Variants in activators and downstream targets of ATM, radiation exposure, and contralateral breast cancer risk in the WECARE study

Jennifer D. Brooks; Sharon N. Teraoka; Anne S. Reiner; Jaya M. Satagopan; Leslie Bernstein; Duncan C. Thomas; Marinela Capanu; Marilyn Stovall; Susan A. Smith; Shan Wei; Roy E. Shore; John D. Boice; Charles F. Lynch; Lene Mellemkjær; Kathleen E. Malone; Xiaolin Liang; Robert W. Haile; Patrick Concannon; Jonine L. Bernstein; Colin Begg; Irene Orlow; Robert Klein; Ken Offit; Meghan Woods; Esther M. John; Wei Wang; Jørgen H. Olsen; Noemi Epstein; Daniela Seminara; Julia Knight; Anna Chiarelli; David Duggan; Jeanne DeWall; Daniel Stram; Anh T. Diep; Shanyan Xue; Nianmin Zhou; Evgenia Ter-Karapetova; Susan Smith; Sharon Teraoka; Eric R. Olson; V. Anne Morrison; Lemuel Navarro; Karen M. Cerosaletti; Jocyndra Wright

doi:10.1002/humu.21604

Variants in activators and downstream targets of ATM, radiation exposure, and contralateral breast cancer risk in the WECARE study

Jennifer D. Brooks, Sharon N. Teraoka, Anne S. Reiner, Jaya M. Satagopan, Leslie Bernstein, Duncan C. Thomas, Marinela Capanu, Marilyn Stovall, Susan A. Smith, Shan Wei, Roy E. Shore, John D. Boice, Charles F. Lynch, Lene Mellemkjær, Kathleen E. Malone, Xiaolin Liang, Robert W. Haile, Patrick Concannon, Jonine L. Bernstein, Colin BeggIrene Orlow, Robert Klein, Ken Offit, Meghan Woods, Esther M. John, Wei Wang, Jørgen H. Olsen, Noemi Epstein, Daniela Seminara, Julia Knight, Anna Chiarelli, David Duggan, Jeanne DeWall, Daniel Stram, Anh T. Diep, Shanyan Xue, Nianmin Zhou, Evgenia Ter-Karapetova, Susan Smith, Sharon Teraoka, Eric R. Olson, V. Anne Morrison, Lemuel Navarro, Karen M. Cerosaletti, Jocyndra Wright

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

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Abstract

Ionizing radiation (IR) is a breast carcinogen that induces DNA double-strand breaks (DSBs), and variation in genes involved in the DNA DSB response has been implicated in radiation-induced breast cancer. The Women's Environmental, Cancer, and Radiation Epidemiology (WECARE) study is a populationbased study of cases with contralateral breast cancer (CBC) and matched controls with unilateral breast cancer. The location-specific radiation dose received by the contralateral breast was estimated from radiotherapy records and mathematical models. One hundred fifty-two SNPs in six genes (CHEK2, MRE11A, MDC1, NBN, RAD50, TP53BP1) involved in the DNA DSBs response were genotyped. No variants or haplotypes were associated with CBC risk (649 cases and 1,284 controls) and no variants were found to interact with radiation dose. Carriers of a RAD50 haplotype exposed to ≥1 gray (Gy) had an increased risk of CBC compared with unexposed carriers (Rate ratios [RR] = 4.31 [95% confidence intervals [CI] 1.93-9.62]); with an excess relative risk (ERR) per Gy = 2.13 [95% CI 0.61-5.33]). Although the results of this study were largely null, carriers of a haplotype in RAD50 treated with radiation had a greater CBC risk than unexposed carriers. This suggests that carriers of this haplotype may be susceptible to the DNA-damaging effects of radiation therapy associated with radiationinduced breast cancer.

Original language	English
Pages (from-to)	158-164
Number of pages	7
Journal	Human Mutation
Volume	33
Issue number	1
DOIs	https://doi.org/10.1002/humu.21604
State	Published - Jan 2012
Externally published	Yes

Keywords

Contralateral breast cancer
DNA repair
Haplotypes
Polymorphisms
Radiation

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Brooks, J. D., Teraoka, S. N., Reiner, A. S., Satagopan, J. M., Bernstein, L., Thomas, D. C., Capanu, M., Stovall, M., Smith, S. A., Wei, S., Shore, R. E., Boice, J. D., Lynch, C. F., Mellemkjær, L., Malone, K. E., Liang, X., Haile, R. W., Concannon, P., Bernstein, J. L., ... Wright, J. (2012). Variants in activators and downstream targets of ATM, radiation exposure, and contralateral breast cancer risk in the WECARE study. Human Mutation, 33(1), 158-164. https://doi.org/10.1002/humu.21604

