Single-nucleotide polymorphisms (5p15.33, 15q25.1, 6p22.1, 6q27 and 7p15.3) and lung cancer survival in the European Prospective Investigation into Cancer and Nutrition (EPIC)

Wei Wei Xun, Paul Brennan, Anne Tjonneland, Ulla Vogel, Kim Overvad, Rudolf Kaaks, Federico Canzian, Heiner Boeing, Antonia Trichopoulou, Erifili Oustoglou, Zoi Giotaki, Mattias Johansson, Domenico Palli, Claudia Agnoli, Rosario Tumino, Carlotta Sacerdote, Salvatore Panico, H. Bas Bueno-De-Mesquita, Petra H M Peeters, Eiliv LundMerethe Kumle, Laudina Rodríguez, Antonio Agudo, Maria José Sánchez, Larraitz Arriola, María Dolores Chirlaque, Aurelio Barricarte, Göran Hallmans, Torgny Rasmuson, Kay Tee Khaw, Nicholas Wareham, Tim Key, Elio Riboli, Paolo Vineis

Research output: Contribution to journalArticle

Abstract

The single-nucleotide polymorphisms (SNPs) rs402710 (5p15.33), rs16969968 and rs8034191 (15q25.1) have been consistently identified by genome-wide association studies (GWAS) as significant predictors of lung cancer risk, while rs4324798 (6p22.1) was previously found to influence survival time in small-cell lung cancer (SCLC) patients. Using the same population of one of the original GWAS, we investigated whether the selected SNPs and 31 others (also identified in GWAS) influence survival time, assuming an additive model. The effect of each polymorphism on all cause survival was estimated in 1094 lung cancer patients, and lung cancer-specific survival in 763 patients, using Cox regression adjusted for a priori confounders and competing causes of death where appropriate. Overall, after 1558 person-years of post-diagnostic follow-up, 874 deaths occurred from all causes, including 690 from lung cancer. In the lung cancer-specific survival analysis (1102 person-years), only rs7452888 (6q27) and rs2710994 (7p15.3) modified survival, with adjusted hazard ratios of 1.19 (P = 0.009) and 1.32 (P = 0.011) respectively, taking competing risks into account. Some weak associations were identified in subgroup analysis for rs16969968 and rs8034191 (15q25.1) and rs4324798 (6p22.1) and survival in never-smokers, as well as for rs402710 in current smokers and SCLC patients. In conclusion, rs402710 (5p15.33), rs16969968 and rs8034191 (both 15q25.1) and rs4324798 (6p22.1) were found to be unrelated to survival times in this large cohort of lung cancer patients, regardless of whether the cause of death was from lung cancer or not. However, rs7452888 (6q27) was identified as a possible candidate SNP to influence lung cancer survival, while stratified analysis hinted at a possible role for rs8034191, rs16969968 (15q25.1) and rs4324798 (6p22.1) in influencing survival time in lung cancer patients who were never-smokers, based on a small sample.

Original languageEnglish
Pages (from-to)657-666
Number of pages10
JournalMutagenesis
Volume26
Issue number5
DOIs
Publication statusPublished - Sep 2011

Fingerprint

Nutrition
Polymorphism
Single Nucleotide Polymorphism
Lung Neoplasms
Nucleotides
Survival
Genes
Neoplasms
Genome-Wide Association Study
Small Cell Lung Carcinoma
Hazards
Cells
Cause of Death
Survival Analysis
Risk-Taking

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)
  • Toxicology
  • Health, Toxicology and Mutagenesis

