Interindividual variation in ovarian reserve after gonadotoxic
treatment in female childhood cancer survivors - a genome-wide
association study: results from PanCareLIFE

J 2024

Interindividual variation in ovarian reserve after gonadotoxic treatment in female childhood cancer survivors - a genome-wide association study: results from PanCareLIFE

VAN DER PERK, Madeleine M E; Linda BROER; Yutaka YASUI; Joop S E LAVEN; Leslie L ROBISON et al.

Základní údaje

Originální název

Interindividual variation in ovarian reserve after gonadotoxic treatment in female childhood cancer survivors - a genome-wide association study: results from PanCareLIFE

Autoři

Vydání

Fertility and Sterility, New York, Elsevier Science Inc. 2024, 0015-0282

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

30204 Oncology

Stát vydavatele

Spojené státy

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 7.000

Označené pro přenos do RIV

Ano

Kód RIV

RIV/00216224:14110/24:00137469

Organizační jednotka

Lékařská fakulta

Klíčová slova anglicky

Ovarian reserve; gonadotoxicity; childhood cancer; survivorship; GWAS

Štítky

14110132, 14110321, rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 30. 10. 2024 11:21, Mgr. Tereza Miškechová

Anotace

V originále

Objective To discover new variants associated with low ovarian reserve after gonadotoxic treatment among adult female childhood cancer survivors using a genome-wide association study approach. Design Genome-wide association study. Setting Not applicable. Patients A discovery cohort of adult female childhood cancer survivors from the pan-European PanCareLIFE cohort (n = 743; median age: 25.8 years), excluding those who received bilateral ovarian irradiation, bilateral oophorectomy, central nervous system or total body irradiation, or stem cell transplantation. Replication was attempted in the US-based St. Jude Lifetime Cohort (n = 391; median age: 31.3 years). Exposure Female childhood cancer survivors are at risk of therapy-related gonadal impairment. Alkylating agents are well-established risk factors, and the interindividual variability in gonadotoxicity may be explained by genetic polymorphisms. Data were collected in real-life conditions, and cyclophosphamide equivalent doses were used to quantify alkylation agent exposure. Main Outcome Measure Anti-M & uuml;llerian hormone (AMH) levels served as a proxy for ovarian function, and the findings were combined in a meta-analysis. Results Three genome-wide significant (<5.0 x 10(-8)) and 16 genome-wide suggestive (<5.0 x 10(-6)) loci were associated with log-transformed AMH levels, adjusted for cyclophosphamide equivalent dose of alkylating agents, age at diagnosis, and age at study in the PanCareLIFE cohort. On the basis of the effect allele frequency (EAF) (>0.01 if not genome-wide significant), and biologic relevance, 15 single nucleotide polymorphisms were selected for replication. None of the single nucleotide polymorphisms were statistically significantly associated with AMH levels. A meta-analysis indicated that rs78861946 was associated with borderline genome-wide statistical significance (reference/effect allele: C/T; effect allele frequency: 0.04, beta (SE): -0.484 (0.091). Conclusion This study found no genetic variants associated with a lower ovarian reserve after gonadotoxic treatment because the findings of this genome-wide association study were not statistically significant replicated in the replication cohort. Suggestive evidence for the potential importance of 1 variant is briefly discussed, but the lack of statistical significance calls for larger cohort sizes. Because the population of childhood cancer survivors is increasing, large-scale and systematic research is needed to identify genetic variants that could aid predictive risk models of gonadotoxicity as well as fertility preservation options for childhood cancer survivors.

