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  1. Article ; Online: Communication about positive BRCA1 and BRCA2 genetic test results and uptake of testing in relatives in a diverse Asian setting.

    Lee, Daphne S-C / Meiser, Bettina / Mariapun, Shivaani / Hassan, Tiara / Yip, Cheng-Har / Mohd Taib, Nur A / Teo, Soo-Hwang / Thong, Meow-Keong / Yoon, Sook-Yee

    Journal of genetic counseling

    2020  Volume 30, Issue 3, Page(s) 720–729

    Abstract: The vast majority of studies assessing communication of BRCA1/2 results with relatives and family uptake of BRCA1/2 testing have been conducted in Western societies, and a dearth of studies have been conducted in Asia among relatives of diverse carriers ... ...

    Abstract The vast majority of studies assessing communication of BRCA1/2 results with relatives and family uptake of BRCA1/2 testing have been conducted in Western societies, and a dearth of studies have been conducted in Asia among relatives of diverse carriers of pathogenic BRCA1/2 germline variants. This study aimed to present rates of BRCA1/2 result disclosure by probands and probands' motivators and barriers of family communication and predictive testing uptake among eligible relatives. It also examined patterns of disclosure and testing uptake among different types of relatives. Eighty-seven carriers with either breast or ovarian cancer, who had previously been found to be carriers of a pathogenic variant in BRCA1/2, were interviewed over the phone using a semi-structured interview guide. Fifty-six percent of patients were Chinese, 21% were Indian, and 23% were Malay. It was found that 62.0% of eligible first- and second-degree relatives were informed by the proband about the testing result and that 11.5% of eligible first- and second-degree relatives had genetic testing. First-degree relatives were more likely to have been informed and tested compared to second-degree relatives, as were sisters compared to brothers. The low rates of family communication and testing uptake documented in this study suggest that interventions should focus on encouraging probands to inform male and second-degree relatives and targeting such relatives to increase informed decisions and accessibility to testing. Promotion strategies should be culturally sensitive to optimize outcomes.
    MeSH term(s) BRCA1 Protein/genetics ; BRCA2 Protein/genetics ; Breast Neoplasms/genetics ; Communication ; Disclosure ; Female ; Genetic Predisposition to Disease ; Genetic Testing ; Humans ; Male ; Mutation ; Ovarian Neoplasms/diagnosis ; Ovarian Neoplasms/genetics
    Chemical Substances BRCA1 Protein ; BRCA1 protein, human ; BRCA2 Protein ; BRCA2 protein, human
    Language English
    Publishing date 2020-11-27
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1117799-8
    ISSN 1573-3599 ; 1059-7700
    ISSN (online) 1573-3599
    ISSN 1059-7700
    DOI 10.1002/jgc4.1360
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Comparable frequency of BRCA1, BRCA2 and TP53 germline mutations in a multi-ethnic Asian cohort suggests TP53 screening should be offered together with BRCA1/2 screening to early-onset breast cancer patients.

    Lee, Daphne S C / Yoon, Sook-Yee / Looi, Lai Meng / Kang, Peter / Kang, In Nee / Sivanandan, Kavitta / Ariffin, Hany / Thong, Meow Keong / Chin, Kin Fah / Mohd Taib, Nur Aishah / Yip, Cheng-Har / Teo, Soo-Hwang

    Breast cancer research : BCR

    2012  Volume 14, Issue 2, Page(s) R66

    Abstract: Introduction: Germline TP53 mutations cause an increased risk to early-onset breast cancer in Li-Fraumeni syndrome (LFS) families and the majority of carriers identified through breast cancer cohorts have LFS or Li-Fraumeni-like (LFL) features. However, ...

