The risk of colorectal cancer (CRC) is higher even in the third-degree relatives of persons with early-onset CRC, according to a new study published in Cancer Epidemiology. While the risk of developing the colorectal was observed to be 6-folds higher in the first-degree relatives, it was 1.5 times higher among the second- and third-degree relatives.^1.2

Researchers identified 1510 early-onset CRC cases in the Utah Population Data Base (UPDB) and assessed the risk in their first-, second-, and third-degree relatives. “The Utah Population Database (UPDB) at Huntsman Cancer Institute at the University of Utah is one of the world’s richest sources of in-depth information that supports research on genetics, epidemiology, demography, and public health. The UPDB is the only database of its kind in the United States and one of few such resources in the world.”

The relative risks for early-onset CRC among the first- and second-degree relatives were significantly higher than expected on the basis of UPDB disease rates for first-and second-degree relatives. The risk was found to be 6.0 times higher in the first-degree relatives, while the risk was 3.1 times higher among the second-degree relatives. Interestingly, the risk was observed to be 1.56 times higher even among the third-degree relatives.

Persons with a first-degree relative with early-onset CRC were at 2.64-fold higher risk for developing CRC at any age. The risk increased 1.96-folds with a second-degree relative and 1.3-folds with a third-degree relative.

The risk for CRC occurring either in the left or right colon was significantly higher for first-, second- or third-degree relatives although the location of the cancer in the relatives occasionally differed from that of the affected patient. The study authors also say that since more than 75% of the early-onset CRC cases were left-sided, it is unlikely that Lynch syndrome, which primarily occurs in the proximal colon influenced the results.

Family history is well-established non-modifiable risk factor for CRC. According to the American Cancer Society, “people with a history of colorectal cancer in a first-degree relative (parent, sibling, or child) are at increased risk. The risk is even higher if that relative was diagnosed with cancer when they were younger than 50 , or if more than one first-degree relative is affected”.

However, this study suggests that not only were the third-degree relatives at higher risk of developing early-onset CRC, they were also at risk of developing the cancer at any age. Hence, the study authors recommend making extended family history a part of the discussion when deciding on screening for CRC.

Current guidelines do not recommend screening for second- and possibly third-degree relatives of persons who have early-onset CRC unless Lynch syndrome or another genetic condition is identified. The latest 2021 American College of Gastroenterology (ACG) guidelines recommend screening for colorectal cancer in average-risk individuals aged 50 to 75 years, and suggest screening in average-risk persons aged 45 to 49 years. An average risk person is one with negative personal history of colorectal cancer or certain types of polyps or family history of colorectal cancer or personal history of IBD or confirmed or suspected hereditary colorectal cancer syndrome or prior history of radiotherapy.

The findings of this study therefore could have an impact on recommendations for screening for CRC. And forthcoming guidelines may consider early colonoscopy screening may be considered not only for first-degree relatives but also for second- and possibly third-degree relatives of persons who have early-onset CRC.

Reference

1. Early-onset HM, et al. Early-onset colorectal cancer risk extends to second- and third-degree relatives.  Cancer Epidemiol. 2021 Aug;73:101973.  doi: 10.1016/j.canep.2021.101973.
2. Increased risk for early-onset colorectal cancer extends to third-degree relatives - Medscape - Sep 30, 2021.