Association between a Genome-Wide Association Study-Identified Locus and the Risk of Lung Cancer in Japanese Population.

Ito H, McKay JD, Hosono S, Hida T, Yatabe Y, Mitsudomi T, Brennan P, Tanaka H, Matsuo K.

Source

*Division of Epidemiology and Prevention, Aichi Cancer Center Research Institute, Nagoya, Japan †Genetic Cancer Susceptibility Group, International Agency for Research on Cancer, Nagoya, Japan ‡Departments of Thoracic Oncology, Aichi Cancer Center Hospital, Nagoya, Japan §Departments of Pathology and Molecular Diagnostics, Aichi Cancer Center Hospital, Nagoya, Japan ║Departments of Thoracic Surgery, Aichi Cancer Center Hospital, Nagoya, Japan ¶Genetic Epidemiology Group, International Agency for Research on Cancer, Nagoya, Japan #Department of Epidemiology, Nagoya University Graduate School of Medicine, Nagoya, Japan.

Abstract

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.