Association of PHB 1630 C>T and MTHFR 677 C>T polymorphisms with breast and ovarian cancer risk in BRCA1/2 mutation carriers: Results from a multicenter study

A. Jakubowska; D. Rozkrut; A. Antoniou; U. Hamann; R. J. Scott; L. McGuffog; S. Healy; O. M. Sinilnikova; G. Rennert; F. Lejbkowicz; A. Flugelman; I. L. Andrulis; G. Glendon; H. Ozcelik; M. Thomassen; M. Paligo; P. Aretini; J. Kantala; B. Aroer; A. Von Wachenfeldt; A. Liljegren; N. Loman; K. Herbst; U. Kristoffersson; R. Rosenquist; P. Karlsson; M. Stenmark-Askmalm; B. Melin; K. L. Nathanson; S. M. Domchek; T. Byrski; T. Huzarski; J. Gronwald; J. Menkiszak; C. Cybulski; P. Serrano; A. Osorio; T. R. Cajal; M. Tsitlaidou; J. Benítez; M. Gilbert; M. Rookus; C. M. Aalfs; I. Kluijt; J. L. Boessenkool-Pape; H. E J Meijers-Heijboer; J. C. Oosterwijk; C. J. Van Asperen; M. J. Blok; M. R. Nelen; A. M W Van Den Ouweland; C. Seynaeve; R. B. Van Der Luijt; P. Devilee; D. F. Easton; S. Peock; D. Frost; R. Platte; S. D. Ellis; E. Fineberg; D. G. Evans; F. Lalloo; R. Eeles; C. Jacobs; J. Adlard; R. Davidson; D. Eccles; T. Cole; J. Cook; A. Godwin; B. Bove; D. Stoppa-Lyonnet; V. Caux-Moncoutier; M. Belotti; C. Tirapo; S. Mazoyer; L. Barjhoux; N. Boutry-Kryza; P. Pujol; I. Coupier; J. P. Peyrat; P. Vennin; D. Muller; J. P. Fricker; L. Venat-Bouvet; O. Th Johannsson; C. Isaacs; R. Schmutzler; B. Wappenschmidt; A. Meindl; N. Arnold; R. Varon-Mateeva; D. Niederacher; C. Sutter; H. Deissler; S. Preisler-Adams; J. Simard; P. Soucy; F. Durocher; G. Chenevix-Trench; J. Beesley; X. Chen; T. Rebbeck; F. Couch; X. Wang; N. Lindor; Z. Fredericksen; V. S. Pankratz; P. Peterlongo; B. Bonanni; S. Fortuzzi; B. Peissel; C. Szabo; P. L. Mai; J. T. Loud; J. Lubinski

doi:10.1038/bjc.2012.160

Association of PHB 1630 C>T and MTHFR 677 C>T polymorphisms with breast and ovarian cancer risk in BRCA1/2 mutation carriers: Results from a multicenter study

A. Jakubowska, D. Rozkrut, A. Antoniou, U. Hamann, R. J. Scott, L. McGuffog, S. Healy, O. M. Sinilnikova, G. Rennert, F. Lejbkowicz, A. Flugelman, I. L. Andrulis, G. Glendon, H. Ozcelik, M. Thomassen, M. Paligo, P. Aretini, J. Kantala, B. Aroer, A. Von WachenfeldtA. Liljegren, N. Loman, K. Herbst, U. Kristoffersson, R. Rosenquist, P. Karlsson, M. Stenmark-Askmalm, B. Melin, K. L. Nathanson, S. M. Domchek, T. Byrski, T. Huzarski, J. Gronwald, J. Menkiszak, C. Cybulski, P. Serrano, A. Osorio, T. R. Cajal, M. Tsitlaidou, J. Benítez, M. Gilbert, M. Rookus, C. M. Aalfs, I. Kluijt, J. L. Boessenkool-Pape, H. E J Meijers-Heijboer, J. C. Oosterwijk, C. J. Van Asperen, M. J. Blok, M. R. Nelen, A. M W Van Den Ouweland, C. Seynaeve, R. B. Van Der Luijt, P. Devilee, D. F. Easton, S. Peock, D. Frost, R. Platte, S. D. Ellis, E. Fineberg, D. G. Evans, F. Lalloo, R. Eeles, C. Jacobs, J. Adlard, R. Davidson, D. Eccles, T. Cole, J. Cook, A. Godwin, B. Bove, D. Stoppa-Lyonnet, V. Caux-Moncoutier, M. Belotti, C. Tirapo, S. Mazoyer, L. Barjhoux, N. Boutry-Kryza, P. Pujol, I. Coupier, J. P. Peyrat, P. Vennin, D. Muller, J. P. Fricker, L. Venat-Bouvet, O. Th Johannsson, C. Isaacs, R. Schmutzler, B. Wappenschmidt, A. Meindl, N. Arnold, R. Varon-Mateeva, D. Niederacher, C. Sutter, H. Deissler, S. Preisler-Adams, J. Simard, P. Soucy, F. Durocher, G. Chenevix-Trench, J. Beesley, X. Chen, T. Rebbeck, F. Couch, X. Wang, N. Lindor, Z. Fredericksen, V. S. Pankratz, P. Peterlongo, B. Bonanni, S. Fortuzzi, B. Peissel, C. Szabo, P. L. Mai, J. T. Loud, J. Lubinski