@article{c5035f3f6a31498193b95da5ff71c62b,

title = "Variants in activators and downstream targets of ATM, radiation exposure, and contralateral breast cancer risk in the WECARE study",

abstract = "Ionizing radiation (IR) is a breast carcinogen that induces DNA double-strand breaks (DSBs), and variation in genes involved in the DNA DSB response has been implicated in radiation-induced breast cancer. The Women's Environmental, Cancer, and Radiation Epidemiology (WECARE) study is a populationbased study of cases with contralateral breast cancer (CBC) and matched controls with unilateral breast cancer. The location-specific radiation dose received by the contralateral breast was estimated from radiotherapy records and mathematical models. One hundred fifty-two SNPs in six genes (CHEK2, MRE11A, MDC1, NBN, RAD50, TP53BP1) involved in the DNA DSBs response were genotyped. No variants or haplotypes were associated with CBC risk (649 cases and 1,284 controls) and no variants were found to interact with radiation dose. Carriers of a RAD50 haplotype exposed to ≥1 gray (Gy) had an increased risk of CBC compared with unexposed carriers (Rate ratios [RR] = 4.31 [95% confidence intervals [CI] 1.93-9.62]); with an excess relative risk (ERR) per Gy = 2.13 [95% CI 0.61-5.33]). Although the results of this study were largely null, carriers of a haplotype in RAD50 treated with radiation had a greater CBC risk than unexposed carriers. This suggests that carriers of this haplotype may be susceptible to the DNA-damaging effects of radiation therapy associated with radiationinduced breast cancer.",

keywords = "Contralateral breast cancer, DNA repair, Haplotypes, Polymorphisms, Radiation",

author = "Brooks, {Jennifer D.} and Teraoka, {Sharon N.} and Reiner, {Anne S.} and Satagopan, {Jaya M.} and Leslie Bernstein and Thomas, {Duncan C.} and Marinela Capanu and Marilyn Stovall and Smith, {Susan A.} and Shan Wei and Shore, {Roy E.} and Boice, {John D.} and Lynch, {Charles F.} and Lene Mellemkj{\ae}r and Malone, {Kathleen E.} and Xiaolin Liang and Haile, {Robert W.} and Patrick Concannon and Bernstein, {Jonine L.} and Colin Begg and Irene Orlow and Robert Klein and Ken Offit and Meghan Woods and John, {Esther M.} and Wei Wang and Olsen, {J{\o}rgen H.} and Noemi Epstein and Daniela Seminara and Julia Knight and Anna Chiarelli and David Duggan and Jeanne DeWall and Daniel Stram and Diep, {Anh T.} and Shanyan Xue and Nianmin Zhou and Evgenia Ter-Karapetova and Susan Smith and Sharon Teraoka and Olson, {Eric R.} and Morrison, {V. Anne} and Lemuel Navarro and Cerosaletti, {Karen M.} and Jocyndra Wright",

year = "2012",

month = jan,

doi = "10.1002/humu.21604",

language = "English",

volume = "33",

pages = "158--164",

journal = "Human Mutation",

issn = "1059-7794",

publisher = "Wiley-Liss Inc.",

number = "1",

}

Brooks, JD, Teraoka, SN, Reiner, AS, Satagopan, JM, Bernstein, L, Thomas, DC, Capanu, M, Stovall, M, Smith, SA, Wei, S, Shore, RE, Boice, JD, Lynch, CF, Mellemkjær, L, Malone, KE, Liang, X, Haile, RW, Concannon, P, Bernstein, JL, Begg, C, Orlow, I, Klein, R, Offit, K, Woods, M, John, EM, Wang, W, Olsen, JH, Epstein, N, Seminara, D, Knight, J, Chiarelli, A, Duggan, D, DeWall, J, Stram, D, Diep, AT, Xue, S, Zhou, N, Ter-Karapetova, E, Smith, S, Teraoka, S, Olson, ER, Morrison, VA, Navarro, L, Cerosaletti, KM & Wright, J 2012, 'Variants in activators and downstream targets of ATM, radiation exposure, and contralateral breast cancer risk in the WECARE study', Human Mutation, vol. 33, no. 1, pp. 158-164. https://doi.org/10.1002/humu.21604

TY - JOUR

T1 - Variants in activators and downstream targets of ATM, radiation exposure, and contralateral breast cancer risk in the WECARE study

AU - Brooks, Jennifer D.

AU - Teraoka, Sharon N.

AU - Reiner, Anne S.

AU - Satagopan, Jaya M.

AU - Bernstein, Leslie

AU - Thomas, Duncan C.

AU - Capanu, Marinela

AU - Stovall, Marilyn

AU - Smith, Susan A.

