Polygenic Determinants for Subsequent Breast Cancer Risk in Survivors of Childhood Cancer: The St Jude Lifetime Cohort Study (SJLIFE)

Publication Date:
2018-12-15
Publisher:
The American Association for Cancer Research (AACR)
Print ISSN:
1078-0432
Electronic ISSN:
1557-3265
Topics:
Medicine
Published by:
http://www.aacr.org/
_version_ 1836399104997982209
autor Wang, Z., Liu, Q., Wilson, C. L., Easton, J., Mulder, H., Chang, T.-C., Rusch, M. C., Edmonson, M. N., Rice, S. V., Ehrhardt, M. J., Howell, R. M., Kesserwan, C. A., Wu, G., Nichols, K. E., Downing, J. R., Hudson, M. M., Zhang, J., Yasui, Y., Robison, L. L.
beschreibung Purpose: The risk of subsequent breast cancer among female childhood cancer survivors is markedly elevated. We aimed to determine genetic contributions to this risk, focusing on polygenic determinants implicated in breast cancer susceptibility in the general population. Experimental Design: Whole-genome sequencing (30 x ) was performed on survivors in the St Jude Lifetime Cohort, and germline mutations in breast cancer predisposition genes were classified for pathogenicity. A polygenic risk score (PRS) was constructed for each survivor using 170 established common risk variants. Relative rate (RR) and 95% confidence interval (95% CI) of subsequent breast cancer incidence were estimated using multivariable piecewise exponential regression. Results: The analysis included 1,133 female survivors of European ancestry (median age at last follow-up = 35.4 years; range, 8.4–67.4), of whom 47 were diagnosed with one or more subsequent breast cancers (median age at subsequent breast cancer = 40.3 years; range, 24.5–53.0). Adjusting for attained age, age at primary diagnosis, chest irradiation, doses of alkylating agents and anthracyclines, and genotype eigenvectors, RRs for survivors with PRS in the highest versus lowest quintiles were 2.7 (95% CI, 1.0–7.3), 3.0 (95% CI, 1.1–8.1), and 2.4 (95% CI, 0.1–81.1) for all survivors and survivors with and without chest irradiation, respectively. Similar associations were observed after excluding carriers of pathogenic/likely pathogenic mutations in breast cancer predisposition genes. Notably, the PRS was associated with the subsequent breast cancer rate under the age of 45 years (RR = 3.2; 95% CI, 1.2–8.3). Conclusions: Genetic profiles comprised of small-effect common variants and large-effect predisposing mutations can inform personalized breast cancer risk and surveillance/intervention in female childhood cancer survivors.
citation_standardnr 6369710
datenlieferant ipn_articles
feed_id 9363
feed_publisher The American Association for Cancer Research (AACR)
feed_publisher_url http://www.aacr.org/
insertion_date 2018-12-15
journaleissn 1557-3265
journalissn 1078-0432
publikationsjahr_anzeige 2018
publikationsjahr_facette 2018
publikationsjahr_intervall 7984:2015-2019
publikationsjahr_sort 2018
publisher The American Association for Cancer Research (AACR)
quelle Clinical Cancer Research
relation http://clincancerres.aacrjournals.org/cgi/content/short/24/24/6230?rss=1
search_space articles
shingle_author_1 Wang, Z., Liu, Q., Wilson, C. L., Easton, J., Mulder, H., Chang, T.-C., Rusch, M. C., Edmonson, M. N., Rice, S. V., Ehrhardt, M. J., Howell, R. M., Kesserwan, C. A., Wu, G., Nichols, K. E., Downing, J. R., Hudson, M. M., Zhang, J., Yasui, Y., Robison, L. L.
shingle_author_2 Wang, Z., Liu, Q., Wilson, C. L., Easton, J., Mulder, H., Chang, T.-C., Rusch, M. C., Edmonson, M. N., Rice, S. V., Ehrhardt, M. J., Howell, R. M., Kesserwan, C. A., Wu, G., Nichols, K. E., Downing, J. R., Hudson, M. M., Zhang, J., Yasui, Y., Robison, L. L.