Research output: Contribution to journal › Article › peer-review

Abstract

Background: The variable penetrance of breast cancer in BRCA1/2 mutation carriers suggests that other genetic or environmental factors modify breast cancer risk. Two genes of special interest are prohibitin (PHB) and methylene-tetrahydrofolate reductase (MTHFR), both of which are important either directly or indirectly in maintaining genomic integrity. Methods: To evaluate the potential role of genetic variants within PHB and MTHFR in breast and ovarian cancer risk, 4102 BRCA1 and 2093 BRCA2 mutation carriers, and 6211 BRCA1 and 2902 BRCA2 carriers from the Consortium of Investigators of Modifiers of BRCA1 and BRCA2 (CIMBA) were genotyped for the PHB 1630 C>T (rs6917) polymorphism and the MTHFR 677 C>T (rs1801133) polymorphism, respectively. Results: There was no evidence of association between the PHB 1630 C>T and MTHFR 677 C>T polymorphisms with either disease for BRCA1 or BRCA2 mutation carriers when breast and ovarian cancer associations were evaluated separately. Analysis that evaluated associations for breast and ovarian cancer simultaneously showed some evidence that BRCA1 mutation carriers who had the rare homozygote genotype (TT) of the PHB 1630 C>T polymorphism were at increased risk of both breast and ovarian cancer (HR 1.50, 95%CI 1.10-2.04 and HR 2.16, 95%CI 1.24-3.76, respectively). However, there was no evidence of association under a multiplicative model for the effect of each minor allele. Conclusion: The PHB 1630TT genotype may modify breast and ovarian cancer risks in BRCA1 mutation carriers. This association need to be evaluated in larger series of BRCA1 mutation carriers. © 2012 Cancer Research UK All rights reserved.

Original language	English
Pages (from-to)	2016-2024
Number of pages	8
Journal	British Journal of Cancer
Volume	106
Issue number	12
DOIs	https://doi.org/10.1038/bjc.2012.160
Publication status	Published - 5 Jun 2012

Keywords

BRCA1/2 mutation carriers
breast/ovarian cancer risk
MTHFR 677 C>T polymorphism
PHB 1630 C>T polymorphism

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/bjc.2012.160

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Jakubowska, A., Rozkrut, D., Antoniou, A., Hamann, U., Scott, R. J., McGuffog, L., Healy, S., Sinilnikova, O. M., Rennert, G., Lejbkowicz, F., Flugelman, A., Andrulis, I. L., Glendon, G., Ozcelik, H., Thomassen, M., Paligo, M., Aretini, P., Kantala, J., Aroer, B., ... Lubinski, J. (2012). Association of PHB 1630 C>T and MTHFR 677 C>T polymorphisms with breast and ovarian cancer risk in BRCA1/2 mutation carriers: Results from a multicenter study. British Journal of Cancer, 106(12), 2016-2024. https://doi.org/10.1038/bjc.2012.160

