Genome-wide Interaction Study with Smoking for Colorectal Cancer Risk Identifies Novel Genetic Loci Related to Tumor Suppression, Inflammation, and Immune Response

Robert Carreras-Torres; Andre E. Kim; Yi Lin; Virginia Díez-Obrero; Stephanie A. Bien; Conghui Qu; Jun Wang; Niki Dimou; Elom K. Aglago; Demetrius Albanes; Volker Arndt; James W. Baurley; Sonja I. Berndt; Stephane Bezieau; D. Timothy Bishop; Emmanouil Bouras; Hermann Brenner; Arif Budiarto; Peter T. Campbell; Graham Casey; Andrew T. Chan; Jenny Chang-Claude; Xuechen Chen; David V. Conti; Christopher H. Dampier; Matthew A.M. Devall; David A. Drew; Jane C. Figueiredo; Steven Gallinger; Graham G. Giles; Stephen B. Gruber; Andrea Gsur; Marc J. Gunter; Tabitha A. Harrison; Akihisa Hidaka; Michael Hoffmeister; Jeroen R. Huyghe; Mark A. Jenkins; Kristina M. Jordahl; Eric Kawaguchi; Temitope O. Keku; Anshul Kundaje; Loic Le Marchand; Juan Pablo Lewinger; Li Li; Bharuno Mahesworo; John L. Morrison; Neil Murphy; Hongmei Nan; Rami Nassir; Polly A. Newcomb; Mireia Obon-Santacana; Shuji Ogino; Jennifer Ose; Rish K. Pai; Julie R. Palmer; Nikos Papadimitriou; Bens Pardamean; Anita R. Peoples; Paul D.P. Pharoah; Elizabeth A. Platz; Gad Rennert; Edward Ruiz-Narvaez; Lori C. Sakoda; Peter C. Scacheri; Stephanie L. Schmit; Robert E. Schoen; Anna Shcherbina; Martha L. Slattery; Mariana C. Stern; Yu Ru Su; Catherine M. Tangen; Duncan C. Thomas; Yu Tian; Konstantinos K. Tsilidis; Cornelia M. Ulrich; Fränzel J.B. van Duijnhoven; Bethany Van Guelpen; Kala Visvanathan; Pavel Vodicka; Tjeng Wawan Cenggoro; Stephanie J. Weinstein; Emily White; Alicja Wolk; Michael O. Woods; Li Hsu; Ulrike Peters; Victor Moreno; W. James Gauderman

doi:10.1158/1055-9965.EPI-22-0763

Genome-wide Interaction Study with Smoking for Colorectal Cancer Risk Identifies Novel Genetic Loci Related to Tumor Suppression, Inflammation, and Immune Response

Robert Carreras-Torres, Andre E. Kim, Yi Lin, Virginia Díez-Obrero, Stephanie A. Bien, Conghui Qu, Jun Wang, Niki Dimou, Elom K. Aglago, Demetrius Albanes, Volker Arndt, James W. Baurley, Sonja I. Berndt, Stephane Bezieau, D. Timothy Bishop, Emmanouil Bouras, Hermann Brenner, Arif Budiarto, Peter T. Campbell, Graham CaseyAndrew T. Chan, Jenny Chang-Claude, Xuechen Chen, David V. Conti, Christopher H. Dampier, Matthew A.M. Devall, David A. Drew, Jane C. Figueiredo, Steven Gallinger, Graham G. Giles, Stephen B. Gruber, Andrea Gsur, Marc J. Gunter, Tabitha A. Harrison, Akihisa Hidaka, Michael Hoffmeister, Jeroen R. Huyghe, Mark A. Jenkins, Kristina M. Jordahl, Eric Kawaguchi, Temitope O. Keku, Anshul Kundaje, Loic Le Marchand, Juan Pablo Lewinger, Li Li, Bharuno Mahesworo, John L. Morrison, Neil Murphy, Hongmei Nan, Rami Nassir, Polly A. Newcomb, Mireia Obon-Santacana, Shuji Ogino, Jennifer Ose, Rish K. Pai, Julie R. Palmer, Nikos Papadimitriou, Bens Pardamean, Anita R. Peoples, Paul D.P. Pharoah, Elizabeth A. Platz, Gad Rennert, Edward Ruiz-Narvaez, Lori C. Sakoda, Peter C. Scacheri, Stephanie L. Schmit, Robert E. Schoen, Anna Shcherbina, Martha L. Slattery, Mariana C. Stern, Yu Ru Su, Catherine M. Tangen, Duncan C. Thomas, Yu Tian, Konstantinos K. Tsilidis, Cornelia M. Ulrich, Fränzel J.B. van Duijnhoven, Bethany Van Guelpen, Kala Visvanathan, Pavel Vodicka, Tjeng Wawan Cenggoro, Stephanie J. Weinstein, Emily White, Alicja Wolk, Michael O. Woods, Li Hsu, Ulrike Peters, Victor Moreno, W. James Gauderman

