Abstract
| Original language | English |
|---|---|
| Pages (from-to) | 1653-1666 |
| Number of pages | 14 |
| Journal | Gen. Med. |
| Volume | 22 |
| Issue number | 10 |
| DOIs | |
| Publication status | Published - 2020 |
Keywords
- BRCA1/2
- breast cancer
- genetics
- ovarian cancer
- PRS
- BRCA1 protein
- BRCA2 protein
- estrogen receptor
- adult
- aged
- Article
- cancer risk
- Caucasian
- cohort analysis
- controlled study
- disease association
- estrogen receptor negative breast cancer
- estrogen receptor positive breast cancer
- female
- genetic difference
- genetic risk score
- genetic variability
- heterozygote
- human
- major clinical study
- ovary carcinoma
- pathogenicity
- population research
- prediction
- protein expression
- retrospective study
- single nucleotide polymorphism
- tumor suppressor gene
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Polygenic risk scores and breast and epithelial ovarian cancer risks for carriers of BRCA1 and BRCA2 pathogenic variants : Genetics in Medicine. / Barnes, D.R.; Rookus, M.; McGuffog, L.; Leslie, G.; Mooij, T.M.; Dennis, J.; Mavaddat, N.; Adlard, J.; Ahmed, M.; Aittomäki, K.; Andrieu, N.; Andrulis, I.L.; Arnold, N.; Arun, B.K.; Azzollini, J.; Balmaña, J.; Barkardottir, R.B.; Barrowdale, D.; Benitez, J.; Berthet, P.; Białkowska, K.; Blanco, A.M.; Blok, M.; Bonanni, B.; Boonen, S.E.; Borg, Å.; Bozsik, A.; Bradbury, A.R.; Brennan, P.; Brewer, C.; Brunet, J.; Buys, S.S.; Caldés, T.; Caligo, M.A.; Campbell, I.; Christensen, L.L.; Chung, W.K.; Claes, K.B.M.; Colas, C.; Collonge-Rame, M.-A.; Delnatte, C.; Faivre, L.; Giraud, S.; Lasset, C.; Mari, V.; Mebirouk, N.; Mouret-Fourme, E.; Schuster, H.; Stoppa-Lyonnet, D.; Antoniou, A.; Cook, J.; Davidson, R.; Easton, D.F.; Eeles, R.; Evans, D.G.; Frost, D.; Hanson, H.; Izatt, L.; Ong, K.-R.; Side, L.; O’Shaughnessy-Kirwan, A.; Tischkowitz, M.; Walker, L.; Daly, M.B.; de la Hoya, M.; de Putter, R.; Devilee, P.; Diez, O.; Ding, Y.C.; Domchek, S.M.; Dorfling, C.M.; Dumont, M.; Ejlertsen, B.; Engel, C.; Foretova, L.; Fostira, F.; Friedlander, M.; Friedman, E.; Ganz, P.A.; Garber, J.; Gehrig, A.; Gerdes, A.-M.; Gesta, P.; Glendon, G.; Godwin, A.K.; Goldgar, D.E.; González-Neira, A.; Greene, M.H.; Gschwantler-Kaulich, D.; Hahnen, E.; Hamann, U.; Hentschel, J.; Hogervorst, F.; Hooning, M.; Horvath, J.; Hu, C.; Hulick, P.J.; Imyanitov, E.N.; Chenevix-Trench, G.; Phillips, K.-A.; Spurdle, A.B.; Blok, M.; Hogervorst, F.; Hooning, M.; Koudijs, M.; Mensenkamp, A.; Meijers-Heijboer, H.; Rookus, M.; van Engelen, K.; Noguès, C.; Isaacs, C.; Izquierdo, A.; Jakubowska, A.; James, P.A.; Janavicius, R.; John, E.M.; Joseph, V.; Karlan, B.Y.; Kast, K.; Kruse, T.A.; Kwong, A.; Laitman, Y.; Lazaro, C.; Lester, J.; Lesueur, F.; Liljegren, A.; Loud, J.T.; Lubiński, J.; Mai, P.L.; Manoukian, S.; Meijers-Heijboer, H.E.J.; Meindl, A.; Mensenkamp, A.R.; Miller, A.; Montagna, M.; Mukherjee, S.; Mulligan, A.M.; Nathanson, K.L.; Neuhausen, S.L.; Nevanlinna, H.; Niederacher, D.; Nielsen, F.C.; Nikitina-Zake, L.; Olah, E.; Olopade, O.I.; Osorio, A.; Ott, C.