BRCA2 Hypomorphic Missense Variants Confer Moderate Risks of Breast Cancer. Shimelis, H., Mesman, R. L. S., Von Nicolai, C., Ehlen, A., Guidugli, L., Martin, C., Calléja, F. M. G. R., Meeks, H., Hallberg, E., Hinton, J., Lilyquist, J., Hu, C., Aalfs, C. M., Aittomäki, K., Andrulis, I., Anton-Culver, H., Arndt, V., Beckmann, M. W., Benitez, J., Bogdanova, N. V., Bojesen, S. E., Bolla, M. K., Borresen-Dale, A., Brauch, H., Brennan, P., Brenner, H., Broeks, A., Brouwers, B., Brüning, T., Burwinkel, B., Chang-Claude, J., Chenevix-Trench, G., Cheng, C., Choi, J., Collée, J. M., Cox, A., Cross, S. S., Czene, K., Darabi, H., Dennis, J., Dörk, T., Dos-Santos-Silva, I., Dunning, A. M., Fasching, P. A., Figueroa, J., Flyger, H., García-Closas, M., Giles, G. G., Glendon, G., Guénel, P., Haiman, C. A., Hall, P., Hamann, U., Hartman, M., Hogervorst, F. B., Hollestelle, A., Hopper, J. L., Ito, H., Jakubowska, A., Kang, D., Kosma, V., Kristensen, V., Lai, K., Lambrechts, D., Marchand, L. L., Li, J., Lindblom, A., Lophatananon, A., Lubinski, J., Machackova, E., Mannermaa, A., Margolin, S., Marme, F., Matsuo, K., Miao, H., Michailidou, K., Milne, R. L., Muir, K., Neuhausen, S. L., Nevanlinna, H., Olson, J. E., Olswold, C., Oosterwijk, J. J. C., Osorio, A., Peterlongo, P., Peto, J., Pharoah, P. D. P., Pylkäs, K., Radice, P., Rashid, M. U., Rhenius, V., Rudolph, A., Sangrajrang, S., Sawyer, E. J., Schmidt, M. K., Schoemaker, M. J., Seynaeve, C., Shah, M., Shen, C., Shrubsole, M., Shu, X., Slager, S., Southey, M. C., Stram, D. O., Swerdlow, A., Teo, S. H., Tomlinson, I., Torres, D., Truong, T., van Asperen, C. J., van der Kolk, L. E., Wang, Q., Winqvist, R., Wu, A. H., Yu, J., Zheng, W., Zheng, Y., Leary, J., Walker, L., Foretova, L., Fostira, F., Claes, K. B. M., Varesco, L., Moghadasi, S., Easton, D. F., Spurdle, A., Devilee, P., Vrieling, H., Monteiro, A. N. A., Goldgar, D. E., Carreira, A., Vreeswijk, M. P. G., Couch, F. J., for kConFab/AOCS Investigators, & for NBCS Collaborators Cancer Research, 77(11):2789–2799, 2017. doi abstract bibtex Breast cancer risks conferred by many germline missense variants in the BRCA1 and BRCA2 genes, often referred to as variants of uncertain significance (VUS), have not been established. In this study, associations between 19 BRCA1 and 33 BRCA2 missense substitution variants and breast cancer risk were investigated through a breast cancer case-control study using genotyping data from 38 studies of predominantly European ancestry (41,890 cases and 41,607 controls) and nine studies of Asian ancestry (6,269 cases and 6,624 controls). The BRCA2 c.9104A\textgreaterC, p.Tyr3035Ser (OR = 2.52; P = 0.04), and BRCA1 c.5096G\textgreaterA, p.Arg1699Gln (OR = 4.29; P = 0.009) variant were associated with moderately increased risks of breast cancer among Europeans, whereas BRCA2 c.7522G\textgreaterA, p.Gly2508Ser (OR = 2.68; P = 0.004), and c.8187G\textgreaterT, p.Lys2729Asn (OR = 1.4; P = 0.004) were associated with moderate and low risks of breast cancer among Asians. Functional characterization of the BRCA2 variants using four quantitative assays showed reduced BRCA2 activity for p.Tyr3035Ser compared with wild-type. Overall, our results show how BRCA2 missense variants that influence protein function can confer clinically relevant, moderately increased risks of breast cancer, with potential implications for risk management guidelines in women with these specific variants. Cancer Res; 77(11); 2789-99. ©2017 AACR.
