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Background  Education inequalities in cancer incidence have long been noted. It is not clear, however, whether such inequalities persist in the United States, especially for less common malignancies and after adjustment for individual risk factors.    Methodology/Principal Findings  Within the NIH–AARP Diet and Health Study, we examined the association between education and the risk of developing cancers in a prospective cohort of 498 455 participants who were 50–71 year old and without cancer at enrollment in 1995/96. During a maximum 8.2 years of follow–up we identified 40 443 cancers in men and 18 367 in women. In age-adjusted models, the least educated men (<high school), compared to those with the most education (post–graduate), had increased risks of developing cancers of the esophagus (RR: 2.64, 95%CI:1.86–3.75), head and neck (1.98, 1.54–2.54), stomach (2.32, 1.68–3.18), colon (1.31, 1.12–1. 53), rectum (1.68, 1.32–2.13), liver (1.90, 1.22–2.95), lung (3.67, 3.25–4.15), pleura (4.01, 1.91–8.42), bladder (1.56,1.33–1.83) and combined smoking–related cancers (2.41, 2.22–2.62). In contrast, lower education level was associated with a decreased risk of melanoma of the skin (0.43, 0.35–0.54) and local prostate cancers (0.79, 0.74–0.85). Women with the least education had increased risks of colon (1.60, 1.24–2.05), lung (2.14, 1.79–2.56), kidney (1.68, 1.12–2.54) and combined smoking–related cancers (1.66, 1.43–1.92) but a lower risk of melanoma of the skin (0.33, 0.22–0.51), endometrial (0.67, 0.51–0.89) and invasive breast cancers (0.72, 0.61–0.84). Adjustment for smoking and other risk factors did not eliminate these associations, except those for cancers of the head and neck, colon, and liver in men and kidney in women.    Conclusions/Significance  We found a higher risk of malignant disease, particularly smoking– related cancers, among those in the lowest educational attainment category. Only some of the educational gradient is attributable to smoking. The persistence of substantial education inequalities in cancer incidence poses a challenge for etiologic research and public health policy.

Education and Risk of Cancer in a Large Cohort of Men and Women in the United States