From the AGA Journals

Study backed familial component of advanced adenoma risk

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Study supports earlier CRC screening of first-degree relatives of CRC patients

Current guidelines recommend early screening and shorter surveillance intervals in individuals with a first-degree relative (FDR) with colorectal cancer (CRC) (Gastroenterology. 2008;134:1570-950). Existing literature is limited by either lack of an appropriate comparison group or inability to assess adenoma risk in subjects who have an FDR with adenomas.

Dr. Harini S. Naidu

To date, this is the first prospective study to demonstrate increased prevalence of advanced adenomas in siblings of probands with advanced adenomas detected during colonoscopy. The authors should be congratulated on completing an organized, well-powered study using colonoscopