Genetic polymorphisms in 15q25 and 19q13 loci, cotinine levels, and risk of lung cancer in EPIC

Maria N. Timofeeva; James D. McKay; George Davey Smith; Mattias Johansson; Graham B. Byrnes; Amélie Chabrier; Caroline Relton; Per Magne Ueland; Stein Emil Vollset; Øivind Midttun; Ottar Nygård; Nadia Slimani; Isabelle Romieu; Françoise Clavel-Chapelon; Marie Christine Boutron-Ruault; Guy Fagherazzi; Rudolf Kaaks; Birgit Teucher; Heiner Boeing; Cornelia Weikert; H. Bas Bueno-de-Mesquita; Carla Van Gils; Petra H.M. Peeters; Antonio Agudo; Aurelio Barricarte; Jose Maria Huerta; Laudina Rodríguez; Maria José Sánchez; Nerea Larrañaga; Kay Tee Khaw; Nick Wareham; Naomi E. Allen; Ruth C. Travis; Valentina Gallo; Teresa Norat; Vittorio Krogh; Giovanna Masala; Salvatore Panico; Carlotta Sacerdote; Rosario Tumino; Antonia Trichopoulou; Pagona Lagiou; Dimitrios Trichopoulos; Torgny Rasmuson; Göran Hallmans; Elio Riboli; Paolo Vineis; Paul Brennan

doi:10.1158/1055-9965.EPI-11-0496

Genetic polymorphisms in 15q25 and 19q13 loci, cotinine levels, and risk of lung cancer in EPIC

Maria N. Timofeeva, James D. McKay, George Davey Smith, Mattias Johansson, Graham B. Byrnes, Amélie Chabrier, Caroline Relton, Per Magne Ueland, Stein Emil Vollset, Øivind Midttun, Ottar Nygård, Nadia Slimani, Isabelle Romieu, Françoise Clavel-Chapelon, Marie Christine Boutron-Ruault, Guy Fagherazzi, Rudolf Kaaks, Birgit Teucher, Heiner Boeing, Cornelia WeikertH. Bas Bueno-de-Mesquita, Carla Van Gils, Petra H.M. Peeters, Antonio Agudo, Aurelio Barricarte, Jose Maria Huerta, Laudina Rodríguez, Maria José Sánchez, Nerea Larrañaga, Kay Tee Khaw, Nick Wareham, Naomi E. Allen, Ruth C. Travis, Valentina Gallo, Teresa Norat, Vittorio Krogh, Giovanna Masala, Salvatore Panico, Carlotta Sacerdote, Rosario Tumino, Antonia Trichopoulou, Pagona Lagiou, Dimitrios Trichopoulos, Torgny Rasmuson, Göran Hallmans, Elio Riboli, Paolo Vineis, Paul Brennan^*

^*Corresponding author for this work

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

59 Citations (Scopus)

Abstract

Backgrounds: Multiple polymorphisms affecting smoking behavior have been identified through genomewide association studies. Circulating levels of the nicotine metabolite cotinine is a marker of recent smoking exposure. Hence, genetic variants influencing smoking behavior are expected to be associated with cotinine levels. Methods: We conducted an analysis in a lung cancer case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. We investigated the effects of singlenucleotide polymorphisms (SNP) previously associated with smoking behavior on (i) circulating cotinine and (ii) lung cancer risk. A total of 894 cases and 1,805 controls were analyzed for cotinine and genotyped for 10 polymorphisms on 7p14, 8p11, 10q23, 15q25, and 19q13. Results: Two variants in the nicotinic acetylcholine receptor subunit genes CHRNA5 and CHRNA3 on 15q25, rs16969968 and rs578776, were associated with cotinine (P = 0.001 and 0.03, respectively) in current smokers and with lung cancer risk (P < 0.001 and P = 0.001, respectively). Two 19q13 variants, rs7937 and rs4105144, were associated with increased cotinine (P = 0.003 and P < 0.001, respectively) but decreased lung cancer risk (P = 0.01 for both, after adjusting for cotinine). Variants in 7p14, 8p11, and 10q23 were not associated with cotinine or lung cancer risk.Conclusions: 15q25 and 19q13 SNPs were associated with circulating cotinine. The directions of association for 15q25 variants with cotinine were in accordance with that expected of lung cancer risk, whereas SNPs on 19q13 displayed contrasting associations of cotinine and lung cancer that require further investigation. Impact: This study is the largest to date investigating the effects of polymorphisms affecting smoking behavior on lung cancer risk using circulating cotinine measures as proxies for recent smoking behavior.