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

Abstract

Background: Tobacco smoking is an established risk factor for colorectal cancer. However, genetically defined population subgroups may have increased susceptibility to smoking-related effects on colorectal cancer. Methods: A genome-wide interaction scan was performed including 33, 756 colorectal cancer cases and 44, 346 controls from three genetic consortia. Results: Evidence of an interaction was observed between smoking status (ever vs. never smokers) and a locus on 3p12.1 (rs9880919, P = 4.58 × 10^-8), with higher associated risk in subjects carrying the GG genotype [OR, 1.25; 95% confidence interval (CI), 1.20-1.30] compared with the other genotypes (OR <1.17 for GA and AA). Among ever smokers, we observed interactions between smoking intensity (increase in 10 cigarettes smoked per day) and two loci on 6p21.33 (rs4151657, P = 1.72 × 10^-8) and 8q24.23 (rs7005722, P = 2.88 × 10^-8). Subjects carrying the rs4151657 TT genotype showed higher risk (OR, 1.12; 95% CI, 1.09-1.16) compared with the other genotypes (OR <1.06 for TC and CC). Similarly, higher risk was observed among subjects carrying the rs7005722 AA genotype (OR, 1.17; 95% CI, 1.07-1.28) compared with the other genotypes (OR <1.13 for AC and CC). Functional annotation revealed that SNPs in 3p12.1 and 6p21.33 loci were located in regulatory regions, and were associated with expression levels of nearby genes. Genetic models predicting gene expression revealed that smoking parameters were associated with lower colorectal cancer risk with higher expression levels of CADM2 (3p12.1) and ATF6B (6p21.33). Conclusions: Our study identified novel genetic loci that may modulate the risk for colorectal cancer of smoking status and intensity, linked to tumor suppression and immune response. Impact: These findings can guide potential prevention treatments.

Original language	English (US)
Pages (from-to)	315-328
Number of pages	14
Journal	Cancer Epidemiology Biomarkers and Prevention
Volume	32
Issue number	3
DOIs	https://doi.org/10.1158/1055-9965.EPI-22-0763
State	Published - Mar 1 2023
Externally published	Yes

ASJC Scopus subject areas

General Medicine

UN SDGs

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

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10.1158/1055-9965.EPI-22-0763

Cite this

Carreras-Torres, R., Kim, A. E., Lin, Y., Díez-Obrero, V., Bien, S. A., Qu, C., Wang, J., Dimou, N., Aglago, E. K., Albanes, D., Arndt, V., Baurley, J. W., Berndt, S. I., Bezieau, S., Bishop, D. T., Bouras, E., Brenner, H., Budiarto, A., Campbell, P. T., ... Gauderman, W. J. (2023). Genome-wide Interaction Study with Smoking for Colorectal Cancer Risk Identifies Novel Genetic Loci Related to Tumor Suppression, Inflammation, and Immune Response. Cancer Epidemiology Biomarkers and Prevention, 32(3), 315-328. https://doi.org/10.1158/1055-9965.EPI-22-0763

Genome-wide Interaction Study with Smoking for Colorectal Cancer Risk Identifies Novel Genetic Loci Related to Tumor Suppression, Inflammation, and Immune Response. / Carreras-Torres, Robert; Kim, Andre E.; Lin, Yi et al.
In: Cancer Epidemiology Biomarkers and Prevention, Vol. 32, No. 3, 01.03.2023, p. 315-328.

