Identification of 22 susceptibility loci associated with testicular germ cell tumors

Testicular Canc Consortium; John Pluta; Louise C. Pyle; Kevin T. Nead; Rona Wilf; Mingyao Li; Nandita Mitra; Benita Weathers; Kurt D'Andrea; Kristian Almstrup; Lynn Anson-Cartwright; Javier Benitez; Christopher D. Brown; Stephen Chanock; Chu Chen; Victoria K. Cortessis; Alberto Ferlin; Carlo Foresta; Marija Gamulin; Jourik A. Gietema; Chiara Grasso; Mark H. Greene; Tom Grotmol; Robert J. Hamilton; Trine B. Haugen; Russ Hauser; Michelle A. T. Hildebrandt; Matthew E. Johnson; Robert Karlsson; Lambertus A. Kiemeney; Davor Lessel; Ragnhild A. Lothe; Jennifer T. Loud; Chey Loveday; Paloma Martin-Gimeno; Coby Meijer; Jeremie Nsengimana; David I. Quinn; Thorunn Rafnar; Shweta Ramdas; Lorenzo Richiardi; Rolf I. Skotheim; Kari Stefansson; Clare Turnbull; David J. Vaughn; Fredrik Wiklund; Xifeng Wu; Daphne Yang; Tongzhang Zheng; Andrew D. Wells; Struan F. A. Grant

doi:10.1038/s41467-021-24334-y

Identification of 22 susceptibility loci associated with testicular germ cell tumors

Testicular Canc Consortium, John Pluta, Louise C. Pyle, Kevin T. Nead, Rona Wilf, Mingyao Li, Nandita Mitra, Benita Weathers, Kurt D'Andrea, Kristian Almstrup, Lynn Anson-Cartwright, Javier Benitez, Christopher D. Brown, Stephen Chanock, Chu Chen, Victoria K. Cortessis, Alberto Ferlin, Carlo Foresta, Marija Gamulin, Jourik A. GietemaChiara Grasso, Mark H. Greene, Tom Grotmol, Robert J. Hamilton, Trine B. Haugen, Russ Hauser, Michelle A. T. Hildebrandt, Matthew E. Johnson, Robert Karlsson, Lambertus A. Kiemeney, Davor Lessel, Ragnhild A. Lothe, Jennifer T. Loud, Chey Loveday, Paloma Martin-Gimeno, Coby Meijer, Jeremie Nsengimana, David I. Quinn, Thorunn Rafnar, Shweta Ramdas, Lorenzo Richiardi, Rolf I. Skotheim, Kari Stefansson, Clare Turnbull, David J. Vaughn, Fredrik Wiklund, Xifeng Wu, Daphne Yang, Tongzhang Zheng, Andrew D. Wells, Struan F. A. Grant

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Testicular germ cell tumors (TGCT) are the most common tumor in young white men and have a high heritability. In this study, the international Testicular Cancer Consortium assemble 10,156 and 179,683 men with and without TGCT, respectively, for a genome-wide association study. This meta-analysis identifies 22 TGCT susceptibility loci, bringing the total to 78, which account for 44% of disease heritability. Men with a polygenic risk score (PRS) in the 95(th) percentile have a 6.8-fold increased risk of TGCT compared to men with median scores. Among men with independent TGCT risk factors such as cryptorchidism, the PRS may guide screening decisions with the goal of reducing treatment-related complications causing long-term morbidity in survivors. These findings emphasize the interconnected nature of two known pathways that promote TGCT susceptibility: male germ cell development within its somatic niche and regulation of chromosomal division and structure, and implicate an additional biological pathway, mRNA translation. Testicular germ cell tumors are highly heritable, and the authors present the largest genome association study, identifying 22 novel loci, which account for a third of those identified to date. Implicated pathways include male germ cell development and differentiation, and chromosomal segregation.

Originele taal-2	English
Artikelnummer	4487
Aantal pagina's	13
Tijdschrift	Nature Communications
Volume	12
Nummer van het tijdschrift	1
DOI's	https://doi.org/10.1038/s41467-021-24334-y
Status	Published - 23-jul.-2021

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Testicular Canc Consortium, Pluta, J., Pyle, L. C., Nead, K. T., Wilf, R., Li, M., Mitra, N., Weathers, B., D'Andrea, K., Almstrup, K., Anson-Cartwright, L., Benitez, J., Brown, C. D., Chanock, S., Chen, C., Cortessis, V. K., Ferlin, A., Foresta, C., Gamulin, M., ... Grant, S. F. A. (2021). Identification of 22 susceptibility loci associated with testicular germ cell tumors. Nature Communications, 12(1), Artikel 4487. https://doi.org/10.1038/s41467-021-24334-y

