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.
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, St Mary's Campus, Norfolk Place, Paddington, LondonW2 1PG, UK.
authors.forename: Wei Wei
authors.initials: WW
authors.lastname: Xun
authors.forename: Paul
authors.initials: P
authors.lastname: Brennan
authors.forename: Anne
authors.initials: A
authors.lastname: Tjonneland
authors.forename: Ulla
authors.initials: U
authors.lastname: Vogel
authors.forename: Kim
authors.initials: K
authors.lastname: Overvad
authors.forename: Rudolf
authors.initials: R
authors.lastname: Kaaks
authors.forename: Federico
authors.initials: F
authors.lastname: Canzian
authors.forename: Heiner
authors.initials: H
authors.lastname: Boeing
authors.forename: Antonia
authors.initials: A
authors.lastname: Trichopoulou
authors.forename: Erifili
authors.initials: E
authors.lastname: Oustoglou
authors.forename: Zoi
authors.initials: Z
authors.lastname: Giotaki
authors.forename: Mattias
authors.initials: M
authors.lastname: Johansson
authors.forename: Domenico
authors.initials: D
authors.lastname: Palli
authors.forename: Claudia
authors.initials: C
authors.lastname: Agnoli
authors.forename: Rosario
authors.initials: R
authors.lastname: Tumino
authors.forename: Carlotta
authors.initials: C
authors.lastname: Sacerdote
authors.forename: Salvatore
authors.initials: S
authors.lastname: Panico
authors.forename: H Bas
authors.initials: HB
authors.lastname: Bueno-de-Mesquita
authors.forename: Petra H M
authors.initials: PH
authors.lastname: Peeters
authors.forename: Eiliv
authors.initials: E
authors.lastname: Lund
authors.forename: Merethe
authors.initials: M
authors.lastname: Kumle
authors.forename: Laudina
authors.initials: L
authors.lastname: Rodríguez
authors.forename: Antonio
authors.initials: A
authors.lastname: Agudo
authors.forename: Maria-José
authors.initials: MJ
authors.lastname: Sánchez
authors.forename: Larraitz
authors.initials: L
authors.lastname: Arriola
authors.forename: María-Dolores
authors.initials: MD
authors.lastname: Chirlaque
authors.forename: Aurelio
authors.initials: A
authors.lastname: Barricarte
authors.forename: Göran
authors.initials: G
authors.lastname: Hallmans
authors.forename: Torgny
authors.initials: T
authors.lastname: Rasmuson
authors.forename: Kay-Tee
authors.initials: KT
authors.lastname: Khaw
authors.forename: Nicholas
authors.initials: N
authors.lastname: Wareham
authors.forename: Tim
authors.initials: T
authors.lastname: Key
authors.forename: Elio
authors.initials: E
authors.lastname: Riboli
authors.forename: Paolo
authors.initials: P
authors.lastname: Vineis
mesh_terms: D000328:Adult; D000368:Aged; D002877:Chromosomes, Human; D002884:Chromosomes, Human, Pair 15; D002895:Chromosomes, Human, Pair 5; D002896:Chromosomes, Human, Pair 6; D002897:Chromosomes, Human, Pair 7; D005060:Europe; D005260:Female; D056426:Genetic Loci; D055106:Genome-Wide Association Study; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000401:mortality* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D012907:Smoking