@article{9580b321f4874857a71e355b0e6d640d,

title = "Association of PHB 1630 C>T and MTHFR 677 C>T polymorphisms with breast and ovarian cancer risk in BRCA1/2 mutation carriers: Results from a multicenter study",

abstract = "Background: The variable penetrance of breast cancer in BRCA1/2 mutation carriers suggests that other genetic or environmental factors modify breast cancer risk. Two genes of special interest are prohibitin (PHB) and methylene-tetrahydrofolate reductase (MTHFR), both of which are important either directly or indirectly in maintaining genomic integrity. Methods: To evaluate the potential role of genetic variants within PHB and MTHFR in breast and ovarian cancer risk, 4102 BRCA1 and 2093 BRCA2 mutation carriers, and 6211 BRCA1 and 2902 BRCA2 carriers from the Consortium of Investigators of Modifiers of BRCA1 and BRCA2 (CIMBA) were genotyped for the PHB 1630 C>T (rs6917) polymorphism and the MTHFR 677 C>T (rs1801133) polymorphism, respectively. Results: There was no evidence of association between the PHB 1630 C>T and MTHFR 677 C>T polymorphisms with either disease for BRCA1 or BRCA2 mutation carriers when breast and ovarian cancer associations were evaluated separately. Analysis that evaluated associations for breast and ovarian cancer simultaneously showed some evidence that BRCA1 mutation carriers who had the rare homozygote genotype (TT) of the PHB 1630 C>T polymorphism were at increased risk of both breast and ovarian cancer (HR 1.50, 95%CI 1.10-2.04 and HR 2.16, 95%CI 1.24-3.76, respectively). However, there was no evidence of association under a multiplicative model for the effect of each minor allele. Conclusion: The PHB 1630TT genotype may modify breast and ovarian cancer risks in BRCA1 mutation carriers. This association need to be evaluated in larger series of BRCA1 mutation carriers. {\textcopyright} 2012 Cancer Research UK All rights reserved.",

keywords = "BRCA1/2 mutation carriers, breast/ovarian cancer risk, MTHFR 677 C>T polymorphism, PHB 1630 C>T polymorphism",

author = "A. Jakubowska and D. Rozkrut and A. Antoniou and U. Hamann and Scott, {R. J.} and L. McGuffog and S. Healy and Sinilnikova, {O. M.} and G. Rennert and F. Lejbkowicz and A. Flugelman and Andrulis, {I. L.} and G. Glendon and H. Ozcelik and M. Thomassen and M. Paligo and P. Aretini and J. Kantala and B. Aroer and {Von Wachenfeldt}, A. and A. Liljegren and N. Loman and K. Herbst and U. Kristoffersson and R. Rosenquist and P. Karlsson and M. Stenmark-Askmalm and B. Melin and Nathanson, {K. L.} and Domchek, {S. M.} and T. Byrski and T. Huzarski and J. Gronwald and J. Menkiszak and C. Cybulski and P. Serrano and A. Osorio and Cajal, {T. R.} and M. Tsitlaidou and J. Ben{\'i}tez and M. Gilbert and M. Rookus and Aalfs, {C. M.} and I. Kluijt and Boessenkool-Pape, {J. L.} and Meijers-Heijboer, {H. E J} and Oosterwijk, {J. C.} and {Van Asperen}, {C. J.} and Blok, {M. J.} and Nelen, {M. R.} and {Van Den Ouweland}, {A. M W} and C. Seynaeve and {Van Der Luijt}, {R. B.} and P. Devilee and Easton, {D. F.} and S. Peock and D. Frost and R. Platte and Ellis, {S. D.} and E. Fineberg and Evans, {D. G.} and F. Lalloo and R. Eeles and C. Jacobs and J. Adlard and R. Davidson and D. Eccles and T. Cole and J. Cook and A. Godwin and B. Bove and D. Stoppa-Lyonnet and V. Caux-Moncoutier and M. Belotti and C. Tirapo and S. Mazoyer and L. Barjhoux and N. Boutry-Kryza and P. Pujol and I. Coupier and Peyrat, {J. P.} and P. Vennin and D. Muller and Fricker, {J. P.} and L. Venat-Bouvet and Johannsson, {O. Th} and C. Isaacs and R. Schmutzler and B. Wappenschmidt and A. Meindl and N. Arnold and R. Varon-Mateeva and D. Niederacher and C. Sutter and H. Deissler and S. Preisler-Adams and J. Simard and P. Soucy and F. Durocher and G. Chenevix-Trench and J. Beesley and X. Chen and T. Rebbeck and F. Couch and X. Wang and N. Lindor and Z. Fredericksen and Pankratz, {V. S.} and P. Peterlongo and B. Bonanni and S. Fortuzzi and B. Peissel and C. Szabo and Mai, {P. L.} and Loud, {J. T.} and J. Lubinski",