@article{8fd85cfa0cdf4e4ea202df7752fddb51,

title = "Identification of 22 susceptibility loci associated with testicular germ cell tumors",

abstract = "Testicular germ cell tumors (TGCT) are the most common tumor in young white men and have a high heritability. In this study, the international Testicular Cancer Consortium assemble 10,156 and 179,683 men with and without TGCT, respectively, for a genome-wide association study. This meta-analysis identifies 22 TGCT susceptibility loci, bringing the total to 78, which account for 44% of disease heritability. Men with a polygenic risk score (PRS) in the 95(th) percentile have a 6.8-fold increased risk of TGCT compared to men with median scores. Among men with independent TGCT risk factors such as cryptorchidism, the PRS may guide screening decisions with the goal of reducing treatment-related complications causing long-term morbidity in survivors. These findings emphasize the interconnected nature of two known pathways that promote TGCT susceptibility: male germ cell development within its somatic niche and regulation of chromosomal division and structure, and implicate an additional biological pathway, mRNA translation. Testicular germ cell tumors are highly heritable, and the authors present the largest genome association study, identifying 22 novel loci, which account for a third of those identified to date. Implicated pathways include male germ cell development and differentiation, and chromosomal segregation.",

keywords = "GENOME-WIDE ASSOCIATION, GENOTYPE IMPUTATION, FAMILIAL RISK, CENP-I, CANCER, VARIANTS, BAX, DMRT1, METAANALYSIS, SINGLE",

author = "{Testicular Canc Consortium} and John Pluta and Pyle, {Louise C.} and Nead, {Kevin T.} and Rona Wilf and Mingyao Li and Nandita Mitra and Benita Weathers and Kurt D'Andrea and Kristian Almstrup and Lynn Anson-Cartwright and Javier Benitez and Brown, {Christopher D.} and Stephen Chanock and Chu Chen and Cortessis, {Victoria K.} and Alberto Ferlin and Carlo Foresta and Marija Gamulin and Gietema, {Jourik A.} and Chiara Grasso and Greene, {Mark H.} and Tom Grotmol and Hamilton, {Robert J.} and Haugen, {Trine B.} and Russ Hauser and Hildebrandt, {Michelle A. T.} and Johnson, {Matthew E.} and Robert Karlsson and Kiemeney, {Lambertus A.} and Davor Lessel and Lothe, {Ragnhild A.} and Loud, {Jennifer T.} and Chey Loveday and Paloma Martin-Gimeno and Coby Meijer and Jeremie Nsengimana and Quinn, {David I.} and Thorunn Rafnar and Shweta Ramdas and Lorenzo Richiardi and Skotheim, {Rolf I.} and Kari Stefansson and Clare Turnbull and Vaughn, {David J.} and Fredrik Wiklund and Xifeng Wu and Daphne Yang and Tongzhang Zheng and Wells, {Andrew D.} and Grant, {Struan F. A.}",

note = "{\textcopyright} 2021. The Author(s).",

year = "2021",

month = jul,

day = "23",

doi = "10.1038/s41467-021-24334-y",

language = "English",

volume = "12",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "Nature Publishing Group",

number = "1",

}

Testicular Canc Consortium, Pluta, J, Pyle, LC, Nead, KT, Wilf, R, Li, M, Mitra, N, Weathers, B, D'Andrea, K, Almstrup, K, Anson-Cartwright, L, Benitez, J, Brown, CD, Chanock, S, Chen, C, Cortessis, VK, Ferlin, A, Foresta, C, Gamulin, M, Gietema, JA, Grasso, C, Greene, MH, Grotmol, T, Hamilton, RJ, Haugen, TB, Hauser, R, Hildebrandt, MAT, Johnson, ME, Karlsson, R, Kiemeney, LA, Lessel, D, Lothe, RA, Loud, JT, Loveday, C, Martin-Gimeno, P, Meijer, C, Nsengimana, J, Quinn, DI, Rafnar, T, Ramdas, S, Richiardi, L, Skotheim, RI, Stefansson, K, Turnbull, C, Vaughn, DJ, Wiklund, F, Wu, X, Yang, D, Zheng, T, Wells, AD & Grant, SFA 2021, 'Identification of 22 susceptibility loci associated with testicular germ cell tumors', Nature Communications, vol. 12, nr. 1, 4487. https://doi.org/10.1038/s41467-021-24334-y

TY - JOUR

T1 - Identification of 22 susceptibility loci associated with testicular germ cell tumors

AU - Testicular Canc Consortium

AU - Pluta, John

AU - Pyle, Louise C.