shingle_author_3 Wang, Z., Liu, Q., Wilson, C. L., Easton, J., Mulder, H., Chang, T.-C., Rusch, M. C., Edmonson, M. N., Rice, S. V., Ehrhardt, M. J., Howell, R. M., Kesserwan, C. A., Wu, G., Nichols, K. E., Downing, J. R., Hudson, M. M., Zhang, J., Yasui, Y., Robison, L. L.
shingle_author_4 Wang, Z., Liu, Q., Wilson, C. L., Easton, J., Mulder, H., Chang, T.-C., Rusch, M. C., Edmonson, M. N., Rice, S. V., Ehrhardt, M. J., Howell, R. M., Kesserwan, C. A., Wu, G., Nichols, K. E., Downing, J. R., Hudson, M. M., Zhang, J., Yasui, Y., Robison, L. L.
shingle_catch_all_1 Polygenic Determinants for Subsequent Breast Cancer Risk in Survivors of Childhood Cancer: The St Jude Lifetime Cohort Study (SJLIFE)
Purpose: The risk of subsequent breast cancer among female childhood cancer survivors is markedly elevated. We aimed to determine genetic contributions to this risk, focusing on polygenic determinants implicated in breast cancer susceptibility in the general population. Experimental Design: Whole-genome sequencing (30 x ) was performed on survivors in the St Jude Lifetime Cohort, and germline mutations in breast cancer predisposition genes were classified for pathogenicity. A polygenic risk score (PRS) was constructed for each survivor using 170 established common risk variants. Relative rate (RR) and 95% confidence interval (95% CI) of subsequent breast cancer incidence were estimated using multivariable piecewise exponential regression. Results: The analysis included 1,133 female survivors of European ancestry (median age at last follow-up = 35.4 years; range, 8.4–67.4), of whom 47 were diagnosed with one or more subsequent breast cancers (median age at subsequent breast cancer = 40.3 years; range, 24.5–53.0). Adjusting for attained age, age at primary diagnosis, chest irradiation, doses of alkylating agents and anthracyclines, and genotype eigenvectors, RRs for survivors with PRS in the highest versus lowest quintiles were 2.7 (95% CI, 1.0–7.3), 3.0 (95% CI, 1.1–8.1), and 2.4 (95% CI, 0.1–81.1) for all survivors and survivors with and without chest irradiation, respectively. Similar associations were observed after excluding carriers of pathogenic/likely pathogenic mutations in breast cancer predisposition genes. Notably, the PRS was associated with the subsequent breast cancer rate under the age of 45 years (RR = 3.2; 95% CI, 1.2–8.3). Conclusions: Genetic profiles comprised of small-effect common variants and large-effect predisposing mutations can inform personalized breast cancer risk and surveillance/intervention in female childhood cancer survivors.
Wang, Z., Liu, Q., Wilson, C. L., Easton, J., Mulder, H., Chang, T.-C., Rusch, M. C., Edmonson, M. N., Rice, S. V., Ehrhardt, M. J., Howell, R. M., Kesserwan, C. A., Wu, G., Nichols, K. E., Downing, J. R., Hudson, M. M., Zhang, J., Yasui, Y., Robison, L. L.
