Common genetic polymorphisms modify the effect of smoking on absolute risk of bladder cancer

Montserrat Garcia-Closas, Nathaniel Rothman, Jonine D. Figueroa, Ludmila Prokunina-Olsson, Summer S. Han, Dalsu Baris, Eric J. Jacobs, Nuria Malats, Immaculata De Vivo, Demetrius Albanes, Mark P. Purdue, Sapna Sharma, Yi Ping Fu, Manolis Kogevinas, Zhaoming Wang, Wei Tang, Adonina Tardon, Consol Serra, Alfredo Carrato, Reina García-ClosasJosep Lloreta, Alison Johnson, Molly Schwenn, Margaret R. Karagas, Alan Schned, Gerald Andriole, Robert Grubb, Amanda Black, Susan M. Gapstur, Michael Thun, William Ryan Diver, Stephanie J. Weinstein, Jarmo Virtamo, David J. Hunter, Neil Caporaso, Maria Teresa Landi, Amy Hutchinson, Laurie Burdett, Kevin B. Jacobs, Meredith Yeager, Joseph F. Fraumeni, Stephen J. Chanock, Debra T. Silverman, Nilanjan Chatterjee

Research output: Contribution to journalArticle

Abstract

Bladder cancer results from the combined effects of environmental and genetic factors, smoking being the strongest risk factor. Evaluating absolute risks resulting from the joint effects of smoking and genetic factors is critical to assess the public health relevance of genetic information. Analyses included up to 3,942 cases and 5,680 controls of European background in seven studies. We tested for multiplicative and additive interactions between smoking and 12 susceptibility loci, individually and combined as a polygenic risk score (PRS). Thirty-year absolute risks and risk differences by levels of the PRS were estimated for U.S. males aged 50 years. Six of 12 variants showed significant additive gene-environment interactions, most notably NAT2(P = 7 × 10 -4) and UGT1A6 (P = 8 × 10-4). The 30-year absolute risk of bladder cancer in U.S. males was 6.2% for all current smokers. This risk ranged from 2.9% for current smokers in the lowest quartile of the PRS to 9.9% for current smokers in the upper quartile. Risk difference estimates indicated that 8,200 cases would be prevented if elimination of smoking occurred in 100,000 men in the upper PRS quartile compared with 2,000 cases prevented by a similar effort in the lowest PRS quartile (Padditive = 1 × 10 -4). Thus, the potential impact of eliminating smoking on the number of bladder cancer cases prevented is larger for individuals at higher than lower genetic risk. Our findings could have implications for targeted prevention strategies. However, other smoking-related diseases, as well as practical and ethical considerations, need to be considered before any recommendations could be made.

Original languageEnglish (US)
Pages (from-to)2211-2220
Number of pages10
JournalCancer Research
Volume73
Issue number7
DOIs
StatePublished - Apr 1 2013
Externally publishedYes

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Genetic Polymorphisms
Urinary Bladder Neoplasms
Smoking
Gene-Environment Interaction
Public Health

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Garcia-Closas, M., Rothman, N., Figueroa, J. D., Prokunina-Olsson, L., Han, S. S., Baris, D., ... Chatterjee, N. (2013). Common genetic polymorphisms modify the effect of smoking on absolute risk of bladder cancer. Cancer Research, 73(7), 2211-2220. https://doi.org/10.1158/0008-5472.CAN-12-2388

Common genetic polymorphisms modify the effect of smoking on absolute risk of bladder cancer. / Garcia-Closas, Montserrat; Rothman, Nathaniel; Figueroa, Jonine D.; Prokunina-Olsson, Ludmila; Han, Summer S.; Baris, Dalsu; Jacobs, Eric J.; Malats, Nuria; De Vivo, Immaculata; Albanes, Demetrius; Purdue, Mark P.; Sharma, Sapna; Fu, Yi Ping; Kogevinas, Manolis; Wang, Zhaoming; Tang, Wei; Tardon, Adonina; Serra, Consol; Carrato, Alfredo; García-Closas, Reina; Lloreta, Josep; Johnson, Alison; Schwenn, Molly; Karagas, Margaret R.; Schned, Alan; Andriole, Gerald; Grubb, Robert; Black, Amanda; Gapstur, Susan M.; Thun, Michael; Diver, William Ryan; Weinstein, Stephanie J.; Virtamo, Jarmo; Hunter, David J.; Caporaso, Neil; Landi, Maria Teresa; Hutchinson, Amy; Burdett, Laurie; Jacobs, Kevin B.; Yeager, Meredith; Fraumeni, Joseph F.; Chanock, Stephen J.; Silverman, Debra T.; Chatterjee, Nilanjan.

In: Cancer Research, Vol. 73, No. 7, 01.04.2013, p. 2211-2220.