AU - Wei, Shan

AU - Shore, Roy E.

AU - Boice, John D.

AU - Lynch, Charles F.

AU - Mellemkjær, Lene

AU - Malone, Kathleen E.

AU - Liang, Xiaolin

AU - Haile, Robert W.

AU - Concannon, Patrick

AU - Bernstein, Jonine L.

AU - Begg, Colin

AU - Orlow, Irene

AU - Klein, Robert

AU - Offit, Ken

AU - Woods, Meghan

AU - John, Esther M.

AU - Wang, Wei

AU - Olsen, Jørgen H.

AU - Epstein, Noemi

AU - Seminara, Daniela

AU - Knight, Julia

AU - Chiarelli, Anna

AU - Duggan, David

AU - DeWall, Jeanne

AU - Stram, Daniel

AU - Diep, Anh T.

AU - Xue, Shanyan

AU - Zhou, Nianmin

AU - Ter-Karapetova, Evgenia

AU - Smith, Susan

AU - Teraoka, Sharon

AU - Olson, Eric R.

AU - Morrison, V. Anne

AU - Navarro, Lemuel

AU - Cerosaletti, Karen M.

AU - Wright, Jocyndra

PY - 2012/1

Y1 - 2012/1

N2 - Ionizing radiation (IR) is a breast carcinogen that induces DNA double-strand breaks (DSBs), and variation in genes involved in the DNA DSB response has been implicated in radiation-induced breast cancer. The Women's Environmental, Cancer, and Radiation Epidemiology (WECARE) study is a populationbased study of cases with contralateral breast cancer (CBC) and matched controls with unilateral breast cancer. The location-specific radiation dose received by the contralateral breast was estimated from radiotherapy records and mathematical models. One hundred fifty-two SNPs in six genes (CHEK2, MRE11A, MDC1, NBN, RAD50, TP53BP1) involved in the DNA DSBs response were genotyped. No variants or haplotypes were associated with CBC risk (649 cases and 1,284 controls) and no variants were found to interact with radiation dose. Carriers of a RAD50 haplotype exposed to ≥1 gray (Gy) had an increased risk of CBC compared with unexposed carriers (Rate ratios [RR] = 4.31 [95% confidence intervals [CI] 1.93-9.62]); with an excess relative risk (ERR) per Gy = 2.13 [95% CI 0.61-5.33]). Although the results of this study were largely null, carriers of a haplotype in RAD50 treated with radiation had a greater CBC risk than unexposed carriers. This suggests that carriers of this haplotype may be susceptible to the DNA-damaging effects of radiation therapy associated with radiationinduced breast cancer.

AB - Ionizing radiation (IR) is a breast carcinogen that induces DNA double-strand breaks (DSBs), and variation in genes involved in the DNA DSB response has been implicated in radiation-induced breast cancer. The Women's Environmental, Cancer, and Radiation Epidemiology (WECARE) study is a populationbased study of cases with contralateral breast cancer (CBC) and matched controls with unilateral breast cancer. The location-specific radiation dose received by the contralateral breast was estimated from radiotherapy records and mathematical models. One hundred fifty-two SNPs in six genes (CHEK2, MRE11A, MDC1, NBN, RAD50, TP53BP1) involved in the DNA DSBs response were genotyped. No variants or haplotypes were associated with CBC risk (649 cases and 1,284 controls) and no variants were found to interact with radiation dose. Carriers of a RAD50 haplotype exposed to ≥1 gray (Gy) had an increased risk of CBC compared with unexposed carriers (Rate ratios [RR] = 4.31 [95% confidence intervals [CI] 1.93-9.62]); with an excess relative risk (ERR) per Gy = 2.13 [95% CI 0.61-5.33]). Although the results of this study were largely null, carriers of a haplotype in RAD50 treated with radiation had a greater CBC risk than unexposed carriers. This suggests that carriers of this haplotype may be susceptible to the DNA-damaging effects of radiation therapy associated with radiationinduced breast cancer.

KW - Contralateral breast cancer

KW - DNA repair

KW - Haplotypes

KW - Polymorphisms

KW - Radiation

UR - http://www.scopus.com/inward/record.url?scp=84863283896&partnerID=8YFLogxK

U2 - 10.1002/humu.21604

DO - 10.1002/humu.21604

M3 - Article

C2 - 21898661

AN - SCOPUS:84863283896

SN - 1059-7794

VL - 33

SP - 158

EP - 164

JO - Human Mutation

JF - Human Mutation

IS - 1

ER -

Variants in activators and downstream targets of ATM, radiation exposure, and contralateral breast cancer risk in the WECARE study

Abstract

Keywords

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