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

Carreras-Torres, R, Kim, AE, Lin, Y, Díez-Obrero, V, Bien, SA, Qu, C, Wang, J, Dimou, N, Aglago, EK, Albanes, D, Arndt, V, Baurley, JW, Berndt, SI, Bezieau, S, Bishop, DT, Bouras, E, Brenner, H, Budiarto, A, Campbell, PT, Casey, G, Chan, AT, Chang-Claude, J, Chen, X, Conti, DV, Dampier, CH, Devall, MAM, Drew, DA, Figueiredo, JC, Gallinger, S, Giles, GG, Gruber, SB, Gsur, A, Gunter, MJ, Harrison, TA, Hidaka, A, Hoffmeister, M, Huyghe, JR, Jenkins, MA, Jordahl, KM, Kawaguchi, E, Keku, TO, Kundaje, A, Le Marchand, L, Lewinger, JP, Li, L, Mahesworo, B, Morrison, JL, Murphy, N, Nan, H, Nassir, R, Newcomb, PA, Obon-Santacana, M, Ogino, S, Ose, J, Pai, RK, Palmer, JR, Papadimitriou, N, Pardamean, B, Peoples, AR, Pharoah, PDP, Platz, EA, Rennert, G, Ruiz-Narvaez, E, Sakoda, LC, Scacheri, PC, Schmit, SL, Schoen, RE, Shcherbina, A, Slattery, ML, Stern, MC, Su, YR, Tangen, CM, Thomas, DC, Tian, Y, Tsilidis, KK, Ulrich, CM, van Duijnhoven, FJB, Van Guelpen, B, Visvanathan, K, Vodicka, P, Cenggoro, TW, Weinstein, SJ, White, E, Wolk, A, Woods, MO, Hsu, L, Peters, U, Moreno, V & Gauderman, WJ 2023, 'Genome-wide Interaction Study with Smoking for Colorectal Cancer Risk Identifies Novel Genetic Loci Related to Tumor Suppression, Inflammation, and Immune Response', Cancer Epidemiology Biomarkers and Prevention, vol. 32, no. 3, pp. 315-328. https://doi.org/10.1158/1055-9965.EPI-22-0763

@article{fffb110e513140118cf61bc2523cfe7d,

title = "Genome-wide Interaction Study with Smoking for Colorectal Cancer Risk Identifies Novel Genetic Loci Related to Tumor Suppression, Inflammation, and Immune Response",

abstract = "Background: Tobacco smoking is an established risk factor for colorectal cancer. However, genetically defined population subgroups may have increased susceptibility to smoking-related effects on colorectal cancer. Methods: A genome-wide interaction scan was performed including 33, 756 colorectal cancer cases and 44, 346 controls from three genetic consortia. Results: Evidence of an interaction was observed between smoking status (ever vs. never smokers) and a locus on 3p12.1 (rs9880919, P = 4.58 × 10-8), with higher associated risk in subjects carrying the GG genotype [OR, 1.25; 95% confidence interval (CI), 1.20-1.30] compared with the other genotypes (OR <1.17 for GA and AA). Among ever smokers, we observed interactions between smoking intensity (increase in 10 cigarettes smoked per day) and two loci on 6p21.33 (rs4151657, P = 1.72 × 10-8) and 8q24.23 (rs7005722, P = 2.88 × 10-8). Subjects carrying the rs4151657 TT genotype showed higher risk (OR, 1.12; 95% CI, 1.09-1.16) compared with the other genotypes (OR <1.06 for TC and CC). Similarly, higher risk was observed among subjects carrying the rs7005722 AA genotype (OR, 1.17; 95% CI, 1.07-1.28) compared with the other genotypes (OR <1.13 for AC and CC). Functional annotation revealed that SNPs in 3p12.1 and 6p21.33 loci were located in regulatory regions, and were associated with expression levels of nearby genes. Genetic models predicting gene expression revealed that smoking parameters were associated with lower colorectal cancer risk with higher expression levels of CADM2 (3p12.1) and ATF6B (6p21.33). Conclusions: Our study identified novel genetic loci that may modulate the risk for colorectal cancer of smoking status and intensity, linked to tumor suppression and immune response. Impact: These findings can guide potential prevention treatments.",

