title: Cigarette smoking strongly modifies the association of complement factor H variant and the risk of lung cancer.
abstract: The complement system is an important immunosurveillance mechanism against tumors, and complement factor H (CFH) is a key regulator for activation of the complement system. Expression of complement factor H has been demonstrated in cell lines from several malignancies. In this study we examined the contribution of the single-nucleotide polymorphism (SNP) Try402His (Y402H) (rs1061170) in the CFH gene to the risk of lung cancer in a case-control study with 1000 cases and 1000 controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were computed by logistic regression. The frequencies for CFH Y402H genotypes among the cases were statistically significantly different from those among controls (χ(2)=8.66, P=0.003), with 402His/His or 402His/Try genotypes being over-represented among patients compared with controls (13.6% versus 9.4%, P<0.004). A multivariate regression analysis showed that a significantly increased risk of lung cancer for the 402His/His or 402His/Try carriers with OR (95% CI), 1.50 (1.12-2.00). When stratified by smoking status, the elevated risk of the cancer associated with variant CFH genotypes was observed among smokers, but not among non-smokers. When analyzed with cumulative smoking dose (pack-years), a super-multiplicative interaction was observed at different smoking levels. Among carriers with the 402Tyr/His or His/His genotype, the ORs of developing lung cancer for smoking<16, 16-28, or >28 pack-years were 0.98 (0.49-1.94), 2.36 (1.14-4.90), and 6.39 (3.49-11.68), respectively. These findings suggest that CFH Y402H polymorphism may interact with cigarette smoking to effect the development of lung cancer in the Chinese population.
authors.affiliation: Department of Cancer Chemotherapy and Radiology, Tangshan Gongren Hospital, China.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Zhang
authors.forename: Dianke
authors.initials: D
authors.lastname: Yu
authors.forename: Juxiang
authors.initials: J
authors.lastname: Yuan
authors.forename: Yongli
authors.initials: Y
authors.lastname: Guo
authors.forename: Hongge
authors.initials: H
authors.lastname: Wang
authors.forename: Xuemei
authors.initials: X
authors.lastname: Zhang
mesh_terms: D000368:Aged; D044466:Asian People; D017242:Complement Factor H / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008175:Lung Neoplasms / Q000209:etiology* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012907:Smoking / Q000009:adverse effects* / Q000235:genetics
chemical_list: D017242:Complement Factor H