    Abstract Introduction: Germline TP53 mutations cause an increased risk to early-onset breast cancer in Li-Fraumeni syndrome (LFS) families and the majority of carriers identified through breast cancer cohorts have LFS or Li-Fraumeni-like (LFL) features. However, in Asia and in many low resource settings, it is challenging to obtain accurate family history and we, therefore, sought to determine whether the presence of early-onset breast cancer is an appropriate selection criteria for germline TP53 testing.
    Methods: A total of 100 patients with early-onset breast cancer (≤ 35 years) treated at University Malaya Medical Centre between 2003 and 2009, were analyzed for germline mutations in BRCA1, BRCA2 and TP53 by full DNA sequencing. Of the mutations identified, we examined their likely pathogenicity on the basis of prevalence in a case-control cohort, co-segregation analyses and loss of heterozygosity (LOH) in tumor tissues.
    Results: We identified 11 BRCA1 (11%) and 6 BRCA2 (6%) germline carriers among early-onset breast cancer patients. Of the 83 BRCA-negative patients, we identified four exonic variants and three intronic variants in TP53. Of these, two exonic variants are clinically relevant (E346X and p. G334_R335dup6) and two novel missense mutations (A138V and E285K) are likely to be clinically relevant, on the basis of co-segregation and loss of heterozygosity (LOH). Notably, E285K was found in two unrelated individuals and haplotype analyses suggest a founder effect. Two of the three intronic variants are likely benign based on their prevalence in a control population. Clinically relevant TP53 germline mutations were identified in three of the four patients (75%) with a family history of at least two LFS-linked cancers (breast, bone or soft tissue sarcoma, brain tumors or adrenocortical cancer); 1 of the 17 patients (6%) with a family history of breast cancer only, and 1 of the 62 patients (< 2%) with no family history of breast or LFS-linked cancers.
    Conclusions: Our study reports germline BRCA1, BRCA2 and TP53 mutations are found in early-onset breast cancer patients at 11%, 6% and 5% respectively, suggesting that TP53 mutation screening should be considered for these patients. However, we find that even in low resource Asian settings where family history is poorly reported, germline TP53 mutations are found predominantly among breast cancer patients with a family history of LFS-linked cancers.
    MeSH term(s) Adult ; Age of Onset ; BRCA1 Protein/genetics ; BRCA2 Protein/genetics ; Breast Neoplasms/epidemiology ; Breast Neoplasms/genetics ; Case-Control Studies ; Cohort Studies ; Female ; Genetic Predisposition to Disease ; Genetic Testing ; Germ-Line Mutation ; Humans ; Li-Fraumeni Syndrome/genetics ; Loss of Heterozygosity ; Malaysia/epidemiology ; Malaysia/ethnology ; Sarcoma/genetics ; Tumor Suppressor Protein p53/genetics
    Chemical Substances BRCA1 Protein ; BRCA2 Protein ; BRCA2 protein, human ; Tumor Suppressor Protein p53
    Language English
    Publishing date 2012-04-16
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2015059-3
    ISSN 1465-542X ; 1465-5411
    ISSN (online) 1465-542X
    ISSN 1465-5411
    DOI 10.1186/bcr3172
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Publisher Correction: Evidence that breast cancer risk at the 2q35 locus is mediated through IGFBP5 regulation.