Cite this

Single-nucleotide polymorphisms (5p15.33, 15q25.1, 6p22.1, 6q27 and 7p15.3) and lung cancer survival in the European Prospective Investigation into Cancer and Nutrition (EPIC). / Xun, Wei Wei; Brennan, Paul; Tjonneland, Anne; Vogel, Ulla; Overvad, Kim; Kaaks, Rudolf; Canzian, Federico; Boeing, Heiner; Trichopoulou, Antonia; Oustoglou, Erifili; Giotaki, Zoi; Johansson, Mattias; Palli, Domenico; Agnoli, Claudia; Tumino, Rosario; Sacerdote, Carlotta; Panico, Salvatore; Bueno-De-Mesquita, H. Bas; Peeters, Petra H M; Lund, Eiliv; Kumle, Merethe; Rodríguez, Laudina; Agudo, Antonio; Sánchez, Maria José; Arriola, Larraitz; Chirlaque, María Dolores; Barricarte, Aurelio; Hallmans, Göran; Rasmuson, Torgny; Khaw, Kay Tee; Wareham, Nicholas; Key, Tim; Riboli, Elio; Vineis, Paolo.

In: Mutagenesis, Vol. 26, No. 5, 09.2011, p. 657-666.

Research output: Contribution to journalArticle

Xun, WW, Brennan, P, Tjonneland, A, Vogel, U, Overvad, K, Kaaks, R, Canzian, F, Boeing, H, Trichopoulou, A, Oustoglou, E, Giotaki, Z, Johansson, M, Palli, D, Agnoli, C, Tumino, R, Sacerdote, C, Panico, S, Bueno-De-Mesquita, HB, Peeters, PHM, Lund, E, Kumle, M, Rodríguez, L, Agudo, A, Sánchez, MJ, Arriola, L, Chirlaque, MD, Barricarte, A, Hallmans, G, Rasmuson, T, Khaw, KT, Wareham, N, Key, T, Riboli, E & Vineis, P 2011, 'Single-nucleotide polymorphisms (5p15.33, 15q25.1, 6p22.1, 6q27 and 7p15.3) and lung cancer survival in the European Prospective Investigation into Cancer and Nutrition (EPIC)', Mutagenesis, vol. 26, no. 5, pp. 657-666. https://doi.org/10.1093/mutage/ger030
Xun, Wei Wei ; Brennan, Paul ; Tjonneland, Anne ; Vogel, Ulla ; Overvad, Kim ; Kaaks, Rudolf ; Canzian, Federico ; Boeing, Heiner ; Trichopoulou, Antonia ; Oustoglou, Erifili ; Giotaki, Zoi ; Johansson, Mattias ; Palli, Domenico ; Agnoli, Claudia ; Tumino, Rosario ; Sacerdote, Carlotta ; Panico, Salvatore ; Bueno-De-Mesquita, H. Bas ; Peeters, Petra H M ; Lund, Eiliv ; Kumle, Merethe ; Rodríguez, Laudina ; Agudo, Antonio ; Sánchez, Maria José ; Arriola, Larraitz ; Chirlaque, María Dolores ; Barricarte, Aurelio ; Hallmans, Göran ; Rasmuson, Torgny ; Khaw, Kay Tee ; Wareham, Nicholas ; Key, Tim ; Riboli, Elio ; Vineis, Paolo. / Single-nucleotide polymorphisms (5p15.33, 15q25.1, 6p22.1, 6q27 and 7p15.3) and lung cancer survival in the European Prospective Investigation into Cancer and Nutrition (EPIC). In: Mutagenesis. 2011 ; Vol. 26, No. 5. pp. 657-666.
@article{4d569a0bf9f6452c9674c8b1f07067ae,
title = "Single-nucleotide polymorphisms (5p15.33, 15q25.1, 6p22.1, 6q27 and 7p15.3) and lung cancer survival in the European Prospective Investigation into Cancer and Nutrition (EPIC)",