Research output: Contribution to journalArticle

Garcia-Closas, M, Rothman, N, Figueroa, JD, Prokunina-Olsson, L, Han, SS, Baris, D, Jacobs, EJ, Malats, N, De Vivo, I, Albanes, D, Purdue, MP, Sharma, S, Fu, YP, Kogevinas, M, Wang, Z, Tang, W, Tardon, A, Serra, C, Carrato, A, García-Closas, R, Lloreta, J, Johnson, A, Schwenn, M, Karagas, MR, Schned, A, Andriole, G, Grubb, R, Black, A, Gapstur, SM, Thun, M, Diver, WR, Weinstein, SJ, Virtamo, J, Hunter, DJ, Caporaso, N, Landi, MT, Hutchinson, A, Burdett, L, Jacobs, KB, Yeager, M, Fraumeni, JF, Chanock, SJ, Silverman, DT & Chatterjee, N 2013, 'Common genetic polymorphisms modify the effect of smoking on absolute risk of bladder cancer', Cancer Research, vol. 73, no. 7, pp. 2211-2220. https://doi.org/10.1158/0008-5472.CAN-12-2388
Garcia-Closas M, Rothman N, Figueroa JD, Prokunina-Olsson L, Han SS, Baris D et al. Common genetic polymorphisms modify the effect of smoking on absolute risk of bladder cancer. Cancer Research. 2013 Apr 1;73(7):2211-2220. https://doi.org/10.1158/0008-5472.CAN-12-2388
Garcia-Closas, Montserrat ; Rothman, Nathaniel ; Figueroa, Jonine D. ; Prokunina-Olsson, Ludmila ; Han, Summer S. ; Baris, Dalsu ; Jacobs, Eric J. ; Malats, Nuria ; De Vivo, Immaculata ; Albanes, Demetrius ; Purdue, Mark P. ; Sharma, Sapna ; Fu, Yi Ping ; Kogevinas, Manolis ; Wang, Zhaoming ; Tang, Wei ; Tardon, Adonina ; Serra, Consol ; Carrato, Alfredo ; García-Closas, Reina ; Lloreta, Josep ; Johnson, Alison ; Schwenn, Molly ; Karagas, Margaret R. ; Schned, Alan ; Andriole, Gerald ; Grubb, Robert ; Black, Amanda ; Gapstur, Susan M. ; Thun, Michael ; Diver, William Ryan ; Weinstein, Stephanie J. ; Virtamo, Jarmo ; Hunter, David J. ; Caporaso, Neil ; Landi, Maria Teresa ; Hutchinson, Amy ; Burdett, Laurie ; Jacobs, Kevin B. ; Yeager, Meredith ; Fraumeni, Joseph F. ; Chanock, Stephen J. ; Silverman, Debra T. ; Chatterjee, Nilanjan. / Common genetic polymorphisms modify the effect of smoking on absolute risk of bladder cancer. In: Cancer Research. 2013 ; Vol. 73, No. 7. pp. 2211-2220.
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abstract = "Bladder cancer results from the combined effects of environmental and genetic factors, smoking being the strongest risk factor. Evaluating absolute risks resulting from the joint effects of smoking and genetic factors is critical to assess the public health relevance of genetic information. Analyses included up to 3,942 cases and 5,680 controls of European background in seven studies. We tested for multiplicative and additive interactions between smoking and 12 susceptibility loci, individually and combined as a polygenic risk score (PRS). Thirty-year absolute risks and risk differences by levels of the PRS were estimated for U.S. males aged 50 years. Six of 12 variants showed significant additive gene-environment interactions, most notably NAT2(P = 7 × 10 -4) and UGT1A6 (P = 8 × 10-4). The 30-year absolute risk of bladder cancer in U.S. males was 6.2{\%} for all current smokers. This risk ranged from 2.9{\%} for current smokers in the lowest quartile of the PRS to 9.9{\%} for current smokers in the upper quartile. Risk difference estimates indicated that 8,200 cases would be prevented if elimination of smoking occurred in 100,000 men in the upper PRS quartile compared with 2,000 cases prevented by a similar effort in the lowest PRS quartile (Padditive = 1 × 10 -4). Thus, the potential impact of eliminating smoking on the number of bladder cancer cases prevented is larger for individuals at higher than lower genetic risk. Our findings could have implications for targeted prevention strategies. However, other smoking-related diseases, as well as practical and ethical considerations, need to be considered before any recommendations could be made.",
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T1 - Common genetic polymorphisms modify the effect of smoking on absolute risk of bladder cancer

AU - Garcia-Closas, Montserrat

AU - Rothman, Nathaniel

AU - Figueroa, Jonine D.

AU - Prokunina-Olsson, Ludmila

AU - Han, Summer S.

AU - Baris, Dalsu

AU - Jacobs, Eric J.

AU - Malats, Nuria

AU - De Vivo, Immaculata

AU - Albanes, Demetrius

AU - Purdue, Mark P.

AU - Sharma, Sapna

AU - Fu, Yi Ping

AU - Kogevinas, Manolis

AU - Wang, Zhaoming

AU - Tang, Wei

AU - Tardon, Adonina

AU - Serra, Consol

AU - Carrato, Alfredo

AU - García-Closas, Reina

AU - Lloreta, Josep

AU - Johnson, Alison

AU - Schwenn, Molly

AU - Karagas, Margaret R.

AU - Schned, Alan

AU - Andriole, Gerald

AU - Grubb, Robert

AU - Black, Amanda

AU - Gapstur, Susan M.

AU - Thun, Michael

AU - Diver, William Ryan

AU - Weinstein, Stephanie J.

AU - Virtamo, Jarmo

AU - Hunter, David J.

AU - Caporaso, Neil

AU - Landi, Maria Teresa

AU - Hutchinson, Amy

AU - Burdett, Laurie

AU - Jacobs, Kevin B.

AU - Yeager, Meredith

AU - Fraumeni, Joseph F.

AU - Chanock, Stephen J.

AU - Silverman, Debra T.

AU - Chatterjee, Nilanjan

PY - 2013/4/1

Y1 - 2013/4/1

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