    Ghoussaini, Maya / Edwards, Stacey L / Michailidou, Kyriaki / Nord, Silje / Cowper-Sal Lari, Richard / Desai, Kinjal / Kar, Siddhartha / Hillman, Kristine M / Kaufmann, Susanne / Glubb, Dylan M / Beesley, Jonathan / Dennis, Joe / Bolla, Manjeet K / Wang, Qin / Dicks, Ed / Guo, Qi / Schmidt, Marjanka K / Shah, Mitul / Luben, Robert /
    Brown, Judith / Czene, Kamila / Darabi, Hatef / Eriksson, Mikael / Klevebring, Daniel / Bojesen, Stig E / Nordestgaard, Børge G / Nielsen, Sune F / Flyger, Henrik / Lambrechts, Diether / Thienpont, Bernard / Neven, Patrick / Wildiers, Hans / Broeks, Annegien / Van't Veer, Laura J / Rutgers, Emiel J Th / Couch, Fergus J / Olson, Janet E / Hallberg, Emily / Vachon, Celine / Chang-Claude, Jenny / Rudolph, Anja / Seibold, Petra / Flesch-Janys, Dieter / Peto, Julian / Dos-Santos-Silva, Isabel / Gibson, Lorna / Nevanlinna, Heli / Muranen, Taru A / Aittomäki, Kristiina / Blomqvist, Carl / Hall, Per / Li, Jingmei / Liu, Jianjun / Humphreys, Keith / Kang, Daehee / Choi, Ji-Yeob / Park, Sue K / Noh, Dong-Young / Matsuo, Keitaro / Ito, Hidemi / Iwata, Hiroji / Yatabe, Yasushi / Guénel, Pascal / Truong, Thérèse / Menegaux, Florence / Sanchez, Marie / Burwinkel, Barbara / Marme, Frederik / Schneeweiss, Andreas / Sohn, Christof / Wu, Anna H / Tseng, Chiu-Chen / Van Den Berg, David / Stram, Daniel O / Benitez, Javier / Pilar Zamora, M / Perez, Jose Ignacio Arias / Menéndez, Primitiva / Shu, Xiao-Ou / Lu, Wei / Gao, Yu-Tang / Cai, Qiuyin / Cox, Angela / Cross, Simon S / Reed, Malcolm W R / Andrulis, Irene L / Knight, Julia A / Glendon, Gord / Tchatchou, Sandrine / Sawyer, Elinor J / Tomlinson, Ian / Kerin, Michael J / Miller, Nicola / Haiman, Christopher A / Henderson, Brian E / Schumacher, Fredrick / Le Marchand, Loic / Lindblom, Annika / Margolin, Sara / Teo, Soo Hwang / Yip, Cheng Har / Lee, Daphne S C / Wong, Tien Y / Hooning, Maartje J / Martens, John W M / Collée, J Margriet / van Deurzen, Carolien H M / Hopper, John L / Southey, Melissa C / Tsimiklis, Helen / Kapuscinski, Miroslav K / Shen, Chen-Yang / Wu, Pei-Ei / Yu, Jyh-Cherng / Chen, Shou-Tung / Alnæs, Grethe Grenaker / Borresen-Dale, Anne-Lise / Giles, Graham G / Milne, Roger L / McLean, Catriona / Muir, Kenneth / Lophatananon, Artitaya / Stewart-Brown, Sarah / Siriwanarangsan, Pornthep / Hartman, Mikael / Miao, Hui / Buhari, Shaik Ahmad Bin Syed / Teo, Yik Ying / Fasching, Peter A / Haeberle, Lothar / Ekici, Arif B / Beckmann, Matthias W / Brenner, Hermann / Dieffenbach, Aida Karina / Arndt, Volker / Stegmaier, Christa / Swerdlow, Anthony / Ashworth, Alan / Orr, Nick / Schoemaker, Minouk J / García-Closas, Montserrat / Figueroa, Jonine / Chanock, Stephen J / Lissowska, Jolanta / Simard, Jacques / Goldberg, Mark S / Labrèche, France / Dumont, Martine / Winqvist, Robert / Pylkäs, Katri / Jukkola-Vuorinen, Arja / Brauch, Hiltrud / Brüning, Thomas / Koto, Yon-Dschun / Radice, Paolo / Peterlongo, Paolo / Bonanni, Bernardo / Volorio, Sara / Dörk, Thilo / Bogdanova, Natalia V / Helbig, Sonja / Mannermaa, Arto / Kataja, Vesa / Kosma, Veli-Matti / Hartikainen, Jaana M / Devilee, Peter / Tollenaar, Robert A E M / Seynaeve, Caroline / Van Asperen, Christi J / Jakubowska, Anna / Lubinski, Jan / Jaworska-Bieniek, Katarzyna / Durda, Katarzyna / Slager, Susan / Toland, Amanda E / Ambrosone, Christine B / Yannoukakos, Drakoulis / Sangrajrang, Suleeporn / Gaborieau, Valerie / Brennan, Paul / McKay, James / Hamann, Ute / Torres, Diana / Zheng, Wei / Long, Jirong / Anton-Culver, Hoda / Neuhausen, Susan L / Luccarini, Craig / Baynes, Caroline / Ahmed, Shahana / Maranian, Mel / Healey, Catherine S / González-Neira, Anna / Pita, Guillermo / Rosario Alonso, M / Álvarez, Nuria / Herrero, Daniel / Tessier, Daniel C / Vincent, Daniel / Bacot, Francois / de Santiago, Ines / Carroll, Jason / Caldas, Carlos / Brown, Melissa A / Lupien, Mathieu / Kristensen, Vessela N / Pharoah, Paul D P / Chenevix-Trench, Georgia / French, Juliet D / Easton, Douglas F / Dunning, Alison M

    Nature communications

    2018  Volume 9, Page(s) 16193

    Abstract: This corrects the article DOI: 10.1038/ncomms5999. ...