-E.; Papi, L.; Park, S.K.; Parsons, M.T.; Pedersen, I.S.; Peissel, B.; Peixoto, A.; Peterlongo, P.; Pfeiler, G.; Prajzendanc, K.; Pujana, M.A.; Radice, P.; Ramser, J.; Ramus, S.J.; Rantala, J.; Rennert, G.; Risch, H.A.; Robson, M.; Rønlund, K.; Salani, R.; Senter, L.; Shah, P.D.; Sharma, P.; Side, L.E.; Singer, C.F.; Slavin, T.P.; Soucy, P.; Southey, M.C.; Spurdle, A.B.; Steinemann, D.; Steinsnyder, Z.; Sutter, C.; Tan, Y.Y.; Teixeira, M.R.; Teo, S.H.; Thull, D.L.; Tognazzo, S.; Toland, A.E.; Trainer, A.H.; Tung, N.; van Engelen, K.; van Rensburg, E.J.; Vega, A.; Vierstraete, J.; Wagner, G.; Wang-Gohrke, S.; Wappenschmidt, B.; Weitzel, J.N.; Yadav, S.; Yang, X.; Yannoukakos, D.; Zimbalatti, D.; Offit, K.; Thomassen, M.; Couch, F.J.; Schmutzler, R.K.; Simard, J.; Easton, D.F.; Antoniou, A.C.; Collaborators, GEMO Study; Collaborators, EMBRACE; Investigators, kConFab; Investigators, HEBON; Investigators, GENEPSO; BRCA2, on behalf of the Consortium of Investigators of Modifiers of BRCA and.
In: Gen. Med., Vol. 22, No. 10, 2020, p. 1653-1666.Research output: Contribution to journal › Article › peer-review
}
TY - JOUR
T1 - Polygenic risk scores and breast and epithelial ovarian cancer risks for carriers of BRCA1 and BRCA2 pathogenic variants
T2 - Genetics in Medicine
AU - Barnes, D.R.
AU - Rookus, M.
AU - McGuffog, L.
AU - Leslie, G.
AU - Mooij, T.M.
AU - Dennis, J.
AU - Mavaddat, N.
AU - Adlard, J.
AU - Ahmed, M.
AU - Aittomäki, K.
AU - Andrieu, N.
AU - Andrulis, I.L.
AU - Arnold, N.
AU - Arun, B.K.
AU - Azzollini, J.
AU - Balmaña, J.
AU - Barkardottir, R.B.
AU - Barrowdale, D.
AU - Benitez, J.
AU - Berthet, P.
AU - Białkowska, K.
AU - Blanco, A.M.
AU - Blok, M.
AU - Bonanni, B.
AU - Boonen, S.E.
AU - Borg, Å.
AU - Bozsik, A.
AU - Bradbury, A.R.
AU - Brennan, P.
AU - Brewer, C.
AU - Brunet, J.
AU - Buys, S.S.
AU - Caldés, T.
AU - Caligo, M.A.
AU - Campbell, I.
AU - Christensen, L.L.
AU - Chung, W.K.
AU - Claes, K.B.M.
AU - Colas, C.
AU - Collonge-Rame, M.-A.
AU - Delnatte, C.
AU - Faivre, L.
AU - Giraud, S.
AU - Lasset, C.
AU - Mari, V.
AU - Mebirouk, N.
AU - Mouret-Fourme, E.
AU - Schuster, H.
AU - Stoppa-Lyonnet, D.
AU - Antoniou, A.
AU - Cook, J.
AU - Davidson, R.
AU - Easton, D.F.
AU - Eeles, R.
AU - Evans, D.G.
AU - Frost, D.
AU - Hanson, H.
AU - Izatt, L.
AU - Ong, K.-R.
AU - Side, L.
AU - O’Shaughnessy-Kirwan, A.
AU - Tischkowitz, M.
AU - Walker, L.
AU - Daly, M.B.
AU - de la Hoya, M.
AU - de Putter, R.
AU - Devilee, P.
AU - Diez, O.
AU - Ding, Y.C.
AU - Domchek, S.M.
AU - Dorfling, C.M.
AU - Dumont, M.
AU - Ejlertsen, B.