@article{shimelis_brca2_2017,
title = {{BRCA2} {Hypomorphic} {Missense} {Variants} {Confer} {Moderate} {Risks} of {Breast} {Cancer}},
volume = {77},
issn = {1538-7445},
doi = {10.1158/0008-5472.CAN-16-2568},
abstract = {Breast cancer risks conferred by many germline missense variants in the BRCA1 and BRCA2 genes, often referred to as variants of uncertain significance (VUS), have not been established. In this study, associations between 19 BRCA1 and 33 BRCA2 missense substitution variants and breast cancer risk were investigated through a breast cancer case-control study using genotyping data from 38 studies of predominantly European ancestry (41,890 cases and 41,607 controls) and nine studies of Asian ancestry (6,269 cases and 6,624 controls). The BRCA2 c.9104A{\textgreater}C, p.Tyr3035Ser (OR = 2.52; P = 0.04), and BRCA1 c.5096G{\textgreater}A, p.Arg1699Gln (OR = 4.29; P = 0.009) variant were associated with moderately increased risks of breast cancer among Europeans, whereas BRCA2 c.7522G{\textgreater}A, p.Gly2508Ser (OR = 2.68; P = 0.004), and c.8187G{\textgreater}T, p.Lys2729Asn (OR = 1.4; P = 0.004) were associated with moderate and low risks of breast cancer among Asians. Functional characterization of the BRCA2 variants using four quantitative assays showed reduced BRCA2 activity for p.Tyr3035Ser compared with wild-type. Overall, our results show how BRCA2 missense variants that influence protein function can confer clinically relevant, moderately increased risks of breast cancer, with potential implications for risk management guidelines in women with these specific variants. Cancer Res; 77(11); 2789-99. ©2017 AACR.},
language = {eng},
number = {11},
journal = {Cancer Research},
author = {Shimelis, Hermela and Mesman, Romy L. S. and Von Nicolai, Catharina and Ehlen, Asa and Guidugli, Lucia and Martin, Charlotte and Calléja, Fabienne M. G. R. and Meeks, Huong and Hallberg, Emily and Hinton, Jamie and Lilyquist, Jenna and Hu, Chunling and Aalfs, Cora M. and Aittomäki, Kristiina and Andrulis, Irene and Anton-Culver, Hoda and Arndt, Volker and Beckmann, Matthias W. and Benitez, Javier and Bogdanova, Natalia V. and Bojesen, Stig E. and Bolla, Manjeet K. and Borresen-Dale, Anne-Lise and Brauch, Hiltrud and Brennan, Paul and Brenner, Hermann and Broeks, Annegien and Brouwers, Barbara and Brüning, Thomas and Burwinkel, Barbara and Chang-Claude, Jenny and Chenevix-Trench, Georgia and Cheng, Ching-Yu and Choi, Ji-Yeob and Collée, J. Margriet and Cox, Angela and Cross, Simon S. and Czene, Kamila and Darabi, Hatef and Dennis, Joe and Dörk, Thilo and Dos-Santos-Silva, Isabel and Dunning, Alison M. and Fasching, Peter A. and Figueroa, Jonine and Flyger, Henrik and García-Closas, Montserrat and Giles, Graham G. and Glendon, Gord and Guénel, Pascal and Haiman, Christopher A. and Hall, Per and Hamann, Ute and Hartman, Mikael and Hogervorst, Frans B. and Hollestelle, Antoinette and Hopper, John L. and Ito, Hidemi and Jakubowska, Anna and Kang, Daehee and Kosma, Veli-Matti and Kristensen, Vessela and Lai, Kah-Nyin and Lambrechts, Diether and Marchand, Loic Le and Li, Jingmei and Lindblom, Annika and Lophatananon, Artitaya and Lubinski, Jan and Machackova, Eva and Mannermaa, Arto and Margolin, Sara and Marme, Frederik and Matsuo, Keitaro and Miao, Hui and Michailidou, Kyriaki and Milne, Roger