Citovat

VAN DER PERK, Madeleine M E; Linda BROER; Yutaka YASUI; Joop S E LAVEN; Leslie L ROBISON; Wim J E TISSING; Birgitta VERSLUYS; Dorine BRESTERS; Gertjan J L KASPERS; Cornelis B LAMBALK; Annelies OVERBEEK; Jacqueline J LOONEN; Catharina C M BEERENDONK; Julianne BYRNE; Claire BERGER; Eva CLEMENS; Eline VAN DULMEN-DEN BROEDER; Uta DIRKSEN; Helena J VAN DER PAL; Andrica C H DE VRIES; Jeanette Falck WINTHER; Andreas RANFT; Sophie D FOSSA; Desiree GRABOW; Monica MURACA; Melanie KAISER; Tomáš KEPÁK; Jarmila KRUSEOVA; Dalit MODAN-MOSES; Claudia SPIX; Oliver ZOLK; Peter KAATSCH; Leontien C M KREMER; Russell J BROOKE; Fan WANG; Jessica L BAEDKE; Andre G UITTERLINDEN; Annelies M E BOS; Flora E VAN LEEUWEN; Kirsten K NESS; Melissa M HUDSON; Anne-Lotte L F VAN DER KOOI a Marry M VAN DEN HEUVEL-EIBRINK. Interindividual variation in ovarian reserve after gonadotoxic treatment in female childhood cancer survivors - a genome-wide association study: results from PanCareLIFE. Fertility and Sterility. New York: Elsevier Science Inc., 2024, roč. 122, č. 3, s. 514-524. ISSN 0015-0282. Dostupné z: https://doi.org/10.1016/j.fertnstert.2024.05.002.

@article{2447498,
   author = {van der Perk, Madeleine M E and Broer, Linda and Yasui, Yutaka and Laven, Joop S E and Robison, Leslie L and Tissing, Wim J E and Versluys, Birgitta and Bresters, Dorine and Kaspers, Gertjan J L and Lambalk, Cornelis B and Overbeek, Annelies and Loonen, Jacqueline J and Beerendonk, Catharina C M and Byrne, Julianne and Berger, Claire and Clemens, Eva and van Dulmenandden Broeder, Eline and Dirksen, Uta and van der Pal, Helena J and de Vries, Andrica C H and Winther, Jeanette Falck and Ranft, Andreas and Fossa, Sophie D and Grabow, Desiree and Muraca, Monica and Kaiser, Melanie and Kepák, Tomáš and Kruseova, Jarmila and ModanandMoses, Dalit and Spix, Claudia and Zolk, Oliver and Kaatsch, Peter and Kremer, Leontien C M and Brooke, Russell J and Wang, Fan and Baedke, Jessica L and Uitterlinden, Andre G and Bos, Annelies M E and van Leeuwen, Flora E and Ness, Kirsten K and Hudson, Melissa M and van der Kooi, AnneandLotte L F and van den HeuvelandEibrink, Marry M},
   article_location = {New York},
   article_number = {3},
   doi = {https://doi.org/10.1016/j.fertnstert.2024.05.002},
   keywords = {Ovarian reserve; gonadotoxicity; childhood cancer; survivorship; GWAS},
   language = {eng},
   issn = {0015-0282},
   journal = {Fertility and Sterility},
   title = {Interindividual variation in ovarian reserve after gonadotoxic treatment in female childhood cancer survivors - a genome-wide association study: results from PanCareLIFE},
   url = {https://www.sciencedirect.com/science/article/pii/S0015028224003121?via%3Dihub},
   volume = {122},
   year = {2024}
}