AU - Nead, Kevin T.

AU - Wilf, Rona

AU - Li, Mingyao

AU - Mitra, Nandita

AU - Weathers, Benita

AU - D'Andrea, Kurt

AU - Almstrup, Kristian

AU - Anson-Cartwright, Lynn

AU - Benitez, Javier

AU - Brown, Christopher D.

AU - Chanock, Stephen

AU - Chen, Chu

AU - Cortessis, Victoria K.

AU - Ferlin, Alberto

AU - Foresta, Carlo

AU - Gamulin, Marija

AU - Gietema, Jourik A.

AU - Grasso, Chiara

AU - Greene, Mark H.

AU - Grotmol, Tom

AU - Hamilton, Robert J.

AU - Haugen, Trine B.

AU - Hauser, Russ

AU - Hildebrandt, Michelle A. T.

AU - Johnson, Matthew E.

AU - Karlsson, Robert

AU - Kiemeney, Lambertus A.

AU - Lessel, Davor

AU - Lothe, Ragnhild A.

AU - Loud, Jennifer T.

AU - Loveday, Chey

AU - Martin-Gimeno, Paloma

AU - Meijer, Coby

AU - Nsengimana, Jeremie

AU - Quinn, David I.

AU - Rafnar, Thorunn

AU - Ramdas, Shweta

AU - Richiardi, Lorenzo

AU - Skotheim, Rolf I.

AU - Stefansson, Kari

AU - Turnbull, Clare

AU - Vaughn, David J.

AU - Wiklund, Fredrik

AU - Wu, Xifeng

AU - Yang, Daphne

AU - Zheng, Tongzhang

AU - Wells, Andrew D.

AU - Grant, Struan F. A.

PY - 2021/7/23

Y1 - 2021/7/23

N2 - Testicular germ cell tumors (TGCT) are the most common tumor in young white men and have a high heritability. In this study, the international Testicular Cancer Consortium assemble 10,156 and 179,683 men with and without TGCT, respectively, for a genome-wide association study. This meta-analysis identifies 22 TGCT susceptibility loci, bringing the total to 78, which account for 44% of disease heritability. Men with a polygenic risk score (PRS) in the 95(th) percentile have a 6.8-fold increased risk of TGCT compared to men with median scores. Among men with independent TGCT risk factors such as cryptorchidism, the PRS may guide screening decisions with the goal of reducing treatment-related complications causing long-term morbidity in survivors. These findings emphasize the interconnected nature of two known pathways that promote TGCT susceptibility: male germ cell development within its somatic niche and regulation of chromosomal division and structure, and implicate an additional biological pathway, mRNA translation. Testicular germ cell tumors are highly heritable, and the authors present the largest genome association study, identifying 22 novel loci, which account for a third of those identified to date. Implicated pathways include male germ cell development and differentiation, and chromosomal segregation.

AB - Testicular germ cell tumors (TGCT) are the most common tumor in young white men and have a high heritability. In this study, the international Testicular Cancer Consortium assemble 10,156 and 179,683 men with and without TGCT, respectively, for a genome-wide association study. This meta-analysis identifies 22 TGCT susceptibility loci, bringing the total to 78, which account for 44% of disease heritability. Men with a polygenic risk score (PRS) in the 95(th) percentile have a 6.8-fold increased risk of TGCT compared to men with median scores. Among men with independent TGCT risk factors such as cryptorchidism, the PRS may guide screening decisions with the goal of reducing treatment-related complications causing long-term morbidity in survivors. These findings emphasize the interconnected nature of two known pathways that promote TGCT susceptibility: male germ cell development within its somatic niche and regulation of chromosomal division and structure, and implicate an additional biological pathway, mRNA translation. Testicular germ cell tumors are highly heritable, and the authors present the largest genome association study, identifying 22 novel loci, which account for a third of those identified to date. Implicated pathways include male germ cell development and differentiation, and chromosomal segregation.

KW - GENOME-WIDE ASSOCIATION

KW - GENOTYPE IMPUTATION

KW - FAMILIAL RISK

KW - CENP-I

KW - CANCER

KW - VARIANTS

KW - BAX

KW - DMRT1

KW - METAANALYSIS

KW - SINGLE

U2 - 10.1038/s41467-021-24334-y

DO - 10.1038/s41467-021-24334-y

M3 - Article

C2 - 34301922

SN - 2041-1723

VL - 12

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 4487

ER -

Identification of 22 susceptibility loci associated with testicular germ cell tumors

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