L. and Muir, Kenneth and Neuhausen, Susan L. and Nevanlinna, Heli and Olson, Janet E. and Olswold, Curtis and Oosterwijk, Jan J. C. and Osorio, Ana and Peterlongo, Paolo and Peto, Julian and Pharoah, Paul D. P. and Pylkäs, Katri and Radice, Paolo and Rashid, Muhammad Usman and Rhenius, Valerie and Rudolph, Anja and Sangrajrang, Suleeporn and Sawyer, Elinor J. and Schmidt, Marjanka K. and Schoemaker, Minouk J. and Seynaeve, Caroline and Shah, Mitul and Shen, Chen-Yang and Shrubsole, Martha and Shu, Xiao-Ou and Slager, Susan and Southey, Melissa C. and Stram, Daniel O. and Swerdlow, Anthony and Teo, Soo H. and Tomlinson, Ian and Torres, Diana and Truong, Thérèse and van Asperen, Christi J. and van der Kolk, Lizet E. and Wang, Qin and Winqvist, Robert and Wu, Anna H. and Yu, Jyh-Cherng and Zheng, Wei and Zheng, Ying and Leary, Jennifer and Walker, Logan and Foretova, Lenka and Fostira, Florentia and Claes, Kathleen B. M. and Varesco, Liliana and Moghadasi, Setareh and Easton, Douglas F. and Spurdle, Amanda and Devilee, Peter and Vrieling, Harry and Monteiro, Alvaro N. A. and Goldgar, David E. and Carreira, Aura and Vreeswijk, Maaike P. G. and Couch, Fergus J. and {for kConFab/AOCS Investigators} and {for NBCS Collaborators}},
year = {2017},
pmid = {28283652},
pmcid = {PMC5508554},
keywords = {Aged, Amino Acid Substitution, Animals, BRCA2 Protein, Breast Neoplasms, Case-Control Studies, Female, Genotype, Germ-Line Mutation, Humans, Mice, Mutation, Missense, Risk},
pages = {2789--2799},
}
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{"_id":"ZhBwvH4qfxawK7Nu5","bibbaseid":"shimelis-mesman-vonnicolai-ehlen-guidugli-martin-callja-meeks-etal-brca2hypomorphicmissensevariantsconfermoderaterisksofbreastcancer-2017","author_short":["Shimelis, H.","Mesman, R. L. S.","Von Nicolai, C.","Ehlen, A.","Guidugli, L.","Martin, C.","Calléja, F. M. G. R.","Meeks, H.","Hallberg, E.","Hinton, J.","Lilyquist, J.","Hu, C.","Aalfs, C. M.","Aittomäki, K.","Andrulis, I.","Anton-Culver, H.","Arndt, V.","Beckmann, M. W.","Benitez, J.","Bogdanova, N. V.","Bojesen, S. E.","Bolla, M. K.","Borresen-Dale, A.","Brauch, H.","Brennan, P.","Brenner, H.","Broeks, A.","Brouwers, B.","Brüning, T.","Burwinkel, B.","Chang-Claude, J.","Chenevix-Trench, G.","Cheng, C.","Choi, J.","Collée, J. M.","Cox, A.","Cross, S. S.","Czene, K.","Darabi, H.","Dennis, J.","Dörk, T.","Dos-Santos-Silva, I.","Dunning, A. M.","Fasching, P. A.","Figueroa, J.","Flyger, H.","García-Closas, M.","Giles, G. G.","Glendon, G.","Guénel, P.","Haiman, C. 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In this study, associations between 19 BRCA1 and 33 BRCA2 missense substitution variants and breast cancer risk were investigated through a breast cancer case-control study using genotyping data from 38 studies of predominantly European ancestry (41,890 cases and 41,607 controls) and nine studies of Asian ancestry (6,269 cases and 6,624 controls). The BRCA2 c.9104A\\textgreaterC, p.Tyr3035Ser (OR = 2.52; P = 0.04), and BRCA1 c.5096G\\textgreaterA, p.Arg1699Gln (OR = 4.29; P = 0.009) variant were associated with moderately increased risks of breast cancer among Europeans, whereas BRCA2 c.7522G\\textgreaterA, p.Gly2508Ser (OR = 2.68; P = 0.004), and c.8187G\\textgreaterT, p.Lys2729Asn (OR = 1.4; P = 0.004) were associated with moderate and low risks of breast cancer among Asians. Functional characterization of the BRCA2 variants using four quantitative assays showed reduced BRCA2 activity for p.Tyr3035Ser compared with wild-type. 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kConFab/AOCS Investigators"],"suffixes":[]},{"firstnames":[],"propositions":[],"lastnames":["for NBCS Collaborators"],"suffixes":[]}],"year":"2017","pmid":"28283652","pmcid":"PMC5508554","keywords":"Aged, Amino Acid Substitution, Animals, BRCA2 Protein, Breast Neoplasms, Case-Control Studies, Female, Genotype, Germ-Line Mutation, Humans, Mice, Mutation, Missense, Risk","pages":"2789–2799","bibtex":"@article{shimelis_brca2_2017,\n\ttitle = {{BRCA2} {Hypomorphic} {Missense} {Variants} {Confer} {Moderate} {Risks} of {Breast} {Cancer}},\n\tvolume = {77},\n\tissn = {1538-7445},\n\tdoi = {10.1158/0008-5472.CAN-16-2568},\n\tabstract = {Breast cancer risks conferred by many germline missense variants in the BRCA1 and BRCA2 genes, often referred to as variants of uncertain significance (VUS), have not been established. In this study, associations between 19 BRCA1 and 33 BRCA2 missense substitution variants and breast cancer risk were investigated through a breast cancer case-control study using genotyping data from 38 studies of predominantly European ancestry (41,890 cases and 41,607 controls) and nine studies of Asian ancestry (6,269 cases and 6,624 controls). The BRCA2 c.9104A{\\textgreater}C, p.Tyr3035Ser (OR = 2.52; P = 0.04), and BRCA1 c.5096G{\\textgreater}A, p.Arg1699Gln (OR = 4.29; P = 0.009) variant were associated with moderately increased risks of breast cancer among Europeans, whereas BRCA2 c.7522G{\\textgreater}A, p.Gly2508Ser (OR = 2.68; P = 0.004), and c.8187G{\\textgreater}T, p.Lys2729Asn (OR = 1.4; P = 0.004) were associated with moderate and low risks of breast cancer among Asians. Functional characterization of the BRCA2 variants using four quantitative assays showed reduced BRCA2 activity for p.Tyr3035Ser compared with wild-type. Overall, our results show how BRCA2 missense variants that influence protein function can confer clinically relevant, moderately increased risks of breast cancer, with potential implications for risk management guidelines in women with these specific variants. Cancer Res; 77(11); 2789-99. ©2017 AACR.},\n\tlanguage = {eng},\n\tnumber = {11},\n\tjournal = {Cancer Research},\n\tauthor = {Shimelis, Hermela and Mesman, Romy L. S. and Von Nicolai, Catharina and Ehlen, Asa and Guidugli, Lucia and Martin, Charlotte and Calléja, Fabienne M. G. R. and Meeks, Huong and Hallberg, Emily and Hinton, Jamie and Lilyquist, Jenna and Hu, Chunling and Aalfs, Cora M. and Aittomäki, Kristiina and Andrulis, Irene and Anton-Culver, Hoda and Arndt, Volker and Beckmann, Matthias W. and Benitez, Javier and Bogdanova, Natalia V. and Bojesen, Stig E. and Bolla, Manjeet K. and Borresen-Dale, Anne-Lise and Brauch, Hiltrud and Brennan, Paul and Brenner, Hermann and Broeks, Annegien and Brouwers, Barbara and Brüning, Thomas and Burwinkel, Barbara and Chang-Claude, Jenny and Chenevix-Trench, Georgia and Cheng, Ching-Yu and Choi, Ji-Yeob and Collée, J. Margriet and Cox, Angela and Cross, Simon S. and Czene, Kamila and Darabi, Hatef and Dennis, Joe and Dörk, Thilo and Dos-Santos-Silva, Isabel and Dunning, Alison M. and Fasching, Peter A. and Figueroa, Jonine