TY  - JOUR
ID  - 2447498
AU  - van der Perk, Madeleine M E - Broer, Linda - Yasui, Yutaka - Laven, Joop S E - Robison, Leslie L - Tissing, Wim J E - Versluys, Birgitta - Bresters, Dorine - Kaspers, Gertjan J L - Lambalk, Cornelis B - Overbeek, Annelies - Loonen, Jacqueline J - Beerendonk, Catharina C M - Byrne, Julianne - Berger, Claire - Clemens, Eva - van Dulmen-den Broeder, Eline - Dirksen, Uta - van der Pal, Helena J - de Vries, Andrica C H - Winther, Jeanette Falck - Ranft, Andreas - Fossa, Sophie D - Grabow, Desiree - Muraca, Monica - Kaiser, Melanie - Kepák, Tomáš - Kruseova, Jarmila - Modan-Moses, Dalit - Spix, Claudia - Zolk, Oliver - Kaatsch, Peter - Kremer, Leontien C M - Brooke, Russell J - Wang, Fan - Baedke, Jessica L - Uitterlinden, Andre G - Bos, Annelies M E - van Leeuwen, Flora E - Ness, Kirsten K - Hudson, Melissa M - van der Kooi, Anne-Lotte L F - van den Heuvel-Eibrink, Marry M
PY  - 2024
TI  - Interindividual variation in ovarian reserve after gonadotoxic treatment in female childhood cancer survivors - a genome-wide association study: results from PanCareLIFE
JF  - Fertility and Sterility
VL  - 122
IS  - 3
SP  - 514-524
EP  - 514-524
PB  - Elsevier Science Inc.
SN  - 00150282
KW  - Ovarian reserve
KW  - gonadotoxicity
KW  - childhood cancer
KW  - survivorship
KW  - GWAS
UR  - https://www.sciencedirect.com/science/article/pii/S0015028224003121?via%3Dihub
N2  - Objective To discover new variants associated with low ovarian reserve after gonadotoxic treatment among adult female childhood cancer survivors using a genome-wide association study approach. Design Genome-wide association study. Setting Not applicable. Patients A discovery cohort of adult female childhood cancer survivors from the pan-European PanCareLIFE cohort (n = 743; median age: 25.8 years), excluding those who received bilateral ovarian irradiation, bilateral oophorectomy, central nervous system or total body irradiation, or stem cell transplantation. Replication was attempted in the US-based St. Jude Lifetime Cohort (n = 391; median age: 31.3 years). Exposure Female childhood cancer survivors are at risk of therapy-related gonadal impairment. Alkylating agents are well-established risk factors, and the interindividual variability in gonadotoxicity may be explained by genetic polymorphisms. Data were collected in real-life conditions, and cyclophosphamide equivalent doses were used to quantify alkylation agent exposure. Main Outcome Measure Anti-M & uuml;llerian hormone (AMH) levels served as a proxy for ovarian function, and the findings were combined in a meta-analysis. Results Three genome-wide significant (<5.0 x 10(-8)) and 16 genome-wide suggestive (<5.0 x 10(-6)) loci were associated with log-transformed AMH levels, adjusted for cyclophosphamide equivalent dose of alkylating agents, age at diagnosis, and age at study in the PanCareLIFE cohort. On the basis of the effect allele frequency (EAF) (>0.01 if not genome-wide significant), and biologic relevance, 15 single nucleotide polymorphisms were selected for replication. None of the single nucleotide polymorphisms were statistically significantly associated with AMH levels. A meta-analysis indicated that rs78861946 was associated with borderline genome-wide statistical significance (reference/effect allele: C/T; effect allele frequency: 0.04, beta (SE): -0.484 (0.091). Conclusion This study found no genetic variants associated with a lower ovarian reserve after gonadotoxic treatment because the findings of this genome-wide association study were not statistically significant replicated in the replication cohort. Suggestive evidence for the potential importance of 1 variant is briefly discussed, but the lack of statistical significance calls for larger cohort sizes. Because the population of childhood cancer survivors is increasing, large-scale and systematic research is needed to identify genetic variants that could aid predictive risk models of gonadotoxicity as well as fertility preservation options for childhood cancer survivors.
ER  -

VAN DER PERK, Madeleine M E; Linda BROER; Yutaka YASUI; Joop S E LAVEN; Leslie L ROBISON; Wim J E TISSING; Birgitta VERSLUYS; Dorine BRESTERS; Gertjan J L KASPERS; Cornelis B LAMBALK; Annelies OVERBEEK; Jacqueline J LOONEN; Catharina C M BEERENDONK; Julianne BYRNE; Claire BERGER; Eva CLEMENS; Eline VAN DULMEN-DEN BROEDER; Uta DIRKSEN; Helena J VAN DER PAL; Andrica C H DE VRIES; Jeanette Falck WINTHER; Andreas RANFT; Sophie D FOSSA; Desiree GRABOW; Monica MURACA; Melanie KAISER; Tomáš KEPÁK; Jarmila KRUSEOVA; Dalit MODAN-MOSES; Claudia SPIX; Oliver ZOLK; Peter KAATSCH; Leontien C M KREMER; Russell J BROOKE; Fan WANG; Jessica L BAEDKE; Andre G UITTERLINDEN; Annelies M E BOS; Flora E VAN LEEUWEN; Kirsten K NESS; Melissa M HUDSON; Anne-Lotte L F VAN DER KOOI a Marry M VAN DEN HEUVEL-EIBRINK. Interindividual variation in ovarian reserve after gonadotoxic treatment in female childhood cancer survivors - a genome-wide association study: results from PanCareLIFE. \textit{Fertility and Sterility}. New York: Elsevier Science Inc., 2024, roč.~122, č.~3, s.~514-524. ISSN~0015-0282. Dostupné z: https://doi.org/10.1016/j.fertnstert.2024.05.002.

Přehled o publikaci