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 language | English |
|---|---|
| Pages (from-to) | 657-666 |
| Number of pages | 10 |
| Journal | Mutagenesis |
| Volume | 26 |
| Issue number | 5 |
| DOIs | |
| Publication status | Published - Sep 2011 |
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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 journal › Article
}
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 -