Các mối liên hệ của biến thể đơn nucleotide với ung thư đại trực tràng nhầy: phân tích biến thể chung toàn bộ bộ gen và biến thể hiếm dựa trên gen

Biomarker Research - Tập 6 - Trang 1-10 - 2018
Michelle E. Penney1, Patrick S. Parfrey2, Sevtap Savas1,3, Yildiz E. Yilmaz1,2,4
1Discipline of Genetics, Faculty of Medicine, Memorial University of Newfoundland, St. John’s, Canada
2Discipline of Medicine, Faculty of Medicine, Memorial University of Newfoundland, St. John’s, Canada
3Discipline of Oncology, Faculty of Medicine, Memorial University of Newfoundland, St. John’s, Canada
4Department of Mathematics and Statistics, Faculty of Science, Memorial University of Newfoundland, St. John’s, Canada

Tóm tắt

Ung thư đại trực tràng có tác động đáng kể đến cá nhân và hệ thống chăm sóc sức khỏe. Nhiều gen đã được xác định ảnh hưởng đến quá trình sinh bệnh của nó. Tuy nhiên, cơ sở di truyền của mô học khối u nhầy, một loại phụ ác tính của ung thư đại trực tràng, hiện vẫn chưa được biết đến nhiều. Nghiên cứu này nhằm xác định các biến thể di truyền chung và hiếm có liên quan đến kiểu hình khối u nhầy. Dữ liệu biến thể nucleotide đơn (SNP) toàn bộ bộ gen đã được nghiên cứu trên một nhóm bệnh nhân ung thư đại trực tràng (n = 505). Các phân tích liên kết đã được thực hiện cho 729,373 SNP chung và 275,645 SNP hiếm. Phân tích liên kết SNP chung được thực hiện bằng cách sử dụng hồi quy logistic đơn biến và đa biến dưới các mô hình di truyền khác nhau. Phân tích liên kết biến thể hiếm được thực hiện bằng cách sử dụng một bài kiểm tra nhiều dấu hiệu. Không có liên kết nào đạt được ý nghĩa toàn bộ bộ gen truyền thống. Tuy nhiên, những liên kết di truyền đầy hứa hẹn đã được xác định. Các SNP chung đã xác định cải thiện đáng kể độ chính xác phân biệt của mô hình cho kiểu hình khối u nhầy. Cụ thể, diện tích dưới đường cong tính năng hoạt động của người nhận (ROC) đã tăng từ 0.703 (95% CI: 0.634–0.773) lên 0.916 (95% CI: 0.873–0.960) khi xem xét các SNP có ý nghĩa nhất. Ngoài ra, phân tích biến thể hiếm xác định một số vùng di truyền có thể chứa các biến thể hiếm nguyên nhân có liên quan đến kiểu hình khối u nhầy. Đây là nghiên cứu đầu tiên áp dụng cả phân tích biến thể chung và hiếm để xác định các liên kết di truyền với kiểu hình khối u nhầy sử dụng dữ liệu kiểu gen toàn bộ bộ gen. Kết quả của chúng tôi gợi ý những liên kết mới với khối u nhầy. Khi được xác nhận, các kết quả này sẽ không chỉ giúp chúng ta hiểu các cơ sở sinh học của mô học nhầy, mà còn có thể giúp phát triển các lựa chọn điều trị nhắm mục tiêu cho các khối u nhầy.

Từ khóa


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