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: Zhi Zhang, Dianke Yu, Juxiang Yuan, Yongli Guo, Hongge Wang, Xuemei Zhang
• Journal: Cancer epidemiology (Cancer Epidemiol) Vol. 36 Issue 2 Pg. e111-5 (Apr 2012) ISSN: 1877-783X [Electronic] Netherlands
• PMID: 22197220 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Elsevier Ltd. All rights reserved.

Chemical References

• Complement Factor H

Topics

• Aged
• Asian People
• Complement Factor H (genetics)
• Female
• Genetic Predisposition to Disease
• Genotype
• Humans
• Lung Neoplasms (etiology, genetics)
• Male
• Middle Aged
• Polymorphism, Single Nucleotide
• Smoking (adverse effects, genetics)