Douglas Julie A, Gruber Stephen B, Meister Karen A, Bonner Joseph, Watson Patrice, Krush Anne J, Lynch Henry T
Department of Human Genetics, University of Michigan Medical School, Ann Arbor 48109-0618, USA.
JAMA. 2005 Nov 2;294(17):2195-202. doi: 10.1001/jama.294.17.2195.
In 1895, Aldred Scott Warthin, MD, PhD, initiated one of the most thoroughly documented and longest cancer family histories ever recorded. The unusually high incidence and segregation of cancers of the colon, rectum, stomach, and endometrium in Dr Warthin's family G was later followed up by his colleagues, most recently by Henry Lynch, MD. Described today as a Lynch syndrome family, family G was last documented in 1971, prior to the modern era of molecular diagnostics.
To update family G.
DESIGN, SETTING, AND PARTICIPANTS: Historical prospective cohort study of family G members from 1895 to 2000.
The primary outcomes were the frequencies and types of cancers, ages at diagnosis, and presence of the T to G transversion at the splice acceptor site of exon 4 of the mutS homolog 2, colon cancer, nonpolyposis type 1 (E coli) (MSH2) gene in family G members. A secondary analysis compared cancer-specific incidence rates in family G with published national and regional cancer incidence rates through the standardized incidence ratio (SIR).
Family G now has 929 known descendants of the original progenitor first reported in 1913. Cancers of the colon and rectum (SIR, 3.20; 95% confidence interval [CI], 2.39-4.19) and endometrium (SIR, 3.51; 95% CI, 1.92-5.89) continue to predominate in family G. Five of 40 tested members of family G carry the MSH2 T to G mutation; as a result, 15 of their living relatives are at increased risk of developing 1 or more colorectal or Lynch syndrome-associated cancers. In contrast, 97 living members of family G can now be excluded as mutation carriers.
Within the last decade, molecular diagnostic testing has transformed the care of family G and other Lynch syndrome families in which a pathogenic mutation has been identified.
1895年，医学博士、哲学博士阿尔德雷德·斯科特·沃辛开创了有史以来记录最为详尽、历时最长的癌症家族病史之一。沃辛家族G中结肠癌、直肠癌、胃癌和子宫内膜癌异常高发且呈分离状态，其同事后来对该家族进行了跟进研究，最近的跟进者是医学博士亨利·林奇。如今被描述为林奇综合征家族的家族G，在1971年即分子诊断现代 era 之前最后一次被记录在案。
更新家族G的情况。
设计、地点和参与者：对1895年至2000年家族G成员进行的历史性前瞻性队列研究。
主要结局为家族G成员中癌症的频率和类型、诊断时的年龄，以及错配修复蛋白2（结肠癌，非息肉病1型（大肠杆菌））（MSH2）基因第4外显子剪接受体位点的T到G颠换情况。次要分析通过标准化发病比（SIR）将家族G中特定癌症的发病率与已发表的国家和地区癌症发病率进行比较。
家族G现在有929名已知的原始祖先的后代，该原始祖先于1913年首次被报道。结肠癌和直肠癌（SIR，3.20；95%置信区间[CI]，2.39 - 4.19）以及子宫内膜癌（SIR，3.51；95%CI，1.92 - 5.89）在家族G中仍然占主导地位。在接受检测的40名家族G成员中，有5人携带MSH2基因的T到G突变；因此，他们的15名在世亲属患1种或更多种结直肠癌或林奇综合征相关癌症的风险增加。相比之下，现在可以排除97名家族G在世成员为突变携带者。
在过去十年中，分子诊断检测改变了家族G以及其他已鉴定出致病突变的林奇综合征家族的治疗方式。