note = "5U01CA113916, NCI NIH HHS, United StatesC1287/A10118, Cancer Research UK, United KingdomC1287/A11990, Cancer Research UK, United KingdomC5047/A8385, Cancer Research UK, United KingdomCA116201, NCI NIH HHS, United StatesP30-CA051008, NCI NIH HHS, United StatesP50 CA116201, NCI NIH HHS, United StatesR01 CA128978, NCI NIH HHS, United StatesR01 CA128978, NCI NIH HHS, United StatesR01-CA083855, NCI NIH HHS, United StatesR01-CA102776, NCI NIH HHS, United StatesRFA-CA-06-503, NCI NIH HHS, United StatesU01CA69631, NCI NIH HHS, United States, Canadian Institutes of Health Research, Canada",

year = "2012",

month = jun,

day = "5",

doi = "10.1038/bjc.2012.160",

language = "English",

volume = "106",

pages = "2016--2024",

journal = "British Journal of Cancer",

issn = "0007-0920",

publisher = "Springer Nature",

number = "12",

}

Jakubowska, A, Rozkrut, D, Antoniou, A, Hamann, U, Scott, RJ, McGuffog, L, Healy, S, Sinilnikova, OM, Rennert, G, Lejbkowicz, F, Flugelman, A, Andrulis, IL, Glendon, G, Ozcelik, H, Thomassen, M, Paligo, M, Aretini, P, Kantala, J, Aroer, B, Von Wachenfeldt, A, Liljegren, A, Loman, N, Herbst, K, Kristoffersson, U, Rosenquist, R, Karlsson, P, Stenmark-Askmalm, M, Melin, B, Nathanson, KL, Domchek, SM, Byrski, T, Huzarski, T, Gronwald, J, Menkiszak, J, Cybulski, C, Serrano, P, Osorio, A, Cajal, TR, Tsitlaidou, M, Benítez, J, Gilbert, M, Rookus, M, Aalfs, CM, Kluijt, I, Boessenkool-Pape, JL, Meijers-Heijboer, HEJ, Oosterwijk, JC, Van Asperen, CJ, Blok, MJ, Nelen, MR, Van Den Ouweland, AMW, Seynaeve, C, Van Der Luijt, RB, Devilee, P, Easton, DF, Peock, S, Frost, D, Platte, R, Ellis, SD, Fineberg, E, Evans, DG, Lalloo, F, Eeles, R, Jacobs, C, Adlard, J, Davidson, R, Eccles, D, Cole, T, Cook, J, Godwin, A, Bove, B, Stoppa-Lyonnet, D, Caux-Moncoutier, V, Belotti, M, Tirapo, C, Mazoyer, S, Barjhoux, L, Boutry-Kryza, N, Pujol, P, Coupier, I, Peyrat, JP, Vennin, P, Muller, D, Fricker, JP, Venat-Bouvet, L, Johannsson, OT, Isaacs, C, Schmutzler, R, Wappenschmidt, B, Meindl, A, Arnold, N, Varon-Mateeva, R, Niederacher, D, Sutter, C, Deissler, H, Preisler-Adams, S, Simard, J, Soucy, P, Durocher, F, Chenevix-Trench, G, Beesley, J, Chen, X, Rebbeck, T, Couch, F, Wang, X, Lindor, N, Fredericksen, Z, Pankratz, VS, Peterlongo, P, Bonanni, B, Fortuzzi, S, Peissel, B, Szabo, C, Mai, PL, Loud, JT & Lubinski, J 2012, 'Association of PHB 1630 C>T and MTHFR 677 C>T polymorphisms with breast and ovarian cancer risk in BRCA1/2 mutation carriers: Results from a multicenter study', British Journal of Cancer, vol. 106, no. 12, pp. 2016-2024. https://doi.org/10.1038/bjc.2012.160

TY - JOUR

T1 - Association of PHB 1630 C>T and MTHFR 677 C>T polymorphisms with breast and ovarian cancer risk in BRCA1/2 mutation carriers: Results from a multicenter study

AU - Jakubowska, A.

