Colorectal carcinoma (CRC) has been described as a subsequent malignant neoplasm (SMN), although little is known about associated risk factors. We aimed to quantify the long-term risk of secondary CRC and identify treatment-related risk factors.

In this nested case-control study, 19 cases of adenocarcinoma of the colon or rectum were identified from 13,048 oncology patients treated for childhood cancer at St Jude Children's Research Hospital. Group 1 controls (n = 148) were matched for age at primary malignancy and follow-up interval. Group 2 controls (n = 72) were matched on primary diagnosis in addition to group 1 criteria. Exact conditional logistic regression was performed to calculate odds ratios (ORs) for chemotherapy and radiation exposure.

Forty-year cumulative incidence of secondary CRC was 1.4%. Standardized incidence ratio was 10.9 (95% CI, 6.6 to 17.0) compared with that in the general US population. Secondary CRC was more likely in an irradiated segment of the colon (group 1 OR, 7.7; P = .001; group 2 OR, 15.4; P = .002). Risk increased by 70% with each 10-Gy increase in radiation dose. Increasing radiation volume increased risk (group 1 OR, 1.5; P < .001; group 2 OR, 1.8; P < .001). Alkylating agent exposure was associated with an 8.8-fold increased risk of secondary CRC (P = .03).

In matched analyses, radiation and alkylator exposure are associated with secondary CRC. This risk is proportional to dose and volume of radiation. Surveillance should be initiated at a young age among survivors receiving high-risk exposures.