Pooled analysis of active cigarette smoking and invasive breast cancer risk in 14 cohort studies

Mia M. Gaudet; Brian D. Carter; Louise A. Brinton; Roni T. Falk; Inger T. Gram; Juhua Luo; Roger L. Milne; Sarah J. Nyante; Elisabete Weiderpass; Laura E.Beane Freeman; Dale P. Sandler; Kim Robien; Kristin E. Anderson; Graham G. Giles; Wendy Y. Chen; Diane Feskanich; Tonje Braaten; Claudine Isaacs; Lesley M. Butler; Woon Puay Koh; Alicja Wolk; Hans Olov Adami; Emily White; Karen L. Margolis; Michael J. Thun; Susan M. Gapstur

doi:10.1093/ije/dyw288

Pooled analysis of active cigarette smoking and invasive breast cancer risk in 14 cohort studies

Mia M. Gaudet, Brian D. Carter, Louise A. Brinton, Roni T. Falk, Inger T. Gram, Juhua Luo, Roger L. Milne, Sarah J. Nyante, Elisabete Weiderpass, Laura E.Beane Freeman, Dale P. Sandler, Kim Robien, Kristin E. Anderson, Graham G. Giles, Wendy Y. Chen, Diane Feskanich, Tonje Braaten, Claudine Isaacs, Lesley M. Butler, Woon Puay KohAlicja Wolk, Hans Olov Adami, Emily White, Karen L. Margolis, Michael J. Thun, Susan M. Gapstur

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

67 Scopus citations

Abstract

Background: The 2014 US Surgeon General's report noted research gaps necessary to determine a causal relationship between active cigarette smoking and invasive breast cancer risk, including the role of alcohol consumption, timing of exposure, modification by menopausal status and heterogeneity by oestrogen receptor (ER) status.Methods: To address these issues, we pooled data from 14 cohort studies contributing 934 681 participants (36 060 invasive breast cancer cases). Cox proportional hazard regression models were used to calculate multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs).Results: Smoking duration before first birth was positively associated with risk (P-value for trend = 2 × 10 ^-7 ) with the highest HR for initiation >10 years before first birth (HR = 1.18, CI 1.12-1.24). Effect modification by current alcohol consumption was evident for the association with smoking duration before first birth (P-value=2×10 ^-4 ); compared with never-smoking non-drinkers, initiation >10 years before first birth was associated with risk in every category of alcohol intake, including non-drinkers (HR = 1.15, CI 1.04-1.28) and those who consumed at least three drinks per day (1.85, 1.55-2.21). Associations with smoking before first birth were limited to risk of ER+ breast cancer (P-value for homogeneity=3×10 ^-3 ). Other smoking timing and duration characteristics were associated with risk even after controlling for alcohol, but were not associated with risk in non-drinkers. Effect modification by menopause was not evident.Conclusions: Smoking, particularly if initiated before first birth, was modestly associated with ER+ breast cancer risk that was not confounded by amount of adult alcohol intake. Possible links with breast cancer provide additional motivation for young women to not initiate smoking.

Original language	English (US)
Pages (from-to)	881-893
Number of pages	13
Journal	International journal of epidemiology
Volume	46
Issue number	3
DOIs	https://doi.org/10.1093/ije/dyw288
State	Published - Jun 1 2017

