The common use of wok cooking in China might be an important but controllable risk factor in the etiology of lung cancer. In the United States, where cooking oils are usually refined for purity, additional studies should be conducted to further quantify the potential risks of such methods of cooking.

Nitric oxide (NO . ), an important signaling molecule and a component of inflammatory response, is involved in tumorigenesis. However, the quantity of NO. and the cellular microenvironment influences the role of NO . in tumor development. We used a genetic strategy to test the hypothesis that an inflammatory microenvironment with an enhanced level of NO . accelerates spontaneous tumor development. C. parvuminduced inflammation and increased NO . synthase-2 (NOS2) expression coincided with accelerated spontaneous tumor development, mostly lymphomas, in p53À/ÀNOS2+/+ C57BL6 mice when compared with the controls (P = 0.001). However, p53À/ÀNOS2À/À mice did not show any difference in tumor latency between C. parvum-treated and control groups. In C. parvum-treated p53À/ÀNOS2+/+ mice, tumor development was preceded by a higher expression of NOS2 and phosphorylated Akt-Ser 473

Accumulating evidence suggests a role for inflammation in the development and progression of cancer. Our group recently identified a cytokine gene signature in lung tissue associated with lung cancer prognosis. Therefore, we hypothesized that concentrations of circulating cytokines in serum may be associated with lung cancer survival. Ten serum cytokines, namely, interleukin (IL)-1B, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12, granulocyte macrophage colony-stimulating factor, interferon (IFN)-;, and tumor necrosis factor-A, were assessed in 353 non -small cell lung cancer cases from a case-control study of lung cancer in the greater Baltimore, Maryland area. Cytokines were measured using an ultrasensitive electrochemiluminescence immunoassay. IL-6 serum concentrations (z4.0 pg/mL) were associated with significantly poorer survival in both African Americans [hazard ratio (HR), 2.71; 95% confidence interval (CI), 1.26-5.80] and Caucasians (HR, 1.71; 95% CI, 1.22-2.40). IL-10 (HR, 2.62; 95% CI, 1.33-5.15) and IL-12 (HR, 1.98; 95% CI, 1.14-3.44) were associated with lung cancer survival only in African Americans. Some evidence for an association of tumor necrosis factor-A levels with survival in Caucasians was observed, although these results were not significant. These hypothesis-generating findings indicate that selected serum cytokine concentrations are associated with lung cancer survival, and indicate that further research is warranted to better understand the mechanistic underpinnings of these associations. (Cancer Epidemiol Biomarkers Prev 2009;18(1):215 -22)

Inflammation influences the development of cancer. The nitric oxide synthase (NOS2) is induced by inflammatory cytokines, e.g., tumor necrosis factor ␣ and interleukin 1␤, and produces nitric oxide (NO ⅐ ), a critical mediator of the inflammatory response. Because p53 governs NO ⅐ production by transcriptionally transrepressing NOS2, we used a genetic strategy to determine whether NO ⅐ and p53 cooperatively regulate tumorigenesis. Lymphomas developed more rapidly in p53؊/؊NOS2؊/؊ or p53؊/؊NOS2؉/؊ mice than in p53؊/؊NOS2؉/؉ mice that were crossbred into a >95% C57BL6 background and maintained in a pathogenfree condition. Likewise, sarcomas and lymphomas developed faster in p53؉/؊NOS2؊/؊ or p53؉/؊NOS2؉/؊ than in p53؉/؊NOS2؉/؉ mice. When compared with the double knockout mice, p53؊/؊NOS2؉/؉ mice showed a higher apoptotic index and a decreased proliferation index with an increased expression of death receptor ligands, CD95-L and tumor necrosis factor-related apoptosis-inducing ligand, and the cell cycle checkpoint protein, p21 waf1 , in the spleen and thymus before tumor development. Furthermore, mice deficient in both p53 and NOS2 produced a high level of anti-inflammatory interleukin 10 when compared with p53-deficient mice. These studies provide genetic and mechanistic evidence that NO ⅐ can suppress tumorigenesis.