and Flyger, Henrik and García-Closas, Montserrat and Giles, Graham G. and Glendon, Gord and Guénel, Pascal and Haiman, Christopher A. and Hall, Per and Hamann, Ute and Hartman, Mikael and Hogervorst, Frans B. and Hollestelle, Antoinette and Hopper, John L. and Ito, Hidemi and Jakubowska, Anna and Kang, Daehee and Kosma, Veli-Matti and Kristensen, Vessela and Lai, Kah-Nyin and Lambrechts, Diether and Marchand, Loic Le and Li, Jingmei and Lindblom, Annika and Lophatananon, Artitaya and Lubinski, Jan and Machackova, Eva and Mannermaa, Arto and Margolin, Sara and Marme, Frederik and Matsuo, Keitaro and Miao, Hui and Michailidou, Kyriaki and Milne, Roger L. and Muir, Kenneth and Neuhausen, Susan L. and Nevanlinna, Heli and Olson, Janet E. and Olswold, Curtis and Oosterwijk, Jan J. C. and Osorio, Ana and Peterlongo, Paolo and Peto, Julian and Pharoah, Paul D. P. and Pylkäs, Katri and Radice, Paolo and Rashid, Muhammad Usman and Rhenius, Valerie and Rudolph, Anja and Sangrajrang, Suleeporn and Sawyer, Elinor J. and Schmidt, Marjanka K. and Schoemaker, Minouk J. and Seynaeve, Caroline and Shah, Mitul and Shen, Chen-Yang and Shrubsole, Martha and Shu, Xiao-Ou and Slager, Susan and Southey, Melissa C. and Stram, Daniel O. and Swerdlow, Anthony and Teo, Soo H. and Tomlinson, Ian and Torres, Diana and Truong, Thérèse and van Asperen, Christi J. and van der Kolk, Lizet E. and Wang, Qin and Winqvist, Robert and Wu, Anna H. and Yu, Jyh-Cherng and Zheng, Wei and Zheng, Ying and Leary, Jennifer and Walker, Logan and Foretova, Lenka and Fostira, Florentia and Claes, Kathleen B. M. and Varesco, Liliana and Moghadasi, Setareh and Easton, Douglas F. and Spurdle, Amanda and Devilee, Peter and Vrieling, Harry and Monteiro, Alvaro N. A. and Goldgar, David E. and Carreira, Aura and Vreeswijk, Maaike P. G. and Couch, Fergus J. and {for kConFab/AOCS Investigators} and {for NBCS Collaborators}},\n\tyear = {2017},\n\tpmid = {28283652},\n\tpmcid = {PMC5508554},\n\tkeywords = {Aged, Amino Acid Substitution, Animals, BRCA2 Protein, Breast Neoplasms, Case-Control Studies, Female, Genotype, Germ-Line Mutation, Humans, Mice, Mutation, Missense, Risk},\n\tpages = {2789--2799},\n}\n\n\n\n\n\n\n\n","author_short":["Shimelis, H.","Mesman, R. L. S.","Von Nicolai, C.","Ehlen, A.","Guidugli, L.","Martin, C.","Calléja, F. M. G. R.","Meeks, H.","Hallberg, E.","Hinton, J.","Lilyquist, J.","Hu, C.","Aalfs, C. M.","Aittomäki, K.","Andrulis, I.","Anton-Culver, H.","Arndt, V.","Beckmann, M. W.","Benitez, J.","Bogdanova, N. V.","Bojesen, S. E.","Bolla, M. K.","Borresen-Dale, A.","Brauch, H.","Brennan, P.","Brenner, H.","Broeks, A.","Brouwers, B.","Brüning, T.","Burwinkel, B.","Chang-Claude, J.","Chenevix-Trench, G.","Cheng, C.","Choi, J.","Collée, J. M.","Cox, A.","Cross, S. S.","Czene, K.","Darabi, H.","Dennis, J.","Dörk, T.","Dos-Santos-Silva, I.","Dunning, A. M.","Fasching, P. A.","Figueroa, J.","Flyger, H.","García-Closas, M.","Giles, G. G.","Glendon, G.","Guénel, P.","Haiman, C. A.","Hall, P.","Hamann, U.","Hartman, M.","Hogervorst, F. B.","Hollestelle, A.","Hopper, J. L.","Ito, H.","Jakubowska, A.","Kang, D.","Kosma, V.","Kristensen, V.","Lai, K.","Lambrechts, D.","Marchand, L. L.","Li, J.","Lindblom, A.","Lophatananon, A.","Lubinski, J.","Machackova, E.","Mannermaa, A.","Margolin, S.","Marme, F.","Matsuo, K.","Miao, H.