Rare SP-A alleles and the SP-A1-6A⁴ allele associate with risk for lung carcinoma

Next to cigarette smoking, genetic factors may contribute to lung cancer risk. Pulmonary surfactant components may mediate response to inhaled carcinogenic substances and/or play a role in lung function and inflammation. We studied associations between surfactant protein (SP) genetic variants and risk in lung cancer subgroups. Samples (n = 308) were genotyped for SP-A1, -A2, -B, and -D marker alleles. These included 99 patients with small cell lung carcinoma (SCLC, n = 31), or non-SCLC (NSCLC, n = 68) consisting of squamous cell carcinoma (SCC, n = 35), and adenocarcinoma (AC) (n = 23); controls (n = 99) matched by age, sex, and smoking status (clinical control) to SCLC and NSCLC; and 110 healthy individuals (population control). We found (a) no significant marker associations with SCLC, (b) rare SP-A2 (1A⁹) and SP-A1 (6A¹¹) alleles associate with NSCLC risk when compared with population control, (c) the same alleles (1A⁹, 6A¹¹) associate with risk for AC when compared with population (6A¹¹) or clinical control (1A⁹), and (d) the SP-A1-6A⁴ allele (found in approximately 10% of the population) associates with SCC, when compared with population or clinical control. A correlation between SP-A variants and lung cancer susceptibility appears to exist, indicating that SP-A alleles may be useful markers of lung cancer risk.