Jiao Yang, Shuting Li, Meng Lv, Yinying Wu, Zheling Chen, Yanwei Shen, Biyuan Wang, Ling Chen, Min Yi, Jin Yang

The site-distribution pattern and relative risk of subsequent primary malignancies (SPMs) in colorectal cancer (CRC) patients remains to be determined. A population-based cohort of 288,390 CRC patients diagnosed between 1973 and 2012 from the Surveillance, Epidemiology, and End Results database was retrospectively reviewed. Standardized incidence ratios were calculated to estimate the relative risk for SPMs. The overall risk of SPMs increased in CRC patients (standardized incidence ratio 1.02) in the first 5 years after CRC diagnosis compared with that in the general population, and was negatively related to age at diagnosis. Risk increased significantly for cancers of the small intestine, ureter, colorectum, renal pelvis, endocrine system, and stomach, and decreased significantly for cancers of the gallbladder, liver, myeloma, and brain, as well as lymphoma. Patients with different prior CRC subsites showed specific sites at high risk of SPM. Prior right-sided colon cancer was associated with cancers of the small intestine, ureter, renal pelvis, thyroid, stomach, pancreas, and breast and prior left-sided colon cancer associated with secondary CRC, whereas rectal cancer was associated with cancers of the vagina, urinary bladder, and lung. Risk of SPMs increases in CRC survivors, especially in the first 5 years after prior diagnosis. Intensive surveillance should be advocated among young patients, with specific attention to the small intestine, colorectum, renal pelvis, and ureter. The common sites at high risk of SPM originate from the embryonic endoderm. Genetic susceptibility may act as the main mechanism underlying the risk of multiple cancers.