The American Association for Cancer Research (AACR)
1078-0432
10780432
1557-3265
15573265
shingle_catch_all_2 Polygenic Determinants for Subsequent Breast Cancer Risk in Survivors of Childhood Cancer: The St Jude Lifetime Cohort Study (SJLIFE)
Purpose: The risk of subsequent breast cancer among female childhood cancer survivors is markedly elevated. We aimed to determine genetic contributions to this risk, focusing on polygenic determinants implicated in breast cancer susceptibility in the general population. Experimental Design: Whole-genome sequencing (30 x ) was performed on survivors in the St Jude Lifetime Cohort, and germline mutations in breast cancer predisposition genes were classified for pathogenicity. A polygenic risk score (PRS) was constructed for each survivor using 170 established common risk variants. Relative rate (RR) and 95% confidence interval (95% CI) of subsequent breast cancer incidence were estimated using multivariable piecewise exponential regression. Results: The analysis included 1,133 female survivors of European ancestry (median age at last follow-up = 35.4 years; range, 8.4–67.4), of whom 47 were diagnosed with one or more subsequent breast cancers (median age at subsequent breast cancer = 40.3 years; range, 24.5–53.0). Adjusting for attained age, age at primary diagnosis, chest irradiation, doses of alkylating agents and anthracyclines, and genotype eigenvectors, RRs for survivors with PRS in the highest versus lowest quintiles were 2.7 (95% CI, 1.0–7.3), 3.0 (95% CI, 1.1–8.1), and 2.4 (95% CI, 0.1–81.1) for all survivors and survivors with and without chest irradiation, respectively. Similar associations were observed after excluding carriers of pathogenic/likely pathogenic mutations in breast cancer predisposition genes. Notably, the PRS was associated with the subsequent breast cancer rate under the age of 45 years (RR = 3.2; 95% CI, 1.2–8.3). Conclusions: Genetic profiles comprised of small-effect common variants and large-effect predisposing mutations can inform personalized breast cancer risk and surveillance/intervention in female childhood cancer survivors.
Wang, Z., Liu, Q., Wilson, C. L., Easton, J., Mulder, H., Chang, T.-C., Rusch, M. C., Edmonson, M. N., Rice, S. V., Ehrhardt, M. J., Howell, R. M., Kesserwan, C. A., Wu, G., Nichols, K. E., Downing, J. R., Hudson, M. M., Zhang, J., Yasui, Y., Robison, L. L.
The American Association for Cancer Research (AACR)
1078-0432
10780432
1557-3265
15573265
shingle_catch_all_3 Polygenic Determinants for Subsequent Breast Cancer Risk in Survivors of Childhood Cancer: The St Jude Lifetime Cohort Study (SJLIFE)
Purpose: The risk of subsequent breast cancer among female childhood cancer survivors is markedly elevated. We aimed to determine genetic contributions to this risk, focusing on polygenic determinants implicated in breast cancer susceptibility in the general population. Experimental Design: Whole-genome sequencing (30 x ) was performed on survivors in the St Jude Lifetime Cohort, and germline mutations in breast cancer predisposition genes were classified for pathogenicity. A polygenic risk score (PRS) was constructed for each survivor using 170 established common risk variants. Relative rate (RR) and 95% confidence interval (95% CI) of subsequent breast cancer incidence were estimated using multivariable piecewise exponential regression. Results: The analysis included 1,133 female survivors of European ancestry (median age at last follow-up = 35.4 years; range, 8.4–67.4), of whom 47 were diagnosed with one or more subsequent breast cancers (median age at subsequent breast cancer = 40.3 years; range, 24.5–53.0). Adjusting for attained age, age at primary diagnosis, chest irradiation, doses of alkylating agents and anthracyclines, and genotype eigenvectors, RRs for survivors with PRS in the highest versus lowest quintiles were 2.7 (95% CI, 1.0–7.3), 3.0 (95% CI, 1.1–8.1), and 2.4 (95% CI, 0.1–81.1) for all survivors and survivors with and without chest irradiation, respectively. Similar associations were observed after excluding carriers of pathogenic/likely pathogenic mutations in breast cancer predisposition genes. Notably, the PRS was associated with the subsequent breast cancer rate under the age of 45 years (RR = 3.2; 95% CI, 1.2–8.3). Conclusions: Genetic profiles comprised of small-effect common variants and large-effect predisposing mutations can inform personalized breast cancer risk and surveillance/intervention in female childhood cancer survivors.