AU - Engel, C.
AU - Foretova, L.
AU - Fostira, F.
AU - Friedlander, M.
AU - Friedman, E.
AU - Ganz, P.A.
AU - Garber, J.
AU - Gehrig, A.
AU - Gerdes, A.-M.
AU - Gesta, P.
AU - Glendon, G.
AU - Godwin, A.K.
AU - Goldgar, D.E.
AU - González-Neira, A.
AU - Greene, M.H.
AU - Gschwantler-Kaulich, D.
AU - Hahnen, E.
AU - Hamann, U.
AU - Hentschel, J.
AU - Hogervorst, F.
AU - Hooning, M.
AU - Horvath, J.
AU - Hu, C.
AU - Hulick, P.J.
AU - Imyanitov, E.N.
AU - Chenevix-Trench, G.
AU - Phillips, K.-A.
AU - Spurdle, A.B.
AU - Blok, M.
AU - Hogervorst, F.
AU - Hooning, M.
AU - Koudijs, M.
AU - Mensenkamp, A.
AU - Meijers-Heijboer, H.
AU - Rookus, M.
AU - van Engelen, K.
AU - Noguès, C.
AU - Isaacs, C.
AU - Izquierdo, A.
AU - Jakubowska, A.
AU - James, P.A.
AU - Janavicius, R.
AU - John, E.M.
AU - Joseph, V.
AU - Karlan, B.Y.
AU - Kast, K.
AU - Kruse, T.A.
AU - Kwong, A.
AU - Laitman, Y.
AU - Lazaro, C.
AU - Lester, J.
AU - Lesueur, F.
AU - Liljegren, A.
AU - Loud, J.T.
AU - Lubiński, J.
AU - Mai, P.L.
AU - Manoukian, S.
AU - Meijers-Heijboer, H.E.J.
AU - Meindl, A.
AU - Mensenkamp, A.R.
AU - Miller, A.
AU - Montagna, M.
AU - Mukherjee, S.
AU - Mulligan, A.M.
AU - Nathanson, K.L.
AU - Neuhausen, S.L.
AU - Nevanlinna, H.
AU - Niederacher, D.
AU - Nielsen, F.C.
AU - Nikitina-Zake, L.
AU - Olah, E.
AU - Olopade, O.I.
AU - Osorio, A.
AU - Ott, C.-E.
AU - Papi, L.
AU - Park, S.K.
AU - Parsons, M.T.
AU - Pedersen, I.S.
AU - Peissel, B.
AU - Peixoto, A.
AU - Peterlongo, P.
AU - Pfeiler, G.
AU - Prajzendanc, K.
AU - Pujana, M.A.
AU - Radice, P.
AU - Ramser, J.
AU - Ramus, S.J.
AU - Rantala, J.
AU - Rennert, G.
AU - Risch, H.A.
AU - Robson, M.
AU - Rønlund, K.
AU - Salani, R.
AU - Senter, L.
AU - Shah, P.D.
AU - Sharma, P.
AU - Side, L.E.
AU - Singer, C.F.
AU - Slavin, T.P.
AU - Soucy, P.
AU - Southey, M.C.
AU - Spurdle, A.B.
AU - Steinemann, D.
AU - Steinsnyder, Z.
AU - Sutter, C.
AU - Tan, Y.Y.
AU - Teixeira, M.R.
AU - Teo, S.H.
AU - Thull, D.L.
AU - Tognazzo, S.
AU - Toland, A.E.
AU - Trainer, A.H.
AU - Tung, N.
AU - van Engelen, K.
AU - van Rensburg, E.J.
AU - Vega, A.
AU - Vierstraete, J.
AU - Wagner, G.
AU - Wang-Gohrke, S.
AU - Wappenschmidt, B.
AU - Weitzel, J.N.
AU - Yadav, S.
AU - Yang, X.
AU - Yannoukakos, D.
AU - Zimbalatti, D.
AU - Offit, K.
AU - Thomassen, M.
AU - Couch, F.J.
AU - Schmutzler, R.K.
AU - Simard, J.
AU - Easton, D.F.
AU - Antoniou, A.C.