abstract = "The single-nucleotide polymorphisms (SNPs) rs402710 (5p15.33), rs16969968 and rs8034191 (15q25.1) have been consistently identified by genome-wide association studies (GWAS) as significant predictors of lung cancer risk, while rs4324798 (6p22.1) was previously found to influence survival time in small-cell lung cancer (SCLC) patients. Using the same population of one of the original GWAS, we investigated whether the selected SNPs and 31 others (also identified in GWAS) influence survival time, assuming an additive model. The effect of each polymorphism on all cause survival was estimated in 1094 lung cancer patients, and lung cancer-specific survival in 763 patients, using Cox regression adjusted for a priori confounders and competing causes of death where appropriate. Overall, after 1558 person-years of post-diagnostic follow-up, 874 deaths occurred from all causes, including 690 from lung cancer. In the lung cancer-specific survival analysis (1102 person-years), only rs7452888 (6q27) and rs2710994 (7p15.3) modified survival, with adjusted hazard ratios of 1.19 (P = 0.009) and 1.32 (P = 0.011) respectively, taking competing risks into account. Some weak associations were identified in subgroup analysis for rs16969968 and rs8034191 (15q25.1) and rs4324798 (6p22.1) and survival in never-smokers, as well as for rs402710 in current smokers and SCLC patients. In conclusion, rs402710 (5p15.33), rs16969968 and rs8034191 (both 15q25.1) and rs4324798 (6p22.1) were found to be unrelated to survival times in this large cohort of lung cancer patients, regardless of whether the cause of death was from lung cancer or not. However, rs7452888 (6q27) was identified as a possible candidate SNP to influence lung cancer survival, while stratified analysis hinted at a possible role for rs8034191, rs16969968 (15q25.1) and rs4324798 (6p22.1) in influencing survival time in lung cancer patients who were never-smokers, based on a small sample.",
author = "Xun, {Wei Wei} and Paul Brennan and Anne Tjonneland and Ulla Vogel and Kim Overvad and Rudolf Kaaks and Federico Canzian and Heiner Boeing and Antonia Trichopoulou and Erifili Oustoglou and Zoi Giotaki and Mattias Johansson and Domenico Palli and Claudia Agnoli and Rosario Tumino and Carlotta Sacerdote and Salvatore Panico and Bueno-De-Mesquita, {H. Bas} and Peeters, {Petra H M} and Eiliv Lund and Merethe Kumle and Laudina Rodr{\'i}guez and Antonio Agudo and S{\'a}nchez, {Maria Jos{\'e}} and Larraitz Arriola and Chirlaque, {Mar{\'i}a Dolores} and Aurelio Barricarte and G{\"o}ran Hallmans and Torgny Rasmuson and Khaw, {Kay Tee} and Nicholas Wareham and Tim Key and Elio Riboli and Paolo Vineis",
year = "2011",
month = "9",
doi = "10.1093/mutage/ger030",
language = "English",
volume = "26",
pages = "657--666",
journal = "Mutagenesis",
issn = "0267-8357",
publisher = "Oxford University Press",
number = "5",