Bibliographical note

Funding Information:
The authors thank the study participants from all the cohorts for their invaluable contributions to this research. The Cancer Prevention Study-II (CPS-II) investigators thank the Study Management Group for their invaluable contributions to this research, and acknowledge the contribution to this study from central cancer registries supported through the Centers for Disease Control and Prevention National Program of Cancer Registries, and cancer registries supported by the National Cancer Institute Surveillance Epidemiology and End Results program. The Iowa Women’s Health Study (IWHS) investigators thank the IWHS study participants for their contributions, and Ching Ping Hong, MS for her assistance in creating the data set for this project. The Melbourne Collaborative Cohort Study (MCCS) was made possible by the contribution of many people, including the original investigators and the diligent team who recruited the participants and who continue working on follow-up. We would also like to express our gratitude to the many thousands of Melbourne residents who continue to participate in the study. We thank Drs. Christine Berg and Philip Prorok (Division of Cancer Prevention, NCI), the Screening Center investigators and staff of the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial, Tom Riley and staff (Information Management Services, Inc.), Barbara O’Brien and staff (Westat, Inc.) and Jackie King (Bioreliance, Rockville) for their contributions to making this study possible. For the Singapore Chinese Health Study (SCHS), we thank Siew-Hong Low of the National University of Singapore for supervising the field work of the Singapore Chinese Health Study, the Singapore Cancer Registry for assistance with the identification of cancer outcomes. We are grateful to the radiologic technologists who have participated in the US Radiologic Technologists (USRT) study; Jerry Reid of the American Registry of Radiologic Technologists for continued support of the study; Diane Kampa and Allison Iwan of the University of Minnesota for cohort follow-up and data management; and Jeremy Miller of Information Management Systems, Inc. for computation and database support. The authors thank the Women’s Health Initiative (WHI) investigators and staff for their dedication, and the study participants for making the program possible. A full listing of WHI investigators can be found at https://www.whi.org/researchers/Documents%20%20 Write%20a%20Paper/WHI%20Investigator%20Short%20List.pdf.

Funding Information:
The pooling project was sponsored by the NCI’s Cohort Consortium and funded by the American Cancer Society. The Agricultural Health Study (AgHealth) was funded by the Intramural Program of the NIH, NCI (Z01 P010119) and the National Institute of Environmental Health Sciences (Z01 ES 049030–11). The American Cancer Society funds the creation, maintenance, and updating of the Cancer Prevention Study-II (CPS-II) cohort. The Iowa Women’s Health Study (IWHS) is supported by a grant from the NCI (R01 CA39742). The Melbourne Collaborative Cohort Study (MCCS) receives core funding from the Cancer Council Victoria and is additionally supported by grants from the Australian NHMRC (209057, 251533, 396414 and 504715). The NIH-AARP Diet and Health Study (AARP) was supported by the Intramural Research Program of the National Cancer Institute, National Institutes of Health. The Nurses’ Health Study 1 (NHS1) was supported by grants from the NCI (UM1CA176726 and P01CA087969–09). The Nurses’ Health Study 2 (NHS2) was supported by a grant from the NCI (R01 CA050385). The Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial is supported by contracts from the NCI. The Singapore Chinese Health Study (SCHS) is supported by grants from the NCI (UM1 CA182876 and R01 CA144034). The Swedish Mammography Cohort (SMC) was supported by the Swedish Research Council, Swedish Council for Working Life and Social Research and the Swedish Cancer Foundation. The Swedish Women’s Lifestyle and Health Study (SWLH) was supported by the Swedish Research Council (grant number 521–2011–2955) and a Distinguished Professor Award at Karolinska Institutet to Hans-Olov Adami, grant number: 2368/10–221. VITamin and Lifestyle (VITAL) study: Dr White was supported by the National Institutes of Health grant K05-CA154337 (National Cancer Institute and Office of Dietary Supplements). The Women’s Health Initiative (WHI) Program is funded by the National Heart, Lung, and Blood Institute, National Institutes of Health, US Department of Health and Human Services through contracts HHSN268201100046C,

Publisher Copyright:
© The Author 2017; all rights reserved.

Keywords

Alcohol
Breast cancer
Tobacco smoking

UN SDGs

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

Publisher link

10.1093/ije/dyw288

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5837778

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Gaudet, M. M., Carter, B. D., Brinton, L. A., Falk, R. T., Gram, I. T., Luo, J., Milne, R. L., Nyante, S. J., Weiderpass, E., Freeman, L. E. B., Sandler, D. P., Robien, K., Anderson, K. E., Giles, G. G., Chen, W. Y., Feskanich, D., Braaten, T., Isaacs, C., Butler, L. M., ... Gapstur, S. M. (2017). Pooled analysis of active cigarette smoking and invasive breast cancer risk in 14 cohort studies. International journal of epidemiology, 46(3), 881-893. https://doi.org/10.1093/ije/dyw288

