Polymorphisms in inflammatory pathway genes, host factors and lung cancer risk in Chinese female never-smokers.
Inflammation appears to be important in lung carcinogenesis among smokers, but its role among never-smokers is not well established. We hypothesized that inflammatory medical conditions and gene polymorphisms interact to increase lung cancer risk in never-smokers. We interviewed 433 Singaporean female never-smoker lung cancer patients and 1375 hospital controls, and evaluated six polymorphisms in the interleukin 1-β, interleukin 6 (IL6), cyclooxygenase-2, peroxisome proliferator-activated receptor-γ and interleukin 1-β receptor antagonist (IL1RN) genes. Tuberculosis was associated with a non-significant elevated risk of lung cancer [odds ratio (OR) 1.58, 95% confidence interval (CI) 0.95-2.62]. There was no effect of asthma, atopy or chronic productive cough individually. However, the presence of one or more of these conditions (asthma, cough or atopy) increased risk (OR 2.24, 95%CI 1.15-4.38) in individuals possessing the T/T genotype at interleukin 1-β -31T/C, but not in those possessing the C/T (OR 0.87, 95%CI 0.51-1.57) or C/C genotypes (OR 0.58, 95%CI 0.27-1.27), and in individuals having the *2 variable number of tandem repeat allele of IL1RN [OR 5.09 (1.39-18.67)], but not in those without (OR 0.93, 95%CI 0.63-1.35). The IL6-634 G allele increased the risk of lung cancer (OR 1.44, 95%CI 1.07-1.94). Lung cancer risk also increased with the number of polymorphism sites where at least 1 'risk' allele was present [interleukin 1-β -31T/C (T allele), IL1RN (*2 allele) and IL6-634C/G (G allele)] among those with asthma, cough or atopy (Ptrend 0.001) but not in those without (Ptrend 0.47). Our results suggest that the effect of inflammatory medical conditions on lung cancer in never-smokers is modulated by host genetic susceptibility and will need to be confirmed in other studies conducted in similar populations.
Department of Epidemiology & Public Health National University of Singapore, and Department of Pathology, Tan Tock Seng Hospital, Singapore, Singapore. wei-yen_lim@nuhs.edu.sg
Wei-Yen
WY
Lim
Ying
Y
Chen
Safiyya Mohamed
SM
Ali
Khoon Leong
KL
Chuah
Philip
P
Eng
Swan Swan
SS
Leong
Elaine
E
Lim
Tow Keang
TK
Lim
Alan W K
AW
Ng
Wee Teng
WT
Poh
Augustine
A
Tee
Ming
M
Teh
Agus
A
Salim
Adeline
A
Seow
D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D002681:China; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein / Q000235:genetics; D053583:Interleukin-1beta / Q000235:genetics; D015850:Interleukin-6 / Q000235:genetics; D008175:Lung Neoplasms / Q000209:etiology* / Q000235:genetics; D008875:Middle Aged; D018598:Minisatellite Repeats; D020641:Polymorphism, Single Nucleotide; D012306:Risk
C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D053583:Interleukin-1beta; D015850:Interleukin-6