}

TY - JOUR

T1 - Single-nucleotide polymorphisms (5p15.33, 15q25.1, 6p22.1, 6q27 and 7p15.3) and lung cancer survival in the European Prospective Investigation into Cancer and Nutrition (EPIC)

AU - Xun, Wei Wei

AU - Brennan, Paul

AU - Tjonneland, Anne

AU - Vogel, Ulla

AU - Overvad, Kim

AU - Kaaks, Rudolf

AU - Canzian, Federico

AU - Boeing, Heiner

AU - Trichopoulou, Antonia

AU - Oustoglou, Erifili

AU - Giotaki, Zoi

AU - Johansson, Mattias

AU - Palli, Domenico

AU - Agnoli, Claudia

AU - Tumino, Rosario

AU - Sacerdote, Carlotta

AU - Panico, Salvatore

AU - Bueno-De-Mesquita, H. Bas

AU - Peeters, Petra H M

AU - Lund, Eiliv

AU - Kumle, Merethe

AU - Rodríguez, Laudina

AU - Agudo, Antonio

AU - Sánchez, Maria José

AU - Arriola, Larraitz

AU - Chirlaque, María Dolores

AU - Barricarte, Aurelio

AU - Hallmans, Göran

AU - Rasmuson, Torgny

AU - Khaw, Kay Tee

AU - Wareham, Nicholas

AU - Key, Tim

AU - Riboli, Elio

AU - Vineis, Paolo

PY - 2011/9

Y1 - 2011/9

N2 - The single-nucleotide polymorphisms (SNPs) rs402710 (5p15.33), rs16969968 and rs8034191 (15q25.1) have been consistently identified by genome-wide association studies (GWAS) as significant predictors of lung cancer risk, while rs4324798 (6p22.1) was previously found to influence survival time in small-cell lung cancer (SCLC) patients. Using the same population of one of the original GWAS, we investigated whether the selected SNPs and 31 others (also identified in GWAS) influence survival time, assuming an additive model. The effect of each polymorphism on all cause survival was estimated in 1094 lung cancer patients, and lung cancer-specific survival in 763 patients, using Cox regression adjusted for a priori confounders and competing causes of death where appropriate. Overall, after 1558 person-years of post-diagnostic follow-up, 874 deaths occurred from all causes, including 690 from lung cancer. In the lung cancer-specific survival analysis (1102 person-years), only rs7452888 (6q27) and rs2710994 (7p15.3) modified survival, with adjusted hazard ratios of 1.19 (P = 0.009) and 1.32 (P = 0.011) respectively, taking competing risks into account. Some weak associations were identified in subgroup analysis for rs16969968 and rs8034191 (15q25.1) and rs4324798 (6p22.1) and survival in never-smokers, as well as for rs402710 in current smokers and SCLC patients. In conclusion, rs402710 (5p15.33), rs16969968 and rs8034191 (both 15q25.1) and rs4324798 (6p22.1) were found to be unrelated to survival times in this large cohort of lung cancer patients, regardless of whether the cause of death was from lung cancer or not. However, rs7452888 (6q27) was identified as a possible candidate SNP to influence lung cancer survival, while stratified analysis hinted at a possible role for rs8034191, rs16969968 (15q25.1) and rs4324798 (6p22.1) in influencing survival time in lung cancer patients who were never-smokers, based on a small sample.

AB - The single-nucleotide polymorphisms (SNPs) rs402710 (5p15.33), rs16969968 and rs8034191 (15q25.1) have been consistently identified by genome-wide association studies (GWAS) as significant predictors of lung cancer risk, while rs4324798 (6p22.1) was previously found to influence survival time in small-cell lung cancer (SCLC) patients. Using the same population of one of the original GWAS, we investigated whether the selected SNPs and 31 others (also identified in GWAS) influence survival time, assuming an additive model. The effect of each polymorphism on all cause survival was estimated in 1094 lung cancer patients, and lung cancer-specific survival in 763 patients, using Cox regression adjusted for a priori confounders and competing causes of death where appropriate. Overall, after 1558 person-years of post-diagnostic follow-up, 874 deaths occurred from all causes, including 690 from lung cancer. In the lung cancer-specific survival analysis (1102 person-years), only rs7452888 (6q27) and rs2710994 (7p15.3) modified survival, with adjusted hazard ratios of 1.19 (P = 0.009) and 1.32 (P = 0.011) respectively, taking competing risks into account. Some weak associations were identified in subgroup analysis for rs16969968 and rs8034191 (15q25.1) and rs4324798 (6p22.1) and survival in never-smokers, as well as for rs402710 in current smokers and SCLC patients. In conclusion, rs402710 (5p15.33), rs16969968 and rs8034191 (both 15q25.1) and rs4324798 (6p22.1) were found to be unrelated to survival times in this large cohort of lung cancer patients, regardless of whether the cause of death was from lung cancer or not. However, rs7452888 (6q27) was identified as a possible candidate SNP to influence lung cancer survival, while stratified analysis hinted at a possible role for rs8034191, rs16969968 (15q25.1) and rs4324798 (6p22.1) in influencing survival time in lung cancer patients who were never-smokers, based on a small sample.

UR - http://www.scopus.com/inward/record.url?scp=80052335498&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=80052335498&partnerID=8YFLogxK

U2 - 10.1093/mutage/ger030

DO - 10.1093/mutage/ger030

M3 - Article

C2 - 21750227

AN - SCOPUS:80052335498

VL - 26

SP - 657

EP - 666

JO - Mutagenesis

JF - Mutagenesis

SN - 0267-8357

IS - 5

ER -