    Abstract This corrects the article DOI: 10.1038/ncomms5999.
    Language English
    Publishing date 2018-04-10
    Publishing country England
    Document type Journal Article ; Published Erratum
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/ncomms16193
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Evidence that breast cancer risk at the 2q35 locus is mediated through IGFBP5 regulation.

    Ghoussaini, Maya / Edwards, Stacey L / Michailidou, Kyriaki / Nord, Silje / Cowper-Sal Lari, Richard / Desai, Kinjal / Kar, Siddhartha / Hillman, Kristine M / Kaufmann, Susanne / Glubb, Dylan M / Beesley, Jonathan / Dennis, Joe / Bolla, Manjeet K / Wang, Qin / Dicks, Ed / Guo, Qi / Schmidt, Marjanka K / Shah, Mitul / Luben, Robert /
    Brown, Judith / Czene, Kamila / Darabi, Hatef / Eriksson, Mikael / Klevebring, Daniel / Bojesen, Stig E / Nordestgaard, Børge G / Nielsen, Sune F / Flyger, Henrik / Lambrechts, Diether / Thienpont, Bernard / Neven, Patrick / Wildiers, Hans / Broeks, Annegien / Van't Veer, Laura J / Th Rutgers, Emiel J / Couch, Fergus J / Olson, Janet E / Hallberg, Emily / Vachon, Celine / Chang-Claude, Jenny / Rudolph, Anja / Seibold, Petra / Flesch-Janys, Dieter / Peto, Julian / Dos-Santos-Silva, Isabel / Gibson, Lorna / Nevanlinna, Heli / Muranen, Taru A / Aittomäki, Kristiina / Blomqvist, Carl / Hall, Per / Li, Jingmei / Liu, Jianjun / Humphreys, Keith / Kang, Daehee / Choi, Ji-Yeob / Park, Sue K / Noh, Dong-Young / Matsuo, Keitaro / Ito, Hidemi / Iwata, Hiroji / Yatabe, Yasushi / Guénel, Pascal / Truong, Thérèse / Menegaux, Florence / Sanchez, Marie / Burwinkel, Barbara / Marme, Frederik / Schneeweiss, Andreas / Sohn, Christof / Wu, Anna H / Tseng, Chiu-Chen / Van Den Berg, David / Stram, Daniel O / Benitez, Javier / Zamora, M Pilar / Perez, Jose Ignacio Arias / Menéndez, Primitiva / Shu, Xiao-Ou / Lu, Wei / Gao, Yu-Tang / Cai, Qiuyin / Cox, Angela / Cross, Simon S / Reed, Malcolm W R / Andrulis, Irene L / Knight, Julia A / Glendon, Gord / Tchatchou, Sandrine / Sawyer, Elinor J / Tomlinson, Ian / Kerin, Michael J / Miller, Nicola / Haiman, Christopher A / Henderson, Brian E / Schumacher, Fredrick / Le Marchand, Loic / Lindblom, Annika / Margolin, Sara / Teo, Soo Hwang / Yip, Cheng Har / Lee, Daphne S C / Wong, Tien Y / Hooning, Maartje J / Martens, John W M / Collée, J Margriet / van Deurzen, Carolien H M / Hopper, John L / Southey, Melissa C / Tsimiklis, Helen / Kapuscinski, Miroslav K / Shen, Chen-Yang / Wu, Pei-Ei / Yu, Jyh-Cherng / Chen, Shou-Tung / Alnæs, Grethe Grenaker / Borresen-Dale, Anne-Lise / Giles, Graham G / Milne, Roger L / McLean, Catriona / Muir, Kenneth / Lophatananon, Artitaya / Stewart-Brown, Sarah / Siriwanarangsan, Pornthep / Hartman, Mikael / Miao, Hui / Buhari, Shaik Ahmad Bin Syed / Teo, Yik Ying / Fasching, Peter A / Haeberle, Lothar / Ekici, Arif B / Beckmann, Matthias W / Brenner, Hermann / Dieffenbach, Aida Karina / Arndt, Volker / Stegmaier, Christa / Swerdlow, Anthony / Ashworth, Alan / Orr, Nick / Schoemaker, Minouk J / García-Closas, Montserrat / Figueroa, Jonine / Chanock, Stephen J / Lissowska, Jolanta / Simard, Jacques / Goldberg, Mark S / Labrèche, France / Dumont, Martine / Winqvist, Robert / Pylkäs, Katri / Jukkola-Vuorinen, Arja / Brauch, Hiltrud / Brüning, Thomas / Koto, Yon-Dschun / Radice, Paolo / Peterlongo, Paolo / Bonanni, Bernardo / Volorio, Sara / Dörk, Thilo / Bogdanova, Natalia V / Helbig, Sonja / Mannermaa, Arto / Kataja, Vesa / Kosma, Veli-Matti / Hartikainen, Jaana M / Devilee, Peter / Tollenaar, Robert A E M / Seynaeve, Caroline / Van Asperen, Christi J / Jakubowska, Anna / Lubinski, Jan / Jaworska-Bieniek, Katarzyna / Durda, Katarzyna / Slager, Susan / Toland, Amanda E / Ambrosone, Christine B / Yannoukakos, Drakoulis / Sangrajrang, Suleeporn / Gaborieau, Valerie / Brennan, Paul / McKay, James / Hamann, Ute / Torres, Diana / Zheng, Wei / Long, Jirong / Anton-Culver, Hoda / Neuhausen, Susan L / Luccarini, Craig / Baynes, Caroline / Ahmed, Shahana / Maranian, Mel / Healey, Catherine S / González-Neira, Anna / Pita, Guillermo / Alonso, M Rosario / Alvarez, Nuria / Herrero, Daniel / Tessier, Daniel C / Vincent, Daniel / Bacot, Francois / de Santiago, Ines / Carroll, Jason / Caldas, Carlos / Brown, Melissa A / Lupien, Mathieu / Kristensen, Vessela N / Pharoah, Paul D P / Chenevix-Trench, Georgia / French, Juliet D / Easton, Douglas F / Dunning, Alison M

