cancer risk were calculated and compared with the general population using modified segregation analysis, with correction for ascertainment.
Age-specific cumulative risks and hazard ratio estimates of pancreatic cancer risk.
Data on 6342 individuals from 147 families with MMR gene mutations were analyzed. Thirty-one families (21.1%) reported at least 1 case of pancreatic cancer. Forty-seven pancreatic cancers were reported (21 men and 26 women), with no sex-related difference in age of diagnosis (51.5 vs 56.5 years for men and women, respectively). The cumulative risk of pancreatic cancer in these families with gene mutations was 1.31% (95% confidence interval [CI], 0.31%-2.32%) up to age 50 years and 3.68% (95% CI, 1.45%-5.88%) up to age 70 years, which represents an 8.6-fold increase (95% CI, 4.7-15.7) compared with the general population.
Among 147 families with germline MMR gene mutations, the risk of pancreatic cancer was increased compared with the US population. Individuals with MMR gene mutations and a family history of pancreatic cancer are appropriate to include in studies to further define the risk of premalignant and malignant pancreatic neoplasms and potential benefits and limitations of surveillance.
林奇综合征是一种由DNA错配修复（MMR）基因突变引起的遗传性结直肠癌病因。许多结肠外肿瘤与该疾病有关，包括胰腺癌；然而，林奇综合征患者患胰腺癌的风险尚不确定且未被量化。
评估携带种系MMR基因突变的家族中患胰腺癌的风险。
设计、地点和患者：在马萨诸塞州波士顿的达纳-法伯癌症研究所（n = 80）和密歇根大学综合癌症中心（n = 67）的家族癌症登记处，对先证者及其亲属的癌症病史进行了评估，这些登记处的患者均为MMR基因突变携带者。在研究开始日期（2008年6月）之前登记的家族符合条件。使用改良的分离分析计算了特定年龄的胰腺癌累积风险和风险比估计值，并与一般人群进行了比较，同时对确诊进行了校正。
特定年龄的胰腺癌累积风险和风险比估计值。
分析了来自147个携带MMR基因突变家族的6342名个体的数据。31个家族（21.1%）报告至少有1例胰腺癌。共报告了47例胰腺癌（21名男性和26名女性），诊断年龄无性别差异（男性和女性分别为51.5岁和56.5岁）。这些基因突变家族中，50岁时胰腺癌的累积风险为1.31%（95%置信区间[CI]，0.31%-2.32%），70岁时为3.68%（95%CI，1.45%-5.88%），与一般人群相比增加了8.6倍（95%CI，4.7-15.7）。
在147个携带种系MMR基因突变的家族中，胰腺癌风险高于美国人群。携带MMR基因突变且有胰腺癌家族史的个体适合纳入研究，以进一步明确胰腺癌前病变和恶性肿瘤的风险以及监测的潜在益处和局限性。