AU - Collaborators, GEMO Study
AU - Collaborators, EMBRACE
AU - Investigators, kConFab
AU - Investigators, HEBON
AU - Investigators, GENEPSO
AU - BRCA2, on behalf of the Consortium of Investigators of Modifiers of BRCA and
N1 - Cited By :2 Export Date: 1 March 2021 CODEN: GEMEF Correspondence Address: Barnes, D.R.; Centre for Cancer Genetic Epidemiology, United Kingdom; email: drb54@medschl.cam.ac.uk References: Antoniou, A., Pharoah, P.D.P., Narod, S., Average risks of breast and ovarian cancer associated with BRCA1 or BRCA2 mutations detected in case Series unselected for family history: a combined analysis of 22 studies (2003) Am J Hum Genet, 72, pp. 1117-1130. , COI: 1:CAS:528:DC%2BD3sXjslagtbg%3D; Kuchenbaecker, K.B., Hopper, J.L., Barnes, D.R., Risks of breast, ovarian, and contralateral breast cancer for BRCA1 and BRCA2 mutation carriers (2017) JAMA., 317, pp. 2402-2416. , COI: 1:CAS:528:DC%2BC2sXhtlyksr7I; Antoniou, A.C., Spurdle, A.B., Sinilnikova, O.M., Common breast cancer-predisposition alleles are associated with breast cancer risk in BRCA1 and BRCA2 mutation carriers (2008) Am J Hum Genet, 82, pp. 937-948. , COI: 1:CAS:528:DC%2BD1cXltVKrsbc%3D; Couch, F.J., Wang, X., McGuffog, L., Genome-wide association study in BRCA1 mutation carriers identifies novel loci associated with breast and ovarian cancer risk (2013) PLoS Genet., 9. , COI: 1:CAS:528:DC%2BC3sXlvValtLg%3D; Gaudet, M.M., Kuchenbaecker, K.B., Vijai, J., Identification of a BRCA2-specific modifier locus at 6p24 related to breast cancer risk (2013) PLoS Genet., 9. , COI: 1:CAS:528:DC%2BC3sXlvValtLs%3D; Milne, R.L., Kuchenbaecker, K.B., Michailidou, K., Identification of ten variants associated with risk of estrogen-receptor-negative breast cancer (2017) Nat Genet., 49, pp. 1767-1778. , COI: 1:CAS:528:DC%2BC2sXhslehtrjE; Phelan, C.M., Kuchenbaecker, K.B., Tyrer, J.P., Identification of 12 new susceptibility loci for different histotypes of epithelial ovarian cancer (2017) Nat Genet., 49, pp. 680-691. , COI: 1:CAS:528:DC%2BC2sXltVWgurs%3D; Mavaddat, N., Pharoah, P.D.P., Michailidou, K., Prediction of breast cancer risk based on profiling with common genetic variants (2015) J Natl Cancer Inst, 107, p. djv036; Yang, X., Leslie, G., Gentry-Maharaj, A., Evaluation of polygenic risk scores for ovarian cancer risk prediction in a prospective cohort study (2018) J Med Genet, 55, pp. 546-554. , COI: 1:CAS:528:DC%2BC1MXhsFSms73L; Kuchenbaecker, K.B., McGuffog, L., Barrowdale, D., Evaluation of polygenic risk scores for breast and ovarian cancer risk prediction in BRCA1 and BRCA2 mutation carriers (2017) J Natl Cancer Inst, 109, p. djw302; Michailidou, K., Lindström, S., Dennis, J., Association analysis identifies 65 new breast cancer risk loci (2017) Nature., 551, pp. 92-94; Mavaddat, N., Michailidou, K., Dennis, J., Polygenic risk scores for prediction of breast cancer and breast cancer subtypes (2019) Am J Hum Genet, 104, pp. 21-34. , COI: 1:CAS:528:DC%2BC1cXisFWqsb%2FO; Chenevix-Trench, G., Milne, R.L., Antoniou, A.C., An international initiative to identify genetic modifiers of cancer risk in BRCA1 and BRCA2 mutation carriers: the Consortium of Investigators of Modifiers of BRCA1 and BRCA2 (CIMBA) (2007) Breast Cancer Res, 9; Antoniou, A.C., Sinilnikova, O.M., Simard, J., RAD51 135G–>C modifies breast cancer risk among BRCA2 mutation carriers: results from a combined analysis of 19 studies (2007) Am J Hum Genet, 81, pp. 1186-1200. , COI: 1:CAS:528:DC%2BD2sXhtl2ju77P; Mavaddat, N., Barrowdale, D., Andrulis, I.L., Pathology of breast and ovarian cancers among BRCA1 and BRCA2 mutation carriers: results from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA) (2012) Cancer