Gaudet, MM, Carter, BD, Brinton, LA, Falk, RT, Gram, IT, Luo, J, Milne, RL, Nyante, SJ, Weiderpass, E, Freeman, LEB, Sandler, DP, Robien, K, Anderson, KE, Giles, GG, Chen, WY, Feskanich, D, Braaten, T, Isaacs, C, Butler, LM, Koh, WP, Wolk, A, Adami, HO, White, E, Margolis, KL, Thun, MJ & Gapstur, SM 2017, 'Pooled analysis of active cigarette smoking and invasive breast cancer risk in 14 cohort studies', International journal of epidemiology, vol. 46, no. 3, pp. 881-893. https://doi.org/10.1093/ije/dyw288

@article{6ff2c0d019224aa888850d801ae4e332,

title = "Pooled analysis of active cigarette smoking and invasive breast cancer risk in 14 cohort studies",

abstract = " Background: The 2014 US Surgeon General's report noted research gaps necessary to determine a causal relationship between active cigarette smoking and invasive breast cancer risk, including the role of alcohol consumption, timing of exposure, modification by menopausal status and heterogeneity by oestrogen receptor (ER) status.Methods: To address these issues, we pooled data from 14 cohort studies contributing 934 681 participants (36 060 invasive breast cancer cases). Cox proportional hazard regression models were used to calculate multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs).Results: Smoking duration before first birth was positively associated with risk (P-value for trend = 2 × 10 -7 ) with the highest HR for initiation >10 years before first birth (HR = 1.18, CI 1.12-1.24). Effect modification by current alcohol consumption was evident for the association with smoking duration before first birth (P-value=2×10 -4 ); compared with never-smoking non-drinkers, initiation >10 years before first birth was associated with risk in every category of alcohol intake, including non-drinkers (HR = 1.15, CI 1.04-1.28) and those who consumed at least three drinks per day (1.85, 1.55-2.21). Associations with smoking before first birth were limited to risk of ER+ breast cancer (P-value for homogeneity=3×10 -3 ). Other smoking timing and duration characteristics were associated with risk even after controlling for alcohol, but were not associated with risk in non-drinkers. Effect modification by menopause was not evident.Conclusions: Smoking, particularly if initiated before first birth, was modestly associated with ER+ breast cancer risk that was not confounded by amount of adult alcohol intake. Possible links with breast cancer provide additional motivation for young women to not initiate smoking.",

keywords = "Alcohol, Breast cancer, Tobacco smoking",

author = "Gaudet, {Mia M.} and Carter, {Brian D.} and Brinton, {Louise A.} and Falk, {Roni T.} and Gram, {Inger T.} and Juhua Luo and Milne, {Roger L.} and Nyante, {Sarah J.} and Elisabete Weiderpass and Freeman, {Laura E.Beane} and Sandler, {Dale P.} and Kim Robien and Anderson, {Kristin E.} and Giles, {Graham G.} and Chen, {Wendy Y.} and Diane Feskanich and Tonje Braaten and Claudine Isaacs and Butler, {Lesley M.} and Koh, {Woon Puay} and Alicja Wolk and Adami, {Hans Olov} and Emily White and Margolis, {Karen L.} and Thun, {Michael J.} and Gapstur, {Susan M.}",

