Tác động gia tăng của bảng SNP ung thư vú đối với phân loại rủi ro trong quần thể sàng lọc phụ nữ da trắng và người Mỹ gốc Phi

Springer Science and Business Media LLC - Tập 138 - Trang 889-898 - 2013
Anne Marie McCarthy1, Katrina Armstrong1,2, Elizabeth Handorf1, Leigh Boghossian2, Marisa Jones2, Jinbo Chen1, Mirar Bristol Demeter1, Erin McGuire1, Emily F. Conant1, Susan M. Domchek1,2
1Perelman School of Medicine, University of Pennsylvania, Philadelphia, USA
2Abramson Cancer Center, University of Pennsylvania, Philadelphia, USA

Tóm tắt

Dự đoán rủi ro ung thư vú vẫn chưa hoàn hảo, đặc biệt là ở các quần thể không phải người da trắng. Nghiên cứu này xem xét tác động của việc bao gồm các đột biến nucleotide đơn (SNP) vào dự đoán rủi ro cho phụ nữ da trắng và phụ nữ gốc Phi Mỹ trong quá trình sàng lọc chẩn đoán ung thư vú. Sử dụng một nghiên cứu đoàn hệ tiềm năng, thông tin rủi ro tiêu chuẩn và mẫu buccal đã được thu thập tại thời điểm chụp mammogram sàng lọc. Một panel 12 SNP đã được thực hiện bởi deCODE genetics. Rủi ro 5 năm và rủi ro suốt đời kết hợp SNP đã được tính bằng cách nhân rủi ro ước tính từ Công cụ Đánh giá Rủi ro Ung thư Vú (BCRAT) với tỷ lệ rủi ro di truyền tổng thể. Mức độ đồng thuận giữa BCRAT và mô hình kết hợp (BCRAT + SNPs) trong việc xác định phụ nữ có nguy cơ cao đã được đo bằng chỉ số kappa. Dữ liệu SNP có sẵn cho 810 phụ nữ (39% là người Mỹ gốc Phi, 55% là người da trắng). Rủi ro trung bình BCRAT 5 năm là 1.71% cho người da trắng và 1.18% cho người Mỹ gốc Phi. Tỷ lệ rủi ro di truyền trung bình là 1.09 ở người da trắng và 1.29 ở người Mỹ gốc Phi. Trong số phụ nữ da trắng, ba SNP có tần suất cao hơn, còn đối với phụ nữ Mỹ gốc Phi, bảy SNP có tần suất alen nguy cơ cao hơn và bốn SNP có tần suất nguy cơ thấp hơn so với số liệu đã báo cáo trước đó. Sự đồng thuận giữa BCRAT và mô hình kết hợp khá thấp trong việc xác định phụ nữ có nguy cơ cao (kappa 5 năm = 0.54, kappa suốt đời = 0.36). Việc thêm các SNP có tác động lớn nhất đối với phụ nữ gốc Phi Mỹ, trong đó 12.4% được xác định là có rủi ro cao 5 năm theo BCRAT, nhưng 33% theo mô hình kết hợp. Một tỷ lệ lớn hơn phụ nữ gốc Phi Mỹ đã được phân loại lại là có rủi ro cao 5 năm hơn phụ nữ da trắng khi sử dụng mô hình kết hợp (21 so với 10%). Việc thêm SNP vào BCRAT phân loại lại tình trạng nguy cơ cao của một số phụ nữ trong quá trình sàng lọc chẩn đoán ung thư vú, đặc biệt là phụ nữ Mỹ gốc Phi. Cần có thêm nghiên cứu để xác định tính hợp lệ và hữu ích lâm sàng của bảng SNP trong việc dự đoán rủi ro ung thư vú, đặc biệt là đối với người Mỹ gốc Phi, nhóm mà các alen rủi ro này thường chưa được xác thực.

Từ khóa

#ung thư vú #dự đoán rủi ro #SNP #nghiên cứu đoàn hệ #phụ nữ da trắng #phụ nữ gốc Phi Mỹ

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