Polymorphisms in innate immunity genes and lung cancer risk in Xuanwei, China.

Abstract

The high incidence of lung cancer in Xuanwei County, China has been attributed to exposure to indoor smoky coal emissions that contain polycyclic aromatic hydrocarbons (PAHs). The inflammatory response induced by coal smoke components may promote lung tumor development. We studied the association between single nucleotide polymorphisms (SNPs) in genes involved in innate immunity and lung cancer risk in a population-based case-control study (122 cases and 122 controls) in Xuanwei. A total of 1,360 tag SNPs in 149 gene regions were included in the analysis. FCER2 rs7249320 was the most significant SNP (OR: 0.30; 95% CI: 0.16-0.55; P: 0.0001; false discovery rate value, 0.13) for variant carriers. The gene regions ALOX12B/ALOX15B and KLK2 were associated with increased lung cancer risk globally (false discovery rate value <0.15). In addition, there were positive interactions between KLK15 rs3745523 and smoky coal use (OR: 9.40; P-interaction = 0.07) and between FCER2 rs7249320 and KLK2 rs2739476 (OR: 10.77; P-interaction = 0.003). Our results suggest that genetic polymorphisms in innate immunity genes may play a role in the genesis of lung cancer caused by PAH-containing coal smoke. Integrin/receptor and complement pathways as well as IgE regulation are particularly noteworthy.

• Authors: Min Shen, Roel Vermeulen, Preetha Rajaraman, Idan Menashe, Xingzhou He, Robert S Chapman, Meredith Yeager, Gilles Thomas, Laurie Burdett, Amy Hutchinson, Jeff Yuenger, Stephen Chanock, Qing Lan
• Journal: Environmental and molecular mutagenesis (Environ Mol Mutagen) Vol. 50 Issue 4 Pg. 285-90 (May 2009) ISSN: 1098-2280 [Electronic] United States
• PMID: 19170196 (Publication Type: Journal Article, Research Support, N.I.H., Intramural, Research Support, Non-U.S. Gov't)

Chemical References

• Coal
• DNA, Neoplasm
• Smoke
• Complement System Proteins
• ALOX12B protein, human
• Arachidonate 12-Lipoxygenase
• KLK15 protein, human
• Kallikreins
• Tissue Kallikreins

Topics

• Arachidonate 12-Lipoxygenase (genetics)
• Case-Control Studies
• China (epidemiology)
• Coal (adverse effects)
• Complement System Proteins (genetics)
• DNA, Neoplasm (genetics, isolation & purification)
• Female
• Genotype
• Homozygote
• Humans
• Immunity, Innate (genetics)
• Incidence
• Kallikreins (genetics)
• Lung Neoplasms (epidemiology, genetics, immunology)
• Male
• Middle Aged
• Polymorphism, Genetic
• Polymorphism, Single Nucleotide
• Risk Assessment
• Smoke (adverse effects)
• Smoking (adverse effects)
• Tissue Kallikreins (genetics)