note = "Funding Information: The authors thank the study participants from all the cohorts for their invaluable contributions to this research. The Cancer Prevention Study-II (CPS-II) investigators thank the Study Management Group for their invaluable contributions to this research, and acknowledge the contribution to this study from central cancer registries supported through the Centers for Disease Control and Prevention National Program of Cancer Registries, and cancer registries supported by the National Cancer Institute Surveillance Epidemiology and End Results program. The Iowa Women{\textquoteright}s Health Study (IWHS) investigators thank the IWHS study participants for their contributions, and Ching Ping Hong, MS for her assistance in creating the data set for this project. The Melbourne Collaborative Cohort Study (MCCS) was made possible by the contribution of many people, including the original investigators and the diligent team who recruited the participants and who continue working on follow-up. We would also like to express our gratitude to the many thousands of Melbourne residents who continue to participate in the study. We thank Drs. Christine Berg and Philip Prorok (Division of Cancer Prevention, NCI), the Screening Center investigators and staff of the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial, Tom Riley and staff (Information Management Services, Inc.), Barbara O{\textquoteright}Brien and staff (Westat, Inc.) and Jackie King (Bioreliance, Rockville) for their contributions to making this study possible. For the Singapore Chinese Health Study (SCHS), we thank Siew-Hong Low of the National University of Singapore for supervising the field work of the Singapore Chinese Health Study, the Singapore Cancer Registry for assistance with the identification of cancer outcomes. We are grateful to the radiologic technologists who have participated in the US Radiologic Technologists (USRT) study; Jerry Reid of the American Registry of Radiologic Technologists for continued support of the study; Diane Kampa and Allison Iwan of the University of Minnesota for cohort follow-up and data management; and Jeremy Miller of Information Management Systems, Inc. for computation and database support. The authors thank the Women{\textquoteright}s Health Initiative (WHI) investigators and staff for their dedication, and the study participants for making the program possible. A full listing of WHI investigators can be found at https://www.whi.org/researchers/Documents%20%20 Write%20a%20Paper/WHI%20Investigator%20Short%20List.pdf. Funding Information: The pooling project was sponsored by the NCI{\textquoteright}s Cohort Consortium and funded by the American Cancer Society. The Agricultural Health Study (AgHealth) was funded by the Intramural Program of the NIH, NCI (Z01 P010119) and the National Institute of Environmental Health Sciences (Z01 ES 049030–11). The American Cancer Society funds the creation, maintenance, and updating of the Cancer Prevention Study-II (CPS-II) cohort. The Iowa Women{\textquoteright}s Health Study (IWHS) is supported by a grant from the NCI (R01 CA39742). The Melbourne Collaborative Cohort Study (MCCS) receives core funding from the Cancer Council Victoria and is additionally supported by grants from the Australian NHMRC (209057, 251533, 396414 and 504715). The NIH-AARP Diet and Health Study (AARP) was supported by the Intramural Research Program of the National Cancer Institute, National Institutes of Health. The Nurses{\textquoteright} Health Study 1 (NHS1) was supported by grants from the NCI (UM1CA176726 and P01CA087969–09). The Nurses{\textquoteright} Health Study 2 (NHS2) was supported by a grant from the NCI (R01 CA050385). The Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial is supported by contracts from the NCI. The Singapore Chinese Health Study (SCHS) is supported by grants from the NCI (UM1 CA182876 and R01 CA144034). The Swedish Mammography Cohort (SMC) was supported by the Swedish Research Council, Swedish Council for Working Life and Social Research and the Swedish Cancer Foundation. The Swedish Women{\textquoteright}s Lifestyle and Health Study (SWLH) was supported by the Swedish Research Council (grant number 521–2011–2955) and a Distinguished Professor Award at Karolinska Institutet to Hans-Olov Adami, grant number: 2368/10–221. VITamin and Lifestyle (VITAL) study: Dr White was supported by the National Institutes of Health grant K05-CA154337 (National Cancer Institute and Office of Dietary Supplements). The Women{\textquoteright}s Health Initiative (WHI) Program is funded by the National Heart, Lung, and Blood Institute, National Institutes of Health, US Department of Health and Human Services through contracts HHSN268201100046C, Publisher Copyright: {\textcopyright} The Author 2017; all rights reserved.",

year = "2017",

month = jun,

day = "1",

doi = "10.1093/ije/dyw288",

language = "English (US)",

volume = "46",

pages = "881--893",

journal = "International journal of epidemiology",

issn = "0300-5771",

publisher = "Oxford University Press",

number = "3",

}

TY - JOUR

T1 - Pooled analysis of active cigarette smoking and invasive breast cancer risk in 14 cohort studies

AU - Gaudet, Mia M.

AU - Carter, Brian D.

AU - Brinton, Louise A.

AU - Falk, Roni T.

AU - Gram, Inger T.

AU - Luo, Juhua

AU - Milne, Roger L.

AU - Nyante, Sarah J.

AU - Weiderpass, Elisabete

AU - Freeman, Laura E.Beane

AU - Sandler, Dale P.

AU - Robien, Kim

AU - Anderson, Kristin E.