author = "Robert Carreras-Torres and Kim, {Andre E.} and Yi Lin and Virginia D{\'i}ez-Obrero and Bien, {Stephanie A.} and Conghui Qu and Jun Wang and Niki Dimou and Aglago, {Elom K.} and Demetrius Albanes and Volker Arndt and Baurley, {James W.} and Berndt, {Sonja I.} and Stephane Bezieau and Bishop, {D. Timothy} and Emmanouil Bouras and Hermann Brenner and Arif Budiarto and Campbell, {Peter T.} and Graham Casey and Chan, {Andrew T.} and Jenny Chang-Claude and Xuechen Chen and Conti, {David V.} and Dampier, {Christopher H.} and Devall, {Matthew A.M.} and Drew, {David A.} and Figueiredo, {Jane C.} and Steven Gallinger and Giles, {Graham G.} and Gruber, {Stephen B.} and Andrea Gsur and Gunter, {Marc J.} and Harrison, {Tabitha A.} and Akihisa Hidaka and Michael Hoffmeister and Huyghe, {Jeroen R.} and Jenkins, {Mark A.} and Jordahl, {Kristina M.} and Eric Kawaguchi and Keku, {Temitope O.} and Anshul Kundaje and {Le Marchand}, Loic and Lewinger, {Juan Pablo} and Li Li and Bharuno Mahesworo and Morrison, {John L.} and Neil Murphy and Hongmei Nan and Rami Nassir and Newcomb, {Polly A.} and Mireia Obon-Santacana and Shuji Ogino and Jennifer Ose and Pai, {Rish K.} and Palmer, {Julie R.} and Nikos Papadimitriou and Bens Pardamean and Peoples, {Anita R.} and Pharoah, {Paul D.P.} and Platz, {Elizabeth A.} and Gad Rennert and Edward Ruiz-Narvaez and Sakoda, {Lori C.} and Scacheri, {Peter C.} and Schmit, {Stephanie L.} and Schoen, {Robert E.} and Anna Shcherbina and Slattery, {Martha L.} and Stern, {Mariana C.} and Su, {Yu Ru} and Tangen, {Catherine M.} and Thomas, {Duncan C.} and Yu Tian and Tsilidis, {Konstantinos K.} and Ulrich, {Cornelia M.} and {van Duijnhoven}, {Fr{\"a}nzel J.B.} and {Van Guelpen}, Bethany and Kala Visvanathan and Pavel Vodicka and Cenggoro, {Tjeng Wawan} and Weinstein, {Stephanie J.} and Emily White and Alicja Wolk and Woods, {Michael O.} and Li Hsu and Ulrike Peters and Victor Moreno and Gauderman, {W. James}",

note = "Publisher Copyright: {\textcopyright} 2022 American Association for Cancer Research.",

year = "2023",

month = mar,

day = "1",

doi = "10.1158/1055-9965.EPI-22-0763",

language = "English (US)",

volume = "32",

pages = "315--328",

journal = "Cancer Epidemiology Biomarkers and Prevention",

issn = "1055-9965",

publisher = "American Association for Cancer Research Inc.",

number = "3",

}

TY - JOUR

T1 - Genome-wide Interaction Study with Smoking for Colorectal Cancer Risk Identifies Novel Genetic Loci Related to Tumor Suppression, Inflammation, and Immune Response

AU - Carreras-Torres, Robert

AU - Kim, Andre E.

