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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: BACKGROUND, OBJECTIVE, METHODS, RESULTS. Meshes: Animals, Asian Continental Ancestry Group, Carcinoma, Lewis Lung, Case-Control Studies, China, Female, Genetic Predisposition to Disease, Humans, Lung Neoplasms, Mice, Mice, Knockout, Polymorphism, Genetic, Scavenger Receptors, Class A.
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Does class A scavenger receptor deficiency exacerbate lung tumorigenesis by cultivating a procarcinogenic microenvironment in humans and mice? Context: 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. 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. 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. 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 found in tumor tissues as compared with normal tissues. Depletion of SR-A boosted the growth and angiogenesis of implanted Lewis lung carcinoma in mice. The cancer-suppressing capability of SR-A was attributable to its expression in bone marrow-derived cells as evidenced by bone marrow transplantation. Further analysis revealed augmented expression of proangiogenic factors including matrix metalloproteinase-9 (MMP9) in SR-A-deficient mice, indicative of a more procarcinogenic microenvironment. Last, zoledronate, an MMP9 inhibitor, abrogated acceleration of tumor growth conferred by SR-A loss-of-function.
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Evidence from the population study and mouse model strongly indicates that SR-A may function as a tumor modulator to inhibit lung cancer growth through affecting the tumor microenvironment. Final Decision: yes