Epidemiol Biomarkers Prev, 21, pp. 134-147. , COI: 1:CAS:528:DC%2BC38XjvVWrtA%3D%3D; Lakhani, S.R., Manek, S., Penault-Llorca, F., Pathology of ovarian cancers in BRCA1 and BRCA2 carriers (2004) Clin Cancer Res, 10, pp. 2473-2481. , COI: 1:CAS:528:DC%2BD2cXivFSqsLc%3D; Antoniou, A.C., Goldgar, D.E., Andrieu, N., A weighted cohort approach for analysing factors modifying disease risks in carriers of high-risk susceptibility genes (2005) Genet Epidemiol., 29, pp. 1-11; Barnes, D.R., Lee, A., Investigators, E., kConFab, I., Easton, D.F., Antoniou, A.C., Evaluation of association methods for analysing modifiers of disease risk in carriers of high-risk mutations (2012) Genet Epidemiol., 36, pp. 274-291; Antoniou, A.C., Cunningham, A.P., Peto, J., The BOADICEA model of genetic susceptibility to breast and ovarian cancers: updates and extensions (2008) Br J Cancer, 98, pp. 1457-1466. , COI: 1:CAS:528:DC%2BD1cXks12gurw%3D; Rebbeck, T.R., Mitra, N., Wan, F., Association of type and location of BRCA1 and BRCA2 mutations with risk of breast and ovarian cancer (2015) JAMA., 313, pp. 1347-1361. , COI: 1:CAS:528:DC%2BC2MXns1SntbY%3D; Thompson, D., Easton, D., Variation in BRCA1 cancer risks by mutation position (2002) Cancer Epidemiol Biomarkers Prev, 11, pp. 329-336. , COI: 1:CAS:528:DC%2BD38XjtlCmtrw%3D, PID: 11927492; Thompson, D., Easton, D., Variation in cancer risks, by mutation position, in BRCA2 mutation carriers (2001) Am J Hum Genet, 68, pp. 410-419. , COI: 1:CAS:528:DC%2BD3MXhtl2lsLs%3D; Harrell, F.E., Evaluating the yield of medical tests (1982) JAMA, 247, pp. 2543-2546; White, I.R., Rapsomaniki, E., Covariate-adjusted measures of discrimination for survival data (2015) Biom J., 57, pp. 592-613; Antoniou, A.C., Beesley, J., McGuffog, L., Common breast cancer susceptibility alleles and the risk of breast cancer for BRCA1 and BRCA2 mutation carriers: implications for risk prediction (2010) Cancer Res., 70, pp. 9742-9754. , COI: 1:CAS:528:DC%2BC3cXhsFamurvM; Xiao, R., Boehnke, M., Quantifying and correcting for the winner’s curse in genetic association studies (2009) Genet Epidemiol., 33, pp. 453-462; Läll, K., Lepamets, M., Palover, M., Polygenic prediction of breast cancer: comparison of genetic predictors and implications for risk stratification (2019) BMC Cancer., 19; Lee, A., Mavaddat, N., Wilcox, A.N., BOADICEA: a comprehensive breast cancer risk prediction model incorporating genetic and nongenetic risk factors (2019) Genet Med, pp. 1708-1718; Mavaddat, N., Barrowdale, D., Andrulis, I.L., Pathology of breast and ovarian cancers among BRCA1 and BRCA2 mutation carriers: results from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA) (2012) Cancer Epidemiol Biomarkers Prev, 21, pp. 134-147. , COI: 1:CAS:528:DC%2BC38XjvVWrtA%3D%3D; Lee, A.J., Cunningham, A.P., Kuchenbaecker, K.B., BOADICEA breast cancer risk prediction model: updates to cancer incidences, tumour pathology and web interface (2014) Br J Cancer, 110, pp. 535-545. , COI: 1:CAS:528:DC%2BC3sXhvFCqs7vF; Antoniou, A., Anton-Culver, H., Borowsky, A., A response to “Personalised medicine and population health: breast and ovarian cancer (2019) Hum Genet., 138, pp. 287-289; (2017) IBIS Breast Cancer Risk Evaluation Tool, , http://www.ems-trials.org/riskevaluator/
PY - 2020
Y1 - 2020
