The risk of a second primary cancer following colorectal cancer (CRC) is significantly higher than expected cancer incidence rates for those without CRC, according to a study published online July 15 in CANCER.

The study revealed that the magnitude of this risk differed based on the location of the index CRC, with cases located in the transverse colon, splenic flexure and descending colon generating the greater risk increase, according to Amanda Phipps, PhD, MPH, of the University of Washington and Fred Hutchinson Cancer Research Center in Seattle, and colleagues.

“These subsites were also the locations at which there was the greatest absolute excess risk of a second primary CRC, indicating a generally greater susceptibility to second primary cancer in patients with index cancers in these colonic segments,” wrote the authors.

Previous work had suggested CRC survivors had a greater risk of developing another cancer, so Phipps and colleagues focused on evaluating whether this increased risk differed by subsite of the first CRC.

Included in the study were more than 170,000 individuals diagnosed with a first primary CRC between 1992 and 2009. This population was drawn from twelve Surveillance, Epidemiology, and End Results (SEER) cancer registries.

Those with a history of CRC had a 15 percent higher risk of developing a second cancer of any type compared to the general population, reported Phipps and colleagues. Those with cancers located in the traverse to descending regions of the colon had an approximately 30 percent increased overall risk and a two- to three-fold increased risk of a second CRC. Incidence of small intestinal cancer was elevated significantly no matter the subsite of the index CRC, while incidence of endometrial cancer was elevated in those with an index CRC in the proximal colon.

Phipps and colleagues speculated that the increased risks could stem from an underlying genetic predisposition in patients with familial cancer syndromes. “However, hereditary nonpolyposis colorectal cancer and other familial syndromes are rare and are unlikely to fully account for our findings. It is also possible that the increased risk of some cancers reflects misclassification of metastases as new primary cancers and/or reflects the contribution of shared risk factors.”

Another possibility is that the increased risk may be linked to environmental exposures and carcinogens, they added.

“Although the precise mechanisms underlying this pattern of increased risk are unclear, the current results suggest that strategies for cancer surveillance after an index CRC may need to be individualized according to subsite of the index CRC,” wrote the authors.