Allele 2 of the interleukin-1 receptor antagonist gene (IL1RN*2) is associated with a decreased risk of primary lung cancer.
IL-1 receptor antagonist (IL-1ra), a structural variant of IL-1, binds to the same IL-1 receptor and acts as a competitive inhibitor of IL-1 bioactivity. IL-1ra protein has been widely investigated and found to be associated with different human malignancies. In the second intron of the IL-1RN gene, there is a functional polymorphism of a variable number of tandem repeats (VNTR), which is characterized as having an importance role in regulating the serum IL-1ra levels, human immune response and cancer risk. We genotyped this VNTR of IL-1RN in a case-control study of 885 histologically confirmed lung cancer patients and 1024 cancer-free controls frequency-matched to the cases on age and sex in a Chinese population to evaluate the association of this variant and lung cancer risk. We found that the presence of the allele 2 of IL-1RN (IL-RN*2) was associated with a 32% significantly decreased risk of lung cancer (adjusted OR, 0.68; 95% CI, 0.52-0.89). Stratified analyses revealed that the reduced risks associated with the genotypes with IL-RN*2allele (I/II and II/II) were more evident in non-smokers (adjusted OR, 0.53; 95% CI, 0.35-0.79) and in subjects with squamous cell carcinoma (adjusted OR, 0.49; 95% CI, 0.31-0.76). These findings support our priori hypothesis that the IL1RN*2 allele may contribute to lung cancer risk in the Chinese population. More functional data for this IL1RN polymorphism are warranted to explore its role in lung carcinogenesis.
Hu
Zhibin
Z
Department of Epidemiology and Biostatistics, Nanjing Medical University School of Public Health, 140 Hanzhong Rd, Nanjing 210029, China.
Shao
Minhua
M
Chen
Yijiang
Y
Zhou
Jiannong
J
Qian
Ji
J
Xu
Lin
L
Ma
Hongxia
H
Wang
Xinru
X
Xu
Yaochu
Y
Lu
Daru
D
Shen
Hongbing
H
D000230:Adenocarcinoma / Q000235:genetics*; D000368:Aged; D018287:Carcinoma, Large Cell / Q000235:genetics*; D018288:Carcinoma, Small Cell / Q000235:genetics*; D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D016022:Case-Control Studies; D002681:China; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein; D007438:Introns; D008175:Lung Neoplasms / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D018598:Minisatellite Repeats; D011110:Polymorphism, Genetic; D012307:Risk Factors; D012795:Sialoglycoproteins / Q000235:genetics*; D012907:Smoking / Q000235:genetics
C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D012795:Sialoglycoproteins