- 期刊
Risk of Colorectal and Gynecologic Cancer in Varied Degree Relatives of Lynch Syndrome and Lynch-like Syndrome Families
林奇氏症候群和類林奇氏症候群家族之不同程度親屬之大腸癌和婦科癌症的風險
摘要
Background. Hereditary nonpolyposis colorectal cancer (HNPCC) is an autosomal dominant genetic disorder caused by a variation in one of four DNA mismatch repair genes; such variations increase the risk of several cancers, including colon and endometrial cancer.However, limited research has examined the cancer risk among relatives of patients with HNPCC. This study analyzed the cancer risk among first-degree, second-degree, and third-degree relatives of patients with HNPCC. Methods. In this study, 50 patients with HNPCC, from 42 unrelated families, who met the Amsterdam-II criteria underwent testing for mismatch repair (MMR) expression; testing was conducted using next-generation sequencing for germline variations and immunohistochemical staining for MMR expression. Pedigree charts were constructed for families spanning at least three generations. The study population was then analyzed for clinical and histological features, pathogenic germline variations, and the rate of associated cancers among relatives of varying degrees of patients with Lynch and Lynch-like syndrome. Results. Among 715 identified relatives (225 first-degree, 291 second-degree, and 199 third-degree relatives), significant differences were observed in the rates of associated cancers across the three degrees of relationship (p < 0.001). The most common cancer types were colorectal and gynecologic cancers. Significant differences were observed in the rates of colorectal cancer (p < 0.001) and gynecologic cancer (p < 0.001) among first-degree, second-degree, and third-degree relatives. The cumulative incidence risk of colorectal cancer significantly differed between first-and second-degree relatives (p = 0.001), but the risk of gynecologic cancer was significantly different between first-degree and third-degree relatives (p = 0.026). Conclusion. This study demonstrated that in Lynch syndrome and Lynch-like syndrome patients, the incidence of colorectal cancer is significantly higher in first-degree relatives compared to second- and third-degree relatives. Moreover, in the case of gynecological cancer, the incidence rate is significantly higher in first-degree relatives than in third-degree relatives, but no significant difference is observed compared to second-degree relatives.
並列摘要
目的：遺傳性非息肉狀結直腸癌（HNPCC）是一種染色體顯性遺傳疾病，由四種DNA錯配修復基因中的變異引起；這些變異會增加多種癌症的風險，包括大腸直腸和子宮內膜癌等。然而目前對於HNPCC患者不同親等間親屬的癌症罹病風險研究有限。本研究分析了HNPCC患者的第一、二、三等親屬間的癌症罹病風險。方法：在本篇研究中，共有50位HNPCC患者符合Amsterdam criteria-II，其來自於不同的42個家庭。所有病患皆接受DNA錯配修復基因檢測，其使用次世代基因檢測及免疫組織化學染色法。研究中繪製了各病患的家族譜，紀錄至少第一、二、三等親屬間的罹病情形，近一步分析不同親等間的罹病風險。結果：共計715位親屬（225位一等親，291位二等親，199位三等親）納入了本研究，統計顯示不同親等間林奇氏症候群相關癌症的發病率存在顯著差異。其中最常見的癌症為大腸直腸癌及婦科癌症。在不同親等間，大腸直腸癌和婦科癌症的發病率也存在顯著差異。大腸直腸癌的累積發病風險在第一、二等親屬之間有顯著差異，而婦科癌症的風險在第一、三等親屬之間有顯著差異。結論：本篇文章旨在提供臨床醫師在診治林奇氏症候群患者及其親屬時，進一步了解不同程度親屬之癌症罹病的風險。