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 journalArticlepeer-review

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

ASJC Scopus subject areas

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

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