Polymorphisms in innate immunity genes and lung cancer risk in Xuanwei, China.
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.
Shen
Min
M
Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, MSC 7240, 6120 Executive Blvd., Bethesda, Maryland 20892-7240, USA. shenmi@mail.nih.gov
Vermeulen
Roel
R
Rajaraman
Preetha
P
Menashe
Idan
I
He
Xingzhou
X
Chapman
Robert S
RS
Yeager
Meredith
M
Thomas
Gilles
G
Burdett
Laurie
L
Hutchinson
Amy
A
Yuenger
Jeff
J
Chanock
Stephen
S
Lan
Qing
Q
D001092:Arachidonate 12-Lipoxygenase / Q000235:genetics; D016022:Case-Control Studies; D002681:China / Q000453:epidemiology; D003031:Coal / Q000009:adverse effects; D003165:Complement System Proteins / Q000235:genetics; D004273:DNA, Neoplasm / Q000235:genetics / Q000302:isolation & purification; D005260:Female; D005838:Genotype; D006720:Homozygote; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics*; D015994:Incidence; D007610:Kallikreins / Q000235:genetics; D008175:Lung Neoplasms / Q000453:epidemiology* / Q000235:genetics* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D018570:Risk Assessment; D012906:Smoke / Q000009:adverse effects; D012907:Smoking / Q000009:adverse effects; D020840:Tissue Kallikreins / Q000235:genetics
D003031:Coal; D004273:DNA, Neoplasm; D012906:Smoke; D003165:Complement System Proteins; C514086:ALOX12B protein, human; D001092:Arachidonate 12-Lipoxygenase; C501608:KLK15 protein, human; D007610:Kallikreins; D020840:Tissue Kallikreins