Chronic inflammation contributes to the process of carcinogenesis, but few epidemiologic studies have examined associations with risk of lung cancer. Relationships between lung cancer risk and serum levels of both heat shock protein 70 (Hsp70) and high-sensitivity C-reactive protein (hsCRP) were investigated in a case-control study nested in the Japan Collaborative Cohort Study for Evaluation of Cancer Risk. Serum samples and lifestyle information were collected at baseline from 39,242 men and women between 1988 and 1990. Of these, 240 deaths from lung cancer were identified through 1999, and 569 controls were matched for sex, age, and study area. Serum levels were measured in 189 cases and 377 controls for Hsp70 and in 209 cases and 425 controls for hsCRP. Odds ratios (95% confidence intervals) across quartiles, adjusted for confounding factors, including smoking habits, were 0.83 (0.44-1.58), 1.41 (0.77-2.60), and 1.84 (0.92-3.71) for Hsp70 (Ptrend = 0.042) and 1.13 (0.67-1.91), 0.66 (0.38-1.16), and 1.19 (0.70-2.02) for hsCRP (P trend = 0.941). In males, odds ratios (95% confidence intervals) across quartiles were 1.30 (0.59-2.84), 1.74 (0.83-3.67), and 2.49 (1.06-5.85) for Hsp70 (Ptrend = 0.029). High levels of serum Hsp70 might thus be associated with increased risk of lung cancer among Japanese males, although further studies are needed to clarify associations between chronic inflammation and lung cancer. Copyright © 2006 American Association for Cancer Research.