AU - Giles, Graham G.

AU - Chen, Wendy Y.

AU - Feskanich, Diane

AU - Braaten, Tonje

AU - Isaacs, Claudine

AU - Butler, Lesley M.

AU - Koh, Woon Puay

AU - Wolk, Alicja

AU - Adami, Hans Olov

AU - White, Emily

AU - Margolis, Karen L.

AU - Thun, Michael J.

AU - Gapstur, Susan M.

N1 - Funding Information: The authors thank the study participants from all the cohorts for their invaluable contributions to this research. The Cancer Prevention Study-II (CPS-II) investigators thank the Study Management Group for their invaluable contributions to this research, and acknowledge the contribution to this study from central cancer registries supported through the Centers for Disease Control and Prevention National Program of Cancer Registries, and cancer registries supported by the National Cancer Institute Surveillance Epidemiology and End Results program. The Iowa Women’s Health Study (IWHS) investigators thank the IWHS study participants for their contributions, and Ching Ping Hong, MS for her assistance in creating the data set for this project. The Melbourne Collaborative Cohort Study (MCCS) was made possible by the contribution of many people, including the original investigators and the diligent team who recruited the participants and who continue working on follow-up. We would also like to express our gratitude to the many thousands of Melbourne residents who continue to participate in the study. We thank Drs. Christine Berg and Philip Prorok (Division of Cancer Prevention, NCI), the Screening Center investigators and staff of the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial, Tom Riley and staff (Information Management Services, Inc.), Barbara O’Brien and staff (Westat, Inc.) and Jackie King (Bioreliance, Rockville) for their contributions to making this study possible. For the Singapore Chinese Health Study (SCHS), we thank Siew-Hong Low of the National University of Singapore for supervising the field work of the Singapore Chinese Health Study, the Singapore Cancer Registry for assistance with the identification of cancer outcomes. We are grateful to the radiologic technologists who have participated in the US Radiologic Technologists (USRT) study; Jerry Reid of the American Registry of Radiologic Technologists for continued support of the study; Diane Kampa and Allison Iwan of the University of Minnesota for cohort follow-up and data management; and Jeremy Miller of Information Management Systems, Inc. for computation and database support. The authors thank the Women’s Health Initiative (WHI) investigators and staff for their dedication, and the study participants for making the program possible. A full listing of WHI investigators can be found at https://www.whi.org/researchers/Documents%20%20 Write%20a%20Paper/WHI%20Investigator%20Short%20List.pdf. Funding Information: The pooling project was sponsored by the NCI’s Cohort Consortium and funded by the American Cancer Society. The Agricultural Health Study (AgHealth) was funded by the Intramural Program of the NIH, NCI (Z01 P010119) and the National Institute of Environmental Health Sciences (Z01 ES 049030–11). The American Cancer Society funds the creation, maintenance, and updating of the Cancer Prevention Study-II (CPS-II) cohort. The Iowa Women’s Health Study (IWHS) is supported by a grant from the NCI (R01 CA39742). The Melbourne Collaborative Cohort Study (MCCS) receives core funding from the Cancer Council Victoria and is additionally supported by grants from the Australian NHMRC (209057, 251533, 396414 and 504715). The NIH-AARP Diet and Health Study (AARP) was supported by the Intramural Research Program of the National Cancer Institute, National Institutes of Health. The Nurses’ Health Study 1 (NHS1) was supported by grants from the NCI (UM1CA176726 and P01CA087969–09). The Nurses’ Health Study 2 (NHS2) was supported by a grant from the NCI (R01 CA050385). The Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial is supported by contracts from the NCI. The Singapore Chinese Health Study (SCHS) is supported by grants from the NCI (UM1 CA182876 and R01 CA144034). The Swedish Mammography Cohort (SMC) was supported by the Swedish Research Council, Swedish Council for Working Life and Social Research and the Swedish Cancer Foundation. The Swedish Women’s Lifestyle and Health Study (SWLH) was supported by the Swedish Research Council (grant number 521–2011–2955) and a Distinguished Professor Award at Karolinska Institutet to Hans-Olov Adami, grant number: 2368/10–221. VITamin and Lifestyle (VITAL) study: Dr White was supported by the National Institutes of Health grant K05-CA154337 (National Cancer Institute and Office of Dietary Supplements). The Women’s Health Initiative (WHI) Program is funded by the National Heart, Lung, and Blood Institute, National Institutes of Health, US Department of Health and Human Services through contracts HHSN268201100046C, Publisher Copyright: © The Author 2017; all rights reserved.

PY - 2017/6/1

Y1 - 2017/6/1

N2 - Background: The 2014 US Surgeon General's report noted research gaps necessary to determine a causal relationship between active cigarette smoking and invasive breast cancer risk, including the role of alcohol consumption, timing of exposure, modification by menopausal status and heterogeneity by oestrogen receptor (ER) status.Methods: To address these issues, we pooled data from 14 cohort studies contributing 934 681 participants (36 060 invasive breast cancer cases). Cox proportional hazard regression models were used to calculate multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs).Results: Smoking duration before first birth was positively associated with risk (P-value for trend = 2 × 10 -7 ) with the highest HR for initiation >10 years before first birth (HR = 1.18, CI 1.12-1.24). Effect modification by current alcohol consumption was evident for the association with smoking duration before first birth (P-value=2×10 -4 ); compared with never-smoking non-drinkers, initiation >10 years before first birth was associated with risk in every category of alcohol intake, including non-drinkers (HR = 1.15, CI 1.04-1.28) and those who consumed at least three drinks per day (1.85, 1.55-2.21). Associations with smoking before first birth were limited to risk of ER+ breast cancer (P-value for homogeneity=3×10 -3 ). Other smoking timing and duration characteristics were associated with risk even after controlling for alcohol, but were not associated with risk in non-drinkers. Effect modification by menopause was not evident.Conclusions: Smoking, particularly if initiated before first birth, was modestly associated with ER+ breast cancer risk that was not confounded by amount of adult alcohol intake. Possible links with breast cancer provide additional motivation for young women to not initiate smoking.

AB - Background: The 2014 US Surgeon General's report noted research gaps necessary to determine a causal relationship between active cigarette smoking and invasive breast cancer risk, including the role of alcohol consumption, timing of exposure, modification by menopausal status and heterogeneity by oestrogen receptor (ER) status.Methods: To address these issues, we pooled data from 14 cohort studies contributing 934 681 participants (36 060 invasive breast cancer cases). Cox proportional hazard regression models were used to calculate multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs).Results: Smoking duration before first birth was positively associated with risk (P-value for trend = 2 × 10 -7 ) with the highest HR for initiation >10 years before first birth (HR = 1.18, CI 1.12-1.24). Effect modification by current alcohol consumption was evident for the association with smoking duration before first birth (P-value=2×10 -4 ); compared with never-smoking non-drinkers, initiation >10 years before first birth was associated with risk in every category of alcohol intake, including non-drinkers (HR = 1.15, CI 1.04-1.28) and those who consumed at least three drinks per day (1.85, 1.55-2.21). Associations with smoking before first birth were limited to risk of ER+ breast cancer (P-value for homogeneity=3×10 -3 ). Other smoking timing and duration characteristics were associated with risk even after controlling for alcohol, but were not associated with risk in non-drinkers. Effect modification by menopause was not evident.Conclusions: Smoking, particularly if initiated before first birth, was modestly associated with ER+ breast cancer risk that was not confounded by amount of adult alcohol intake. Possible links with breast cancer provide additional motivation for young women to not initiate smoking.

KW - Alcohol

KW - Breast cancer

KW - Tobacco smoking

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UR - http://www.scopus.com/inward/citedby.url?scp=85027708307&partnerID=8YFLogxK

U2 - 10.1093/ije/dyw288

DO - 10.1093/ije/dyw288

M3 - Article

C2 - 28031315

AN - SCOPUS:85027708307

SN - 0300-5771

VL - 46

SP - 881

EP - 893

JO - International journal of epidemiology

JF - International journal of epidemiology

IS - 3

ER -

Pooled analysis of active cigarette smoking and invasive breast cancer risk in 14 cohort studies

Abstract

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