","Michailidou, K.","Milne, R. L.","Muir, K.","Neuhausen, S. L.","Nevanlinna, H.","Olson, J. E.","Olswold, C.","Oosterwijk, J. J. C.","Osorio, A.","Peterlongo, P.","Peto, J.","Pharoah, P. D. P.","Pylkäs, K.","Radice, P.","Rashid, M. U.","Rhenius, V.","Rudolph, A.","Sangrajrang, S.","Sawyer, E. J.","Schmidt, M. K.","Schoemaker, M. J.","Seynaeve, C.","Shah, M.","Shen, C.","Shrubsole, M.","Shu, X.","Slager, S.","Southey, M. C.","Stram, D. O.","Swerdlow, A.","Teo, S. H.","Tomlinson, I.","Torres, D.","Truong, T.","van Asperen, C. J.","van der Kolk, L. E.","Wang, Q.","Winqvist, R.","Wu, A. H.","Yu, J.","Zheng, W.","Zheng, Y.","Leary, J.","Walker, L.","Foretova, L.","Fostira, F.","Claes, K. B. M.","Varesco, L.","Moghadasi, S.","Easton, D. F.","Spurdle, A.","Devilee, P.","Vrieling, H.","Monteiro, A. N. A.","Goldgar, D. E.","Carreira, A.","Vreeswijk, M. P. G.","Couch, F. J.","for kConFab/AOCS Investigators","for NBCS Collaborators"],"key":"shimelis_brca2_2017","id":"shimelis_brca2_2017","bibbaseid":"shimelis-mesman-vonnicolai-ehlen-guidugli-martin-callja-meeks-etal-brca2hypomorphicmissensevariantsconfermoderaterisksofbreastcancer-2017","role":"author","urls":{},"keyword":["Aged","Amino Acid Substitution","Animals","BRCA2 Protein","Breast Neoplasms","Case-Control Studies","Female","Genotype","Germ-Line Mutation","Humans","Mice","Mutation","Missense","Risk"],"metadata":{"authorlinks":{}},"html":""},"bibtype":"article","biburl":"https://bibbase.org/zotero-group/kyriakimi/4814086","dataSources":["NxjRpqnv6pnTsnJBJ","LvWoG6EKq8zcmdYp5"],"keywords":["aged","amino acid substitution","animals","brca2 protein","breast neoplasms","case-control studies","female","genotype","germ-line mutation","humans","mice","mutation","missense","risk"],"search_terms":["brca2","hypomorphic","missense","variants","confer","moderate","risks","breast","cancer","shimelis","mesman","von nicolai","ehlen","guidugli","martin","calléja","meeks","hallberg","hinton","lilyquist","hu","aalfs","aittomäki","andrulis","anton-culver","arndt","beckmann","benitez","bogdanova","bojesen","bolla","borresen-dale","brauch","brennan","brenner","broeks","brouwers","brüning","burwinkel","chang-claude","chenevix-trench","cheng","choi","collée","cox","cross","czene","darabi","dennis","dörk","dos-santos-silva","dunning","fasching","figueroa","flyger","garcía-closas","giles","glendon","guénel","haiman","hall","hamann","hartman","hogervorst","hollestelle","hopper","ito","jakubowska","kang","kosma","kristensen","lai","lambrechts","marchand","li","lindblom","lophatananon","lubinski","machackova","mannermaa","margolin","marme","matsuo","miao","michailidou","milne","muir","neuhausen","nevanlinna","olson","olswold","oosterwijk","osorio","peterlongo","peto","pharoah","pylkäs","radice","rashid","rhenius","rudolph","sangrajrang","sawyer","schmidt","schoemaker","seynaeve","shah","shen","shrubsole","shu","slager","southey","stram","swerdlow","teo","tomlinson","torres","truong","van asperen","van der kolk","wang","winqvist","wu","yu","zheng","zheng","leary","walker","foretova","fostira","claes","varesco","moghadasi","easton","spurdle","devilee","vrieling","monteiro","goldgar","carreira","vreeswijk","couch","for kconfab/aocs investigators","for nbcs collaborators"],"title":"BRCA2 Hypomorphic Missense Variants Confer Moderate Risks of Breast Cancer","year":2017}