Complement C3 Genotype Variants and Risk of Lung Cancer Mortality

Inflammation and genetic susceptibility influence the risk of lung cancer. During recent years, the role of complement as a part of the humoral response has advanced from being considered complementary to being regarded as a central element in innate immunity. C3 complement allotypes F and S have been associated with a number of inflammatory diseases. The C3F allele frequency is approximately 20% in Caucasian populations and the C3S approximately 80%, resulting in the three predominant genotypes FF (4%), FS (32%), and SS (64%). To our knowledge, no studies have investigated if different C3 allotypes or genotypes predict the risk of lung cancer. We tested in a long-term followup of 3,197 men aged 53 to 74 years the hypothesis that risk of lung cancer would depend on C3 complement genotypes. During 16 years, 160 subjects (5.0%) died from lung cancer, 68 men (6.1%) among complement C3 genotypes FS/FF, and 92 men (4.4%) among genotype SS; age-adjusted hazard ratio with 95%CI (HR) was 1.42 (1.04–1.94) and strongest, 2.71 (1.34–5.45), among the oldest fifth. C3 complement genotype variants were significantly associated with lung cancer mortality.