AU - Rozkrut, D.

AU - Antoniou, A.

AU - Hamann, U.

AU - Scott, R. J.

AU - McGuffog, L.

AU - Healy, S.

AU - Sinilnikova, O. M.

AU - Rennert, G.

AU - Lejbkowicz, F.

AU - Flugelman, A.

AU - Andrulis, I. L.

AU - Glendon, G.

AU - Ozcelik, H.

AU - Thomassen, M.

AU - Paligo, M.

AU - Aretini, P.

AU - Kantala, J.

AU - Aroer, B.

AU - Von Wachenfeldt, A.

AU - Liljegren, A.

AU - Loman, N.

AU - Herbst, K.

AU - Kristoffersson, U.

AU - Rosenquist, R.

AU - Karlsson, P.

AU - Stenmark-Askmalm, M.

AU - Melin, B.

AU - Nathanson, K. L.

AU - Domchek, S. M.

AU - Byrski, T.

AU - Huzarski, T.

AU - Gronwald, J.

AU - Menkiszak, J.

AU - Cybulski, C.

AU - Serrano, P.

AU - Osorio, A.

AU - Cajal, T. R.

AU - Tsitlaidou, M.

AU - Benítez, J.

AU - Gilbert, M.

AU - Rookus, M.

AU - Aalfs, C. M.

AU - Kluijt, I.

AU - Boessenkool-Pape, J. L.

AU - Meijers-Heijboer, H. E J

AU - Oosterwijk, J. C.

AU - Van Asperen, C. J.

AU - Blok, M. J.

AU - Nelen, M. R.

AU - Van Den Ouweland, A. M W

AU - Seynaeve, C.

AU - Van Der Luijt, R. B.

AU - Devilee, P.

AU - Easton, D. F.

AU - Peock, S.

AU - Frost, D.

AU - Platte, R.

AU - Ellis, S. D.

AU - Fineberg, E.

AU - Evans, D. G.

AU - Lalloo, F.

AU - Eeles, R.

AU - Jacobs, C.

AU - Adlard, J.

AU - Davidson, R.

AU - Eccles, D.

AU - Cole, T.

AU - Cook, J.

AU - Godwin, A.

AU - Bove, B.

AU - Stoppa-Lyonnet, D.

AU - Caux-Moncoutier, V.

AU - Belotti, M.

AU - Tirapo, C.

AU - Mazoyer, S.

AU - Barjhoux, L.

AU - Boutry-Kryza, N.

AU - Pujol, P.

AU - Coupier, I.

AU - Peyrat, J. P.

AU - Vennin, P.

AU - Muller, D.

AU - Fricker, J. P.

AU - Venat-Bouvet, L.

AU - Johannsson, O. Th

AU - Isaacs, C.

AU - Schmutzler, R.

AU - Wappenschmidt, B.

AU - Meindl, A.

AU - Arnold, N.

AU - Varon-Mateeva, R.

AU - Niederacher, D.

AU - Sutter, C.

AU - Deissler, H.

AU - Preisler-Adams, S.

AU - Simard, J.

AU - Soucy, P.

AU - Durocher, F.

AU - Chenevix-Trench, G.

AU - Beesley, J.

AU - Chen, X.

AU - Rebbeck, T.

AU - Couch, F.

AU - Wang, X.

AU - Lindor, N.

AU - Fredericksen, Z.

AU - Pankratz, V. S.

AU - Peterlongo, P.

AU - Bonanni, B.

AU - Fortuzzi, S.

AU - Peissel, B.

AU - Szabo, C.

AU - Mai, P. L.

AU - Loud, J. T.

AU - Lubinski, J.