AU - Lin, Yi

AU - Díez-Obrero, Virginia

AU - Bien, Stephanie A.

AU - Qu, Conghui

AU - Wang, Jun

AU - Dimou, Niki

AU - Aglago, Elom K.

AU - Albanes, Demetrius

AU - Arndt, Volker

AU - Baurley, James W.

AU - Berndt, Sonja I.

AU - Bezieau, Stephane

AU - Bishop, D. Timothy

AU - Bouras, Emmanouil

AU - Brenner, Hermann

AU - Budiarto, Arif

AU - Campbell, Peter T.

AU - Casey, Graham

AU - Chan, Andrew T.

AU - Chang-Claude, Jenny

AU - Chen, Xuechen

AU - Conti, David V.

AU - Dampier, Christopher H.

AU - Devall, Matthew A.M.

AU - Drew, David A.

AU - Figueiredo, Jane C.

AU - Gallinger, Steven

AU - Giles, Graham G.

AU - Gruber, Stephen B.

AU - Gsur, Andrea

AU - Gunter, Marc J.

AU - Harrison, Tabitha A.

AU - Hidaka, Akihisa

AU - Hoffmeister, Michael

AU - Huyghe, Jeroen R.

AU - Jenkins, Mark A.

AU - Jordahl, Kristina M.

AU - Kawaguchi, Eric

AU - Keku, Temitope O.

AU - Kundaje, Anshul

AU - Le Marchand, Loic

AU - Lewinger, Juan Pablo

AU - Li, Li

AU - Mahesworo, Bharuno

AU - Morrison, John L.

AU - Murphy, Neil

AU - Nan, Hongmei

AU - Nassir, Rami

AU - Newcomb, Polly A.

AU - Obon-Santacana, Mireia

AU - Ogino, Shuji

AU - Ose, Jennifer

AU - Pai, Rish K.

AU - Palmer, Julie R.

AU - Papadimitriou, Nikos

AU - Pardamean, Bens

AU - Peoples, Anita R.

AU - Pharoah, Paul D.P.

AU - Platz, Elizabeth A.

AU - Rennert, Gad

AU - Ruiz-Narvaez, Edward

AU - Sakoda, Lori C.

AU - Scacheri, Peter C.

AU - Schmit, Stephanie L.

AU - Schoen, Robert E.

AU - Shcherbina, Anna

AU - Slattery, Martha L.

AU - Stern, Mariana C.

AU - Su, Yu Ru

AU - Tangen, Catherine M.

AU - Thomas, Duncan C.

AU - Tian, Yu

AU - Tsilidis, Konstantinos K.

AU - Ulrich, Cornelia M.

AU - van Duijnhoven, Fränzel J.B.

AU - Van Guelpen, Bethany

AU - Visvanathan, Kala

AU - Vodicka, Pavel

AU - Cenggoro, Tjeng Wawan

AU - Weinstein, Stephanie J.

AU - White, Emily

AU - Wolk, Alicja

AU - Woods, Michael O.

AU - Hsu, Li

AU - Peters, Ulrike

AU - Moreno, Victor

AU - Gauderman, W. James

PY - 2023/3/1

Y1 - 2023/3/1

N2 - Background: Tobacco smoking is an established risk factor for colorectal cancer. However, genetically defined population subgroups may have increased susceptibility to smoking-related effects on colorectal cancer. Methods: A genome-wide interaction scan was performed including 33, 756 colorectal cancer cases and 44, 346 controls from three genetic consortia. Results: Evidence of an interaction was observed between smoking status (ever vs. never smokers) and a locus on 3p12.1 (rs9880919, P = 4.58 × 10-8), with higher associated risk in subjects carrying the GG genotype [OR, 1.25; 95% confidence interval (CI), 1.20-1.30] compared with the other genotypes (OR <1.17 for GA and AA). Among ever smokers, we observed interactions between smoking intensity (increase in 10 cigarettes smoked per day) and two loci on 6p21.33 (rs4151657, P = 1.72 × 10-8) and 8q24.23 (rs7005722, P = 2.88 × 10-8). Subjects carrying the rs4151657 TT genotype showed higher risk (OR, 1.12; 95% CI, 1.09-1.16) compared with the other genotypes (OR <1.06 for TC and CC). Similarly, higher risk was observed among subjects carrying the rs7005722 AA genotype (OR, 1.17; 95% CI, 1.07-1.28) compared with the other genotypes (OR <1.13 for AC and CC). Functional annotation revealed that SNPs in 3p12.1 and 6p21.33 loci were located in regulatory regions, and were associated with expression levels of nearby genes. Genetic models predicting gene expression revealed that smoking parameters were associated with lower colorectal cancer risk with higher expression levels of CADM2 (3p12.1) and ATF6B (6p21.33). Conclusions: Our study identified novel genetic loci that may modulate the risk for colorectal cancer of smoking status and intensity, linked to tumor suppression and immune response. Impact: These findings can guide potential prevention treatments.

AB - Background: Tobacco smoking is an established risk factor for colorectal cancer. However, genetically defined population subgroups may have increased susceptibility to smoking-related effects on colorectal cancer. Methods: A genome-wide interaction scan was performed including 33, 756 colorectal cancer cases and 44, 346 controls from three genetic consortia. Results: Evidence of an interaction was observed between smoking status (ever vs. never smokers) and a locus on 3p12.1 (rs9880919, P = 4.58 × 10-8), with higher associated risk in subjects carrying the GG genotype [OR, 1.25; 95% confidence interval (CI), 1.20-1.30] compared with the other genotypes (OR <1.17 for GA and AA). Among ever smokers, we observed interactions between smoking intensity (increase in 10 cigarettes smoked per day) and two loci on 6p21.33 (rs4151657, P = 1.72 × 10-8) and 8q24.23 (rs7005722, P = 2.88 × 10-8). Subjects carrying the rs4151657 TT genotype showed higher risk (OR, 1.12; 95% CI, 1.09-1.16) compared with the other genotypes (OR <1.06 for TC and CC). Similarly, higher risk was observed among subjects carrying the rs7005722 AA genotype (OR, 1.17; 95% CI, 1.07-1.28) compared with the other genotypes (OR <1.13 for AC and CC). Functional annotation revealed that SNPs in 3p12.1 and 6p21.33 loci were located in regulatory regions, and were associated with expression levels of nearby genes. Genetic models predicting gene expression revealed that smoking parameters were associated with lower colorectal cancer risk with higher expression levels of CADM2 (3p12.1) and ATF6B (6p21.33). Conclusions: Our study identified novel genetic loci that may modulate the risk for colorectal cancer of smoking status and intensity, linked to tumor suppression and immune response. Impact: These findings can guide potential prevention treatments.

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UR - http://www.scopus.com/inward/citedby.url?scp=85149998963&partnerID=8YFLogxK

U2 - 10.1158/1055-9965.EPI-22-0763

DO - 10.1158/1055-9965.EPI-22-0763

M3 - Article

C2 - 36576985

AN - SCOPUS:85149998963

SN - 1055-9965

VL - 32

SP - 315

EP - 328

JO - Cancer Epidemiology Biomarkers and Prevention

JF - Cancer Epidemiology Biomarkers and Prevention

IS - 3

ER -

Genome-wide Interaction Study with Smoking for Colorectal Cancer Risk Identifies Novel Genetic Loci Related to Tumor Suppression, Inflammation, and Immune Response

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