Wang, Z., Liu, Q., Wilson, C. L., Easton, J., Mulder, H., Chang, T.-C., Rusch, M. C., Edmonson, M. N., Rice, S. V., Ehrhardt, M. J., Howell, R. M., Kesserwan, C. A., Wu, G., Nichols, K. E., Downing, J. R., Hudson, M. M., Zhang, J., Yasui, Y., Robison, L. L.
The American Association for Cancer Research (AACR)
1078-0432
10780432
1557-3265
15573265
shingle_catch_all_4 Polygenic Determinants for Subsequent Breast Cancer Risk in Survivors of Childhood Cancer: The St Jude Lifetime Cohort Study (SJLIFE)
Purpose: The risk of subsequent breast cancer among female childhood cancer survivors is markedly elevated. We aimed to determine genetic contributions to this risk, focusing on polygenic determinants implicated in breast cancer susceptibility in the general population. Experimental Design: Whole-genome sequencing (30 x ) was performed on survivors in the St Jude Lifetime Cohort, and germline mutations in breast cancer predisposition genes were classified for pathogenicity. A polygenic risk score (PRS) was constructed for each survivor using 170 established common risk variants. Relative rate (RR) and 95% confidence interval (95% CI) of subsequent breast cancer incidence were estimated using multivariable piecewise exponential regression. Results: The analysis included 1,133 female survivors of European ancestry (median age at last follow-up = 35.4 years; range, 8.4–67.4), of whom 47 were diagnosed with one or more subsequent breast cancers (median age at subsequent breast cancer = 40.3 years; range, 24.5–53.0). Adjusting for attained age, age at primary diagnosis, chest irradiation, doses of alkylating agents and anthracyclines, and genotype eigenvectors, RRs for survivors with PRS in the highest versus lowest quintiles were 2.7 (95% CI, 1.0–7.3), 3.0 (95% CI, 1.1–8.1), and 2.4 (95% CI, 0.1–81.1) for all survivors and survivors with and without chest irradiation, respectively. Similar associations were observed after excluding carriers of pathogenic/likely pathogenic mutations in breast cancer predisposition genes. Notably, the PRS was associated with the subsequent breast cancer rate under the age of 45 years (RR = 3.2; 95% CI, 1.2–8.3). Conclusions: Genetic profiles comprised of small-effect common variants and large-effect predisposing mutations can inform personalized breast cancer risk and surveillance/intervention in female childhood cancer survivors.
Wang, Z., Liu, Q., Wilson, C. L., Easton, J., Mulder, H., Chang, T.-C., Rusch, M. C., Edmonson, M. N., Rice, S. V., Ehrhardt, M. J., Howell, R. M., Kesserwan, C. A., Wu, G., Nichols, K. E., Downing, J. R., Hudson, M. M., Zhang, J., Yasui, Y., Robison, L. L.
The American Association for Cancer Research (AACR)
1078-0432
10780432
1557-3265
15573265
shingle_title_1 Polygenic Determinants for Subsequent Breast Cancer Risk in Survivors of Childhood Cancer: The St Jude Lifetime Cohort Study (SJLIFE)
shingle_title_2 Polygenic Determinants for Subsequent Breast Cancer Risk in Survivors of Childhood Cancer: The St Jude Lifetime Cohort Study (SJLIFE)
shingle_title_3 Polygenic Determinants for Subsequent Breast Cancer Risk in Survivors of Childhood Cancer: The St Jude Lifetime Cohort Study (SJLIFE)
shingle_title_4 Polygenic Determinants for Subsequent Breast Cancer Risk in Survivors of Childhood Cancer: The St Jude Lifetime Cohort Study (SJLIFE)
timestamp 2025-06-30T23:37:40.373Z
titel Polygenic Determinants for Subsequent Breast Cancer Risk in Survivors of Childhood Cancer: The St Jude Lifetime Cohort Study (SJLIFE)
titel_suche Polygenic Determinants for Subsequent Breast Cancer Risk in Survivors of Childhood Cancer: The St Jude Lifetime Cohort Study (SJLIFE)
topic WW-YZ
uid ipn_articles_6369710