N1 - 5U01CA113916, NCI NIH HHS, United StatesC1287/A10118, Cancer Research UK, United KingdomC1287/A11990, Cancer Research UK, United KingdomC5047/A8385, Cancer Research UK, United KingdomCA116201, NCI NIH HHS, United StatesP30-CA051008, NCI NIH HHS, United StatesP50 CA116201, NCI NIH HHS, United StatesR01 CA128978, NCI NIH HHS, United StatesR01 CA128978, NCI NIH HHS, United StatesR01-CA083855, NCI NIH HHS, United StatesR01-CA102776, NCI NIH HHS, United StatesRFA-CA-06-503, NCI NIH HHS, United StatesU01CA69631, NCI NIH HHS, United States, Canadian Institutes of Health Research, Canada

PY - 2012/6/5

Y1 - 2012/6/5

N2 - Background: The variable penetrance of breast cancer in BRCA1/2 mutation carriers suggests that other genetic or environmental factors modify breast cancer risk. Two genes of special interest are prohibitin (PHB) and methylene-tetrahydrofolate reductase (MTHFR), both of which are important either directly or indirectly in maintaining genomic integrity. Methods: To evaluate the potential role of genetic variants within PHB and MTHFR in breast and ovarian cancer risk, 4102 BRCA1 and 2093 BRCA2 mutation carriers, and 6211 BRCA1 and 2902 BRCA2 carriers from the Consortium of Investigators of Modifiers of BRCA1 and BRCA2 (CIMBA) were genotyped for the PHB 1630 C>T (rs6917) polymorphism and the MTHFR 677 C>T (rs1801133) polymorphism, respectively. Results: There was no evidence of association between the PHB 1630 C>T and MTHFR 677 C>T polymorphisms with either disease for BRCA1 or BRCA2 mutation carriers when breast and ovarian cancer associations were evaluated separately. Analysis that evaluated associations for breast and ovarian cancer simultaneously showed some evidence that BRCA1 mutation carriers who had the rare homozygote genotype (TT) of the PHB 1630 C>T polymorphism were at increased risk of both breast and ovarian cancer (HR 1.50, 95%CI 1.10-2.04 and HR 2.16, 95%CI 1.24-3.76, respectively). However, there was no evidence of association under a multiplicative model for the effect of each minor allele. Conclusion: The PHB 1630TT genotype may modify breast and ovarian cancer risks in BRCA1 mutation carriers. This association need to be evaluated in larger series of BRCA1 mutation carriers. © 2012 Cancer Research UK All rights reserved.

AB - Background: The variable penetrance of breast cancer in BRCA1/2 mutation carriers suggests that other genetic or environmental factors modify breast cancer risk. Two genes of special interest are prohibitin (PHB) and methylene-tetrahydrofolate reductase (MTHFR), both of which are important either directly or indirectly in maintaining genomic integrity. Methods: To evaluate the potential role of genetic variants within PHB and MTHFR in breast and ovarian cancer risk, 4102 BRCA1 and 2093 BRCA2 mutation carriers, and 6211 BRCA1 and 2902 BRCA2 carriers from the Consortium of Investigators of Modifiers of BRCA1 and BRCA2 (CIMBA) were genotyped for the PHB 1630 C>T (rs6917) polymorphism and the MTHFR 677 C>T (rs1801133) polymorphism, respectively. Results: There was no evidence of association between the PHB 1630 C>T and MTHFR 677 C>T polymorphisms with either disease for BRCA1 or BRCA2 mutation carriers when breast and ovarian cancer associations were evaluated separately. Analysis that evaluated associations for breast and ovarian cancer simultaneously showed some evidence that BRCA1 mutation carriers who had the rare homozygote genotype (TT) of the PHB 1630 C>T polymorphism were at increased risk of both breast and ovarian cancer (HR 1.50, 95%CI 1.10-2.04 and HR 2.16, 95%CI 1.24-3.76, respectively). However, there was no evidence of association under a multiplicative model for the effect of each minor allele. Conclusion: The PHB 1630TT genotype may modify breast and ovarian cancer risks in BRCA1 mutation carriers. This association need to be evaluated in larger series of BRCA1 mutation carriers. © 2012 Cancer Research UK All rights reserved.

KW - BRCA1/2 mutation carriers

KW - breast/ovarian cancer risk

KW - MTHFR 677 C>T polymorphism

KW - PHB 1630 C>T polymorphism

U2 - 10.1038/bjc.2012.160

DO - 10.1038/bjc.2012.160

M3 - Article

C2 - 22669161

SN - 0007-0920

VL - 106

SP - 2016

EP - 2024

JO - British Journal of Cancer

JF - British Journal of Cancer

IS - 12

ER -

Association of PHB 1630 C>T and MTHFR 677 C>T polymorphisms with breast and ovarian cancer risk in BRCA1/2 mutation carriers: Results from a multicenter study

Abstract

Keywords

UN SDGs

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