N2 - Purpose: We assessed the associations between population-based polygenic risk scores (PRS) for breast (BC) or epithelial ovarian cancer (EOC) with cancer risks for BRCA1 and BRCA2 pathogenic variant carriers. Methods: Retrospective cohort data on 18,935 BRCA1 and 12,339 BRCA2 female pathogenic variant carriers of European ancestry were available. Three versions of a 313 single-nucleotide polymorphism (SNP) BC PRS were evaluated based on whether they predict overall, estrogen receptor (ER)–negative, or ER-positive BC, and two PRS for overall or high-grade serous EOC. Associations were validated in a prospective cohort. Results: The ER-negative PRS showed the strongest association with BC risk for BRCA1 carriers (hazard ratio [HR] per standard deviation = 1.29 [95% CI 1.25–1.33], P = 3×10−72). For BRCA2, the strongest association was with overall BC PRS (HR = 1.31 [95% CI 1.27–1.36], P = 7×10−50). HR estimates decreased significantly with age and there was evidence for differences in associations by predicted variant effects on protein expression. The HR estimates were smaller than general population estimates. The high-grade serous PRS yielded the strongest associations with EOC risk for BRCA1 (HR = 1.32 [95% CI 1.25–1.40], P = 3×10−22) and BRCA2 (HR = 1.44 [95% CI 1.30–1.60], P = 4×10−12) carriers. The associations in the prospective cohort were similar. Conclusion: Population-based PRS are strongly associated with BC and EOC risks for BRCA1/2 carriers and predict substantial absolute risk differences for women at PRS distribution extremes. © 2020, The Author(s).
AB - Purpose: We assessed the associations between population-based polygenic risk scores (PRS) for breast (BC) or epithelial ovarian cancer (EOC) with cancer risks for BRCA1 and BRCA2 pathogenic variant carriers. Methods: Retrospective cohort data on 18,935 BRCA1 and 12,339 BRCA2 female pathogenic variant carriers of European ancestry were available. Three versions of a 313 single-nucleotide polymorphism (SNP) BC PRS were evaluated based on whether they predict overall, estrogen receptor (ER)–negative, or ER-positive BC, and two PRS for overall or high-grade serous EOC. Associations were validated in a prospective cohort. Results: The ER-negative PRS showed the strongest association with BC risk for BRCA1 carriers (hazard ratio [HR] per standard deviation = 1.29 [95% CI 1.25–1.33], P = 3×10−72). For BRCA2, the strongest association was with overall BC PRS (HR = 1.31 [95% CI 1.27–1.36], P = 7×10−50). HR estimates decreased significantly with age and there was evidence for differences in associations by predicted variant effects on protein expression. The HR estimates were smaller than general population estimates. The high-grade serous PRS yielded the strongest associations with EOC risk for BRCA1 (HR = 1.32 [95% CI 1.25–1.40], P = 3×10−22) and BRCA2 (HR = 1.44 [95% CI 1.30–1.60], P = 4×10−12) carriers. The associations in the prospective cohort were similar. Conclusion: Population-based PRS are strongly associated with BC and EOC risks for BRCA1/2 carriers and predict substantial absolute risk differences for women at PRS distribution extremes. © 2020, The Author(s).
KW - BRCA1/2
KW - breast cancer
KW - genetics
KW - ovarian cancer
KW - PRS
KW - BRCA1 protein
KW - BRCA2 protein
KW - estrogen receptor
KW - adult
KW - aged
KW - Article
KW - cancer risk
KW - Caucasian
KW - cohort analysis
KW - controlled study
KW - disease association
KW - estrogen receptor negative breast cancer
KW - estrogen receptor positive breast cancer
KW - female
KW - genetic difference
KW - genetic risk score
KW - genetic variability
KW - heterozygote
KW - human
KW - major clinical study
KW - ovary carcinoma
KW - pathogenicity
KW - population research
KW - prediction
KW - protein expression
KW - retrospective study
KW - single nucleotide polymorphism
KW - tumor suppressor gene
U2 - 10.1038/s41436-020-0862-x
DO - 10.1038/s41436-020-0862-x
M3 - Article
VL - 22
SP - 1653
EP - 1666
JO - Gen. Med.
JF - Gen. Med.
SN - 1098-3600
IS - 10
ER -