Development of polygenic risk scores for South East Asian populations to identify women at higher-risk of breast cancer

为东南亚人群制定多基因风险评分，以确定患乳腺癌风险较高的女性

• 批准号: MR/P012930/1
• 负责人: Antonis Antoniou
• 金额: $ 52.08万
• 依托单位: University of Cambridge
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2017
• 资助国家: 英国
• 起止时间: 2017 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FP012930%2F1
• 关键词: Development; polygenic; risk; scores; South

Breast cancer burden is large and growing in Asia. In Malaysia, the breast cancer incidence has increased rapidly for the past two decades, albeit that it is still less than half of that in Europeans. The rapid increased incidence has been associated with changing lifestyle, such as decreased parity, no/short period of breastfeeding, and increasing Westernisation and urbanization. Breast cancer is now the most common cancer across all ethnicities in Malaysia, accounting for 31% of cancers in women, and it is the most common cause of cancer-related deaths. Early detection by screening can reduce breast cancer mortality. However, due to lack of funding within the national health services and lack of justification for population-based screening, only opportunistic screening is practiced. This is suboptimal and inequitable. A viable alternative approach is to improve screening strategies by identifying high-risk women who should be targeted for screening. In this proposal, we plan to bring technological advances in the understanding of breast cancer genetics to develop tools that can be used identify women who are at higher risk of developing breast cancer so that early detection and disease prevention interventions become possible. The findings of this research will inform the development of appropriate management to ensure that healthcare resources can be used efficiently for targeted screening and prevention.

乳腺癌负担在亚洲很大，而且还在增长。在马来西亚，乳腺癌发病率在过去二十年中迅速增加，尽管仍不到欧洲人的一半。发病率的迅速增加与生活方式的改变有关，例如产次减少、没有母乳喂养/母乳喂养时间短以及西方化和城市化的增加。乳腺癌现在是马来西亚所有种族中最常见的癌症，占女性癌症的31%，也是癌症相关死亡的最常见原因。通过筛查早期发现可以降低乳腺癌死亡率。然而，由于国家卫生服务机构缺乏资金，缺乏基于人群的筛查的理由，只能进行机会性筛查。这是次优和不公平的。一个可行的替代方法是通过确定应该进行筛查的高危妇女来改进筛查策略。在这项提案中，我们计划将技术进步引入对乳腺癌遗传学的理解，以开发可用于识别患乳腺癌风险较高的女性的工具，从而使早期检测和疾病预防干预成为可能。这项研究的结果将为制定适当的管理提供信息，以确保医疗资源可以有效地用于有针对性的筛查和预防。

项目成果

Overlap of high-risk individuals predicted by family history, and genetic and non-genetic breast cancer risk prediction models: implications for risk stratification.

• DOI: 10.1186/s12916-022-02334-z
• 发表时间: 2022-04-26
• 期刊: BMC MEDICINE
• 影响因子: 9.3
• 作者: Ho, Peh Joo;Ho, Weang Kee;Khng, Alexis J.;Yeoh, Yen Shing;Tan, Benita Kiat-Tee;Tan, Ern Yu;Lim, Geok Hoon;Tan, Su-Ming;Tan, Veronique Kiak Mien;Yip, Cheng-Har;Mohd-Taib, Nur-Aishah;Wong, Fuh Yong;Lim, Elaine Hsuen;Ngeow, Joanne;Chay, Wen Yee;Leong, Lester Chee Hao;Yong, Wei Sean;Seah, Chin Mui;Tang, Siau Wei;Ng, Celene Wei Qi;Yan, Zhiyan;Lee, Jung Ah;Rahmat, Kartini;Islam, Tania;Hassan, Tiara;Tai, Mei-Chee;Khor, Chiea Chuen;Yuan, Jian-Min;Koh, Woon-Puay;Sim, Xueling;Dunning, Alison M.;Bolla, Manjeet K.;Antoniou, Antonis C.;Teo, Soo-Hwang;Li, Jingmei;Hartman, Mikael
• 通讯作者: Hartman, Mikael

Breast Cancer Risk Genes - Association Analysis in More than 113,000 Women.

