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Intestinal polyps in close relatives can increase risk of CRC

Tue, 05/04/2021 - 14:55
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In the largest registry study to date, researchers at Karolinska Institutet and Harvard University in the USA, have reported a possible connection between colorectal polyps in close relatives and the risk of developing colorectal cancer. The study, ‘Risk of colorectal cancer in first degree relatives of patients with colorectal polyps: nationwide case-control study in Sweden’, published in the British Medical Journal, is of potential consequence for different countries' screening procedures.

"The risk was double in people with at least two first-degree relatives with polyps or a first-degree relative who had a colorectal polyp diagnosed before the age of 60," explained the study's first author, Dr Mingyang Song from Harvard University.

The study included 68,060 patients with colorectal cancer and 333,753 healthy controls matched for parameters such as age and sex. Data on colorectal cancer and polyps were sourced from the ESPRESSO (Epidemiology Strengthened by Histopathology Reports in Sweden) cohort. All other patient data were drawn from Swedish healthcare registries.

The results show that heredity for colorectal polyps had a 40 per cent increased risk of colorectal cancer. After adjusting for family history of CRC and other covariates, having a first degree relative with a colorectal polyp (8.4% (5742/68 060) in cases and 5.7% (18 860/333 753) in controls) was associated with a higher risk of CRC (odds ratio 1.40, 95% confidence interval 1.35 to 1.45). The odds ratios ranged from 1.23 for those with hyperplastic polyps to 1.44 for those with tubulovillous adenomas.

The researchers then examined the age specific absolute risk of colon and rectal cancers according to family history of polyps based on the 2018 national CRC incidence in Sweden. The absolute risk of colon cancer in individuals aged 60-64 years with and without a family history of colorectal polyp was, respectively, 94.3 and 67.9 per 100 000 for men and 89.1 and 64.1 per 100 000 for women.

The researchers found what appear to be several hereditary risk relationships. The association between family history of polyps and CRC risk was strengthened by the increasing number of first degree relatives with polyps (≥2 first degree relatives: 1.70, 1.52 to 1.90, p<0.001 for trend) and decreasing age at polyp diagnosis (<50 years: 1.77, 1.57 to 1.99, p<0.001 for trend).

They found a particularly strong association for early onset CRC diagnosed before age 50 years (≥2 first degree relatives: 3.34, 2.05 to 5.43, p=0.002 for heterogeneity by age of CRC diagnosis). In the joint analysis, the odds ratio of CRC for individuals with two or more first degree relatives with polyps but no CRC was 1.79 (1.52 to 2.10), with one first degree relative with CRC but no polyps was 1.70 (1.65 to 1.76), and with two or more first degree relatives with both polyps and CRC was 5.00 (3.77 to 6.63) (p<0.001 for interaction).

A weakness of the study is the lack of information on other risk factors of colorectal cancer, such as lifestyle factors as well as the size and spread of the polyps. More research is now needed to corroborate the results.

"If additional studies reveal a link between a family history of polyps and the risk of colorectal cancer, it is something to take into account in the screening recommendations, especially for younger adults," added Dr Jonas F Ludvigsson, paediatrician at Örebro University Hospital and professor at the Department of Medical Epidemiology and Biostatistics, Karolinska Institutet. "I really hope that this study can help doctors in Sweden and elsewhere identify patients at a higher risk of colorectal cancer."

The study was financed by the National Institutes of Health and the American Cancer Society. Ludvigsson heads an unrelated study commissioned by the Swedish IBD Quality Registry (SWIBREG) financed by Janssen.

To access this paper, please click here