BACKGROUND: Genome-wide association studies have identified 15q25 and 5p15 as lung cancer risk chromosomal regions in whites. The genetic structures of these loci differ between Asians and whites, however, indicating the need for additional studies in Asian populations. To examine the impact of 15p25 and 5p15 on lung cancer risk and smoking intensity, we conducted a case-control study in Japanese population. We also examined whether these loci modify the effect of smoking behavior on lung cancer risk. METHODS: Subjects were 716 Japanese patients with lung cancer and 716 controls. Associations were examined by logistic regression models with adjustment for potential confounders. RESULTS: We found that the variants of rs12914385 and rs931794 on 15q25 modified the effect of cumulative tobacco smoking on lung cancer risk but that these two loci showed no statistically significant main effects on lung cancer risk. Compared with never smoking without the risk allele of rs931794, odds ratio for heavy smoking without the risk allele was 4.03 (95% confidence interval: 2.45-6.62) and that with the risk allele was 8.09 (5.09-12.9), and the joint effect of rs931734 and cumulative tobacco consumption was statistically significant (pinteraction < 0.001). A similar impact was observed with rs12914385 at chromosome 15q25 (pinteraction = 0.021). Associations for the TERT-CLPM1L locus on 5p15 with lung cancer risk in Japanese patients were of a similar magnitude to those in whites. CONCLUSIONS: These results support the contribution of 15q25 and 5p15 to lung cancer and indicate that the 15q25 region modifies the well-established effect of smoking on the risk of lung cancer in a Japanese population.
BACKGROUND: Genome-wide association studies have identified 15q25 and 5p15 as lung cancer risk chromosomal regions in whites. The genetic structures of these loci differ between Asians and whites, however, indicating the need for additional studies in Asian populations. To examine the impact of 15p25 and 5p15 on lung cancer risk and smoking intensity, we conducted a case-control study in Japanese population. We also examined whether these loci modify the effect of smoking behavior on lung cancer risk. METHODS: Subjects were 716 Japanese patients with lung cancer and 716 controls. Associations were examined by logistic regression models with adjustment for potential confounders. RESULTS: We found that the variants of rs12914385 and rs931794 on 15q25 modified the effect of cumulative tobacco smoking on lung cancer risk but that these two loci showed no statistically significant main effects on lung cancer risk. Compared with never smoking without the risk allele of rs931794, odds ratio for heavy smoking without the risk allele was 4.03 (95% confidence interval: 2.45-6.62) and that with the risk allele was 8.09 (5.09-12.9), and the joint effect of rs931734 and cumulative tobacco consumption was statistically significant (pinteraction < 0.001). A similar impact was observed with rs12914385 at chromosome 15q25 (pinteraction = 0.021). Associations for the TERT-CLPM1L locus on 5p15 with lung cancer risk in Japanese patients were of a similar magnitude to those in whites. CONCLUSIONS: These results support the contribution of 15q25 and 5p15 to lung cancer and indicate that the 15q25 region modifies the well-established effect of smoking on the risk of lung cancer in a Japanese population.
Authors: Darren R Brenner; Christopher I Amos; Yonathan Brhane; Maria N Timofeeva; Neil Caporaso; Yufei Wang; David C Christiani; Heike Bickeböller; Ping Yang; Demetrius Albanes; Victoria L Stevens; Susan Gapstur; James McKay; Paolo Boffetta; David Zaridze; Neonilia Szeszenia-Dabrowska; Jolanta Lissowska; Peter Rudnai; Eleonora Fabianova; Dana Mates; Vladimir Bencko; Lenka Foretova; Vladimir Janout; Hans E Krokan; Frank Skorpen; Maiken E Gabrielsen; Lars Vatten; Inger Njølstad; Chu Chen; Gary Goodman; Mark Lathrop; Tõnu Vooder; Kristjan Välk; Mari Nelis; Andres Metspalu; Peter Broderick; Timothy Eisen; Xifeng Wu; Di Zhang; Wei Chen; Margaret R Spitz; Yongyue Wei; Li Su; Dong Xie; Jun She; Keitaro Matsuo; Fumihiko Matsuda; Hidemi Ito; Angela Risch; Joachim Heinrich; Albert Rosenberger; Thomas Muley; Hendrik Dienemann; John K Field; Olaide Raji; Ying Chen; John Gosney; Triantafillos Liloglou; Michael P A Davies; Michael Marcus; John McLaughlin; Irene Orlow; Younghun Han; Yafang Li; Xuchen Zong; Mattias Johansson; Geoffrey Liu; Shelley S Tworoger; Loic Le Marchand; Brian E Henderson; Lynne R Wilkens; Juncheng Dai; Hongbing Shen; Richard S Houlston; Maria T Landi; Paul Brennan; Rayjean J Hung Journal: Carcinogenesis Date: 2015-09-10 Impact factor: 4.944