• DOI: 10.1056/nejmoa1913948
• 发表时间: 2021-02-04
• 期刊: The New England journal of medicine
• 作者: Breast Cancer Association Consortium;Dorling L;Carvalho S;Allen J;González-Neira A;Luccarini C;Wahlström C;Pooley KA;Parsons MT;Fortuno C;Wang Q;Bolla MK;Dennis J;Keeman R;Alonso MR;Álvarez N;Herraez B;Fernandez V;Núñez-Torres R;Osorio A;Valcich J;Li M;Törngren T;Harrington PA;Baynes C;Conroy DM;Decker B;Fachal L;Mavaddat N;Ahearn T;Aittomäki K;Antonenkova NN;Arnold N;Arveux P;Ausems MGEM;Auvinen P;Becher H;Beckmann MW;Behrens S;Bermisheva M;Białkowska K;Blomqvist C;Bogdanova NV;Bogdanova-Markov N;Bojesen SE;Bonanni B;Børresen-Dale AL;Brauch H;Bremer M;Briceno I;Brüning T;Burwinkel B;Cameron DA;Camp NJ;Campbell A;Carracedo A;Castelao JE;Cessna MH;Chanock SJ;Christiansen H;Collée JM;Cordina-Duverger E;Cornelissen S;Czene K;Dörk T;Ekici AB;Engel C;Eriksson M;Fasching PA;Figueroa J;Flyger H;Försti A;Gabrielson M;Gago-Dominguez M;Georgoulias V;Gil F;Giles GG;Glendon G;Garcia EBG;Alnæs GIG;Guénel P;Hadjisavvas A;Haeberle L;Hahnen E;Hall P;Hamann U;Harkness EF;Hartikainen JM;Hartman M;He W;Heemskerk-Gerritsen BAM;Hillemanns P;Hogervorst FBL;Hollestelle A;Ho WK;Hooning MJ;Howell A;Humphreys K;Idris F;Jakubowska A;Jung A;Kapoor PM;Kerin MJ;Khusnutdinova E;Kim SW;Ko YD;Kosma VM;Kristensen VN;Kyriacou K;Lakeman IMM;Lee JW;Lee MH;Li J;Lindblom A;Lo WY;Loizidou MA;Lophatananon A;Lubiński J;MacInnis RJ;Madsen MJ;Mannermaa A;Manoochehri M;Manoukian S;Margolin S;Martinez ME;Maurer T;Mavroudis D;McLean C;Meindl A;Mensenkamp AR;Michailidou K;Miller N;Mohd Taib NA;Muir K;Mulligan AM;Nevanlinna H;Newman WG;Nordestgaard BG;Ng PS;Oosterwijk JC;Park SK;Park-Simon TW;Perez JIA;Peterlongo P;Porteous DJ;Prajzendanc K;Prokofyeva D;Radice P;Rashid MU;Rhenius V;Rookus MA;Rüdiger T;Saloustros E;Sawyer EJ;Schmutzler RK;Schneeweiss A;Schürmann P;Shah M;Sohn C;Southey MC;Surowy H;Suvanto M;Thanasitthichai S;Tomlinson I;Torres D;Truong T;Tzardi M;Valova Y;van Asperen CJ;Van Dam RM;van den Ouweland AMW;van der Kolk LE;van Veen EM;Wendt C;Williams JA;Yang XR;Yoon SY;Zamora MP;Evans DG;de la Hoya M;Simard J;Antoniou AC;Borg Å;Andrulis IL;Chang-Claude J;García-Closas M;Chenevix-Trench G;Milne RL;Pharoah PDP;Schmidt MK;Spurdle AB;Vreeswijk MPG;Benitez J;Dunning AM;Kvist A;Teo SH;Devilee P;Easton DF
• 通讯作者: Easton DF

Predicting the Likelihood of Carrying a BRCA1 or BRCA2 Mutation in Asian Patients With Breast Cancer.

• DOI: 10.1200/jco.21.01647
• 发表时间: 2022-05-10
• 期刊: Journal of clinical oncology : official journal of the American Society of Clinical Oncology
• 作者: Ang BH;Ho WK;Wijaya E;Kwan PY;Ng PS;Yoon SY;Hasan SN;Lim JMC;Hassan T;Tai MC;Allen J;Lee A;Taib NAM;Yip CH;Hartman M;Lim SH;Tan EY;Tan BKT;Tan SM;Tan VKM;Ho PJ;Khng AJ;Dunning AM;Li J;Easton DF;Antoniou AC;Teo SH
• 通讯作者: Teo SH

Polygenic risk scores for prediction of breast cancer risk in Asian populations.

• DOI: 10.1016/j.gim.2021.11.008
• 发表时间: 2022-03
• 期刊: Genetics in medicine : official journal of the American College of Medical Genetics
• 作者: Ho WK;Tai MC;Dennis J;Shu X;Li J;Ho PJ;Millwood IY;Lin K;Jee YH;Lee SH;Mavaddat N;Bolla MK;Wang Q;Michailidou K;Long J;Wijaya EA;Hassan T;Rahmat K;Tan VKM;Tan BKT;Tan SM;Tan EY;Lim SH;Gao YT;Zheng Y;Kang D;Choi JY;Han W;Lee HB;Kubo M;Okada Y;Namba S;BioBank Japan Project;Park SK;Kim SW;Shen CY;Wu PE;Park B;Muir KR;Lophatananon A;Wu AH;Tseng CC;Matsuo K;Ito H;Kwong A;Chan TL;John EM;Kurian AW;Iwasaki M;Yamaji T;Kweon SS;Aronson KJ;Murphy RA;Koh WP;Khor CC;Yuan JM;Dorajoo R;Walters RG;Chen Z;Li L;Lv J;Jung KJ;Kraft P;Pharoah PDB;Dunning AM;Simard J;Shu XO;Yip CH;Taib NAM;Antoniou AC;Zheng W;Hartman M;Easton DF;Teo SH
• 通讯作者: Teo SH