    Nature communications

    2014  Volume 4, Page(s) 4999

    Abstract: GWAS have identified a breast cancer susceptibility locus on 2q35. Here we report the fine mapping of this locus using data from 101,943 subjects from 50 case-control studies. We genotype 276 SNPs using the 'iCOGS' genotyping array and impute genotypes ... ...

    Abstract GWAS have identified a breast cancer susceptibility locus on 2q35. Here we report the fine mapping of this locus using data from 101,943 subjects from 50 case-control studies. We genotype 276 SNPs using the 'iCOGS' genotyping array and impute genotypes for a further 1,284 using 1000 Genomes Project data. All but two, strongly correlated SNPs (rs4442975 G/T and rs6721996 G/A) are excluded as candidate causal variants at odds against >100:1. The best functional candidate, rs4442975, is associated with oestrogen receptor positive (ER+) disease with an odds ratio (OR) in Europeans of 0.85 (95% confidence interval=0.84-0.87; P=1.7 × 10(-43)) per t-allele. This SNP flanks a transcriptional enhancer that physically interacts with the promoter of IGFBP5 (encoding insulin-like growth factor-binding protein 5) and displays allele-specific gene expression, FOXA1 binding and chromatin looping. Evidence suggests that the g-allele confers increased breast cancer susceptibility through relative downregulation of IGFBP5, a gene with known roles in breast cell biology.
    MeSH term(s) Breast Neoplasms/genetics ; Breast Neoplasms/metabolism ; Cell Line, Tumor ; Chromatin/metabolism ; Chromosomes, Human, Pair 2/genetics ; Chromosomes, Human, Pair 2/metabolism ; Female ; Genetic Predisposition to Disease ; Hepatocyte Nuclear Factor 3-alpha/metabolism ; Humans ; Insulin-Like Growth Factor Binding Protein 5/genetics ; Insulin-Like Growth Factor Binding Protein 5/metabolism ; MCF-7 Cells ; Polymorphism, Single Nucleotide ; Promoter Regions, Genetic/genetics ; RNA, Messenger/metabolism
    Chemical Substances Chromatin ; FOXA1 protein, human ; Hepatocyte Nuclear Factor 3-alpha ; Insulin-Like Growth Factor Binding Protein 5 ; RNA, Messenger
    Language English
    Publishing date 2014-09-23
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/ncomms5999
    Database MEDical Literature Analysis and Retrieval System OnLINE

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