Original language	English
Pages (from-to)	2250-2261
Number of pages	12
Journal	Cancer Epidemiology Biomarkers and Prevention
Volume	20
Issue number	10
DOIs	https://doi.org/10.1158/1055-9965.EPI-11-0496
Publication status	Published - Oct 2011
Externally published	Yes

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10.1158/1055-9965.EPI-11-0496

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Timofeeva, M. N., McKay, J. D., Smith, G. D., Johansson, M., Byrnes, G. B., Chabrier, A., Relton, C., Ueland, P. M., Vollset, S. E., Midttun, Ø., Nygård, O., Slimani, N., Romieu, I., Clavel-Chapelon, F., Boutron-Ruault, M. C., Fagherazzi, G., Kaaks, R., Teucher, B., Boeing, H., ... Brennan, P. (2011). Genetic polymorphisms in 15q25 and 19q13 loci, cotinine levels, and risk of lung cancer in EPIC. Cancer Epidemiology Biomarkers and Prevention, 20(10), 2250-2261. https://doi.org/10.1158/1055-9965.EPI-11-0496

@article{e8c6846820674b91b119baa73b93af18,

title = "Genetic polymorphisms in 15q25 and 19q13 loci, cotinine levels, and risk of lung cancer in EPIC",

abstract = "Backgrounds: Multiple polymorphisms affecting smoking behavior have been identified through genomewide association studies. Circulating levels of the nicotine metabolite cotinine is a marker of recent smoking exposure. Hence, genetic variants influencing smoking behavior are expected to be associated with cotinine levels. Methods: We conducted an analysis in a lung cancer case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. We investigated the effects of singlenucleotide polymorphisms (SNP) previously associated with smoking behavior on (i) circulating cotinine and (ii) lung cancer risk. A total of 894 cases and 1,805 controls were analyzed for cotinine and genotyped for 10 polymorphisms on 7p14, 8p11, 10q23, 15q25, and 19q13. Results: Two variants in the nicotinic acetylcholine receptor subunit genes CHRNA5 and CHRNA3 on 15q25, rs16969968 and rs578776, were associated with cotinine (P = 0.001 and 0.03, respectively) in current smokers and with lung cancer risk (P < 0.001 and P = 0.001, respectively). Two 19q13 variants, rs7937 and rs4105144, were associated with increased cotinine (P = 0.003 and P < 0.001, respectively) but decreased lung cancer risk (P = 0.01 for both, after adjusting for cotinine). Variants in 7p14, 8p11, and 10q23 were not associated with cotinine or lung cancer risk.Conclusions: 15q25 and 19q13 SNPs were associated with circulating cotinine. The directions of association for 15q25 variants with cotinine were in accordance with that expected of lung cancer risk, whereas SNPs on 19q13 displayed contrasting associations of cotinine and lung cancer that require further investigation. Impact: This study is the largest to date investigating the effects of polymorphisms affecting smoking behavior on lung cancer risk using circulating cotinine measures as proxies for recent smoking behavior.",

author = "Timofeeva, {Maria N.} and McKay, {James D.} and Smith, {George Davey} and Mattias Johansson and Byrnes, {Graham B.} and Am{\'e}lie Chabrier and Caroline Relton and Ueland, {Per Magne} and Vollset, {Stein Emil} and {\O}ivind Midttun and Ottar Nyg{\aa}rd and Nadia Slimani and Isabelle Romieu and Fran{\c c}oise Clavel-Chapelon and Boutron-Ruault, {Marie Christine} and Guy Fagherazzi and Rudolf Kaaks and Birgit Teucher and Heiner Boeing and Cornelia Weikert and Bueno-de-Mesquita, {H. Bas} and {Van Gils}, Carla and Peeters, {Petra H.M.} and Antonio Agudo and Aurelio Barricarte and Huerta, {Jose Maria} and Laudina Rodr{\'i}guez and S{\'a}nchez, {Maria Jos{\'e}} and Nerea Larra{\~n}aga and Khaw, {Kay Tee} and Nick Wareham and Allen, {Naomi E.} and Travis, {Ruth C.} and Valentina Gallo and Teresa Norat and Vittorio Krogh and Giovanna Masala and Salvatore Panico and Carlotta Sacerdote and Rosario Tumino and Antonia Trichopoulou and Pagona Lagiou and Dimitrios Trichopoulos and Torgny Rasmuson and G{\"o}ran Hallmans and Elio Riboli and Paolo Vineis and Paul Brennan",

