‘Frequent polyp diagnoses’ in near relatives linked to higher colorectal cancer risk
Key takeaways:
- The frequency of polyp diagnoses in close relatives was strongly associated with colorectal cancer risk.
- Polyp history in second-degree relatives was only influential with multiple polyp diagnoses.
People with first-degree relatives who were repeatedly diagnosed with colorectal polyps appeared at increased risk for colorectal cancer, especially early-onset CRC, according to a study published in Gastroenterology.
“Our study highlights a subset of individuals at very high risk for early-onset colorectal cancer, which current screening guidelines do not adequately address,” Mahdi Fallah, MD, PhD, leader of the Risk Adapted Cancer Prevention Group of the German Cancer Research Center in Heidelberg, Germany, and visiting professor in clinical epidemiology at Lund University in Sweden, told Healio.
“There’s a pressing need for personalized screening guidelines that consider the frequency of polyp diagnoses in family members to potentially reduce CRC incidence and mortality,” Fallah added.
Family history vs. polyp frequency
Prior studies have shown an association between increased risk for CRC and family history of colorectal polyps, but they did not reflect how lower or higher frequencies of such diagnosis impact this relationship.
This inspired the researchers to conduct a retrospective, population-based study to examine the relationship between family history of benign colorectal polyps and risk for CRC, including factors such as frequency of polyp diagnosis in relatives, number of first-degree and second-degree relatives with polyps, and youngest age at polyp diagnosis.
The study included 11.6 million individuals (51% men) registered with nationwide Swedish family cancer datasets who had at least one known first-degree relative. The researchers pulled family lineage, family history of polyps and 1964 to 2018 clinical visit data from these datasets. They used that data to calculate standardized incidence ratios (SIRs) of overall and early-onset CRC for participants with a family history of polyps by frequency of polyp diagnosis in relatives.
Over a median follow-up of 31 years, 162,927 individuals from the cohort were diagnosed with CRC.
In total, 196,910 relatives were diagnosed with colorectal polyps. Of that group, a majority (n = 162,769) had only one-time polyp diagnosis whereas the remainder (n = 34,141) had frequent (two or more) polyp diagnoses.
Polyp frequency, not just presence, defined risk
The researchers found that risk for CRC — particularly early-onset CRC — increased among individuals with a family history of polyps as the number of first-degree relatives with polyps and their frequency of polyp diagnosisv increased.
Specifically, compared with those without any family history of polyps, participants with one first-degree relative with one polyp diagnosis had a 1.35-fold (95% CI, 1.32-1.38) higher risk for CRC overall and a 1.45-fold (95% CI, 1.34-1.55) higher risk for early-onset CRC.
This risk increased if participants had one first-degree relative with frequent polyp diagnoses (overall: SIR = 1.82; 95% CI, 1.76-1.88; early-onset: SIR = 2.27; 95% CI, 1.99-2.58) or two or more first-degree relatives with one-time polyp diagnosis (overall: SIR = 1.89; 95% CI, 1.73-2.06; early-onset: SIR = 2.16; 95% CI, 1.55-2.93).
However, risk for overall CRC as well as early-onset CRC was greatest among participants with two or more first-degree relatives with frequent polyp diagnoses (overall: SIR = 2.44; 95% CI, 2.2-2.69; early-onset: SIR = 3.92; 95% CI, 2.83-5.3).
Further, the researchers found that younger age of a first-degree relative when diagnosed with polyps was linked to increased risk for CRC, but no such trend was observed among second-degree relatives. For example, when a first-degree relative was diagnosed only once with polyps before age 50 years or between age 50 to 59 years, overall risk for CRC was about 1.5-fold higher compared with 1.28-fold higher when diagnosed at age 60 years or older.
Finally, the researchers concluded that second-degree relatives with a history of polyps only impacted risk for CRC when those relatives had frequent polyp diagnoses.
There were several limitations to this study, Fallah told Healio, including a “lack of detailed information on polyp characteristics (size, number and histology)” and the researchers’ “inability to adjust for all potential confounders like smoking and physical activity.”
However, he noted that their usage of one of the largest family cancer datasets, which includes 11.7 million individuals and significant long-term follow-up, provides “robust evidence with high statistical power.”
“The findings suggest that clinicians should consider not only the presence of colorectal polyps in family members but also how often these polyps have been diagnosed when assessing the risk of colorectal cancer in individuals,” Fallah added. “This could lead to more tailored screening strategies, potentially starting screening earlier or more frequently for those with a family history of frequent polyp diagnoses.”
Future studies could focus on the genetic and environmental factors that contribute to the frequency of polyp diagnoses or proactively track polyp frequency over time with modern screening technologies, he said.
For more information:
Mahdi Fallah, MD, PhD, can be reached at m.fallah@dkfz.de or on X (Twitter) @DrFallah1.
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