Class A Scavenger Receptor Deficiency Exacerbates Lung Tumorigenesis by Cultivating a Procarcinogenic Microenvironment in Humans and Mice

Rationale: Genetic alterations on 8p22 have been implicated in multiple cancers, including lung cancer. In this region, genetic variants of the class A scavenger receptor (SR-A) gene have been associated with prostate cancer risk and have been highlighted as a potential susceptibility gene of cancer.Objectives: To determine whether common polymorphisms in the SR-A gene are associated with human lung cancer risk and to clarify the role of SR-A in lung carcinogenesis.Methods: The relationship of three potentially functional polymorphisms (T-365C, T+25C, and Ala275Pro) in the SR-A gene with lung cancer risk was evaluated in 1287 lung cancer case subjects and 1261 control subjects from the Chinese population. At the same time, SR-A null mice were used to investigate its role in lung cancer development.Measurements and Main Results: The T+25C polymorphism was independently associated with lung cancer risk and significantly correlated with decreased expression of SR-A. The decreased SR-A expression was also fou...