year = "2011",

month = oct,

doi = "10.1158/1055-9965.EPI-11-0496",

language = "English",

volume = "20",

pages = "2250--2261",

journal = "Cancer Epidemiology Biomarkers and Prevention",

issn = "1055-9965",

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

number = "10",

}

Timofeeva, MN, McKay, JD, Smith, GD, Johansson, M, Byrnes, GB, Chabrier, A, Relton, C, Ueland, PM, Vollset, SE, Midttun, Ø, Nygård, O, Slimani, N, Romieu, I, Clavel-Chapelon, F, Boutron-Ruault, MC, Fagherazzi, G, Kaaks, R, Teucher, B, Boeing, H, Weikert, C, Bueno-de-Mesquita, HB, Van Gils, C, Peeters, PHM, Agudo, A, Barricarte, A, Huerta, JM, Rodríguez, L, Sánchez, MJ, Larrañaga, N, Khaw, KT, Wareham, N, Allen, NE, Travis, RC, Gallo, V, Norat, T, Krogh, V, Masala, G, Panico, S, Sacerdote, C, Tumino, R, Trichopoulou, A, Lagiou, P, Trichopoulos, D, Rasmuson, T, Hallmans, G, Riboli, E, Vineis, P & Brennan, P 2011, 'Genetic polymorphisms in 15q25 and 19q13 loci, cotinine levels, and risk of lung cancer in EPIC', Cancer Epidemiology Biomarkers and Prevention, vol. 20, no. 10, pp. 2250-2261. https://doi.org/10.1158/1055-9965.EPI-11-0496

TY - JOUR

T1 - Genetic polymorphisms in 15q25 and 19q13 loci, cotinine levels, and risk of lung cancer in EPIC

AU - Timofeeva, Maria N.

AU - McKay, James D.

AU - Smith, George Davey

AU - Johansson, Mattias

AU - Byrnes, Graham B.

AU - Chabrier, Amélie

AU - Relton, Caroline

AU - Ueland, Per Magne

AU - Vollset, Stein Emil

AU - Midttun, Øivind

AU - Nygård, Ottar

AU - Slimani, Nadia

AU - Romieu, Isabelle

AU - Clavel-Chapelon, Françoise

AU - Boutron-Ruault, Marie Christine

AU - Fagherazzi, Guy

AU - Kaaks, Rudolf

AU - Teucher, Birgit

AU - Boeing, Heiner

AU - Weikert, Cornelia

AU - Bueno-de-Mesquita, H. Bas

AU - Van Gils, Carla

AU - Peeters, Petra H.M.

AU - Agudo, Antonio

AU - Barricarte, Aurelio

AU - Huerta, Jose Maria

AU - Rodríguez, Laudina

AU - Sánchez, Maria José

AU - Larrañaga, Nerea

AU - Khaw, Kay Tee

AU - Wareham, Nick

AU - Allen, Naomi E.

AU - Travis, Ruth C.

AU - Gallo, Valentina

AU - Norat, Teresa

AU - Krogh, Vittorio

AU - Masala, Giovanna

AU - Panico, Salvatore

AU - Sacerdote, Carlotta

AU - Tumino, Rosario

AU - Trichopoulou, Antonia

AU - Lagiou, Pagona

AU - Trichopoulos, Dimitrios

AU - Rasmuson, Torgny

AU - Hallmans, Göran

AU - Riboli, Elio

AU - Vineis, Paolo

AU - Brennan, Paul

PY - 2011/10

Y1 - 2011/10

N2 - Backgrounds: Multiple polymorphisms affecting smoking behavior have been identified through genomewide association studies. Circulating levels of the nicotine metabolite cotinine is a marker of recent smoking exposure. Hence, genetic variants influencing smoking behavior are expected to be associated with cotinine levels. Methods: We conducted an analysis in a lung cancer case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. We investigated the effects of singlenucleotide polymorphisms (SNP) previously associated with smoking behavior on (i) circulating cotinine and (ii) lung cancer risk. A total of 894 cases and 1,805 controls were analyzed for cotinine and genotyped for 10 polymorphisms on 7p14, 8p11, 10q23, 15q25, and 19q13. Results: Two variants in the nicotinic acetylcholine receptor subunit genes CHRNA5 and CHRNA3 on 15q25, rs16969968 and rs578776, were associated with cotinine (P = 0.001 and 0.03, respectively) in current smokers and with lung cancer risk (P < 0.001 and P = 0.001, respectively). Two 19q13 variants, rs7937 and rs4105144, were associated with increased cotinine (P = 0.003 and P < 0.001, respectively) but decreased lung cancer risk (P = 0.01 for both, after adjusting for cotinine). Variants in 7p14, 8p11, and 10q23 were not associated with cotinine or lung cancer risk.Conclusions: 15q25 and 19q13 SNPs were associated with circulating cotinine. The directions of association for 15q25 variants with cotinine were in accordance with that expected of lung cancer risk, whereas SNPs on 19q13 displayed contrasting associations of cotinine and lung cancer that require further investigation. Impact: This study is the largest to date investigating the effects of polymorphisms affecting smoking behavior on lung cancer risk using circulating cotinine measures as proxies for recent smoking behavior.

AB - Backgrounds: Multiple polymorphisms affecting smoking behavior have been identified through genomewide association studies. Circulating levels of the nicotine metabolite cotinine is a marker of recent smoking exposure. Hence, genetic variants influencing smoking behavior are expected to be associated with cotinine levels. Methods: We conducted an analysis in a lung cancer case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. We investigated the effects of singlenucleotide polymorphisms (SNP) previously associated with smoking behavior on (i) circulating cotinine and (ii) lung cancer risk. A total of 894 cases and 1,805 controls were analyzed for cotinine and genotyped for 10 polymorphisms on 7p14, 8p11, 10q23, 15q25, and 19q13. Results: Two variants in the nicotinic acetylcholine receptor subunit genes CHRNA5 and CHRNA3 on 15q25, rs16969968 and rs578776, were associated with cotinine (P = 0.001 and 0.03, respectively) in current smokers and with lung cancer risk (P < 0.001 and P = 0.001, respectively). Two 19q13 variants, rs7937 and rs4105144, were associated with increased cotinine (P = 0.003 and P < 0.001, respectively) but decreased lung cancer risk (P = 0.01 for both, after adjusting for cotinine). Variants in 7p14, 8p11, and 10q23 were not associated with cotinine or lung cancer risk.Conclusions: 15q25 and 19q13 SNPs were associated with circulating cotinine. The directions of association for 15q25 variants with cotinine were in accordance with that expected of lung cancer risk, whereas SNPs on 19q13 displayed contrasting associations of cotinine and lung cancer that require further investigation. Impact: This study is the largest to date investigating the effects of polymorphisms affecting smoking behavior on lung cancer risk using circulating cotinine measures as proxies for recent smoking behavior.

UR - http://www.scopus.com/inward/record.url?scp=80053484625&partnerID=8YFLogxK

U2 - 10.1158/1055-9965.EPI-11-0496

DO - 10.1158/1055-9965.EPI-11-0496

M3 - Article

C2 - 21862624

AN - SCOPUS:80053484625

SN - 1055-9965

VL - 20

SP - 2250

EP - 2261

JO - Cancer Epidemiology Biomarkers and Prevention

JF - Cancer Epidemiology Biomarkers and Prevention

IS - 10

ER -

Genetic polymorphisms in 15q25 and 19q13 loci, cotinine levels, and risk of lung cancer in EPIC

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