Malignancies that occur before and after anal cancer: clues to their etiology

With the use of two different approaches to study multiple primaries in anal cancer patients, the authors sought clues to the etiology of anal cancer. Based on data from the Danish Cancer Registry for 1943-1989, previous cancers in 831 anal cancer patients were compared with cancers in 12,376 matched population controls, and subsequent cancers in 955 anal cancer patients were compared with expected numbers based on population rates. Overall, previous cancers were in excess among anal cancer patients (odds ratio (OR) = 1.7, 95% confidence interval (CI) 1.3-2.1). Elevated risks were observed especially for the vulva/vagina (OR = 15.4, 95% CI 4.9-48.0), cervix (OR = 4.3, 95% CI 2.7-6.9), and lymphoma/leukemia (OR = 3.9, 95% CI 1.5-10.4). Subsequent cancers were also in excess (relative risk (RR) = 1.4, 95% CI 1.1-1.7), particularly for the lung (RR = 2.3, 95% CI 1.3-3.7), bladder (RR = 2.3, 95% CI 1.0-4.6), breast (RR = 2.0, 95% CI 1.2-3.3), vulva/vagina (RR = 12.3, 95% CI 4.0-28.7), and small intestine (two cases) (RR = 10.8, 95% CI 1.2-39.0). Colorectal cancers were reduced (RR = 0.3, 95% CI 0.1-0.9). The data support a multifactorial etiology for anal cancer, in which an infectious agent and smoking may be involved. The association with lymphatic/hematopoietic cancers may indicate a possible role for immunodeficiency in anal cancer development. Multiple cancers occurred predominantly in patients diagnosed with anal cancer at a young age (< 60 years), which raises the possibility of a genetic predisposition for some cases. The authors recommend that, in future hypothesis generating and hypothesis testing multiple cancer studies of rare malignancies, the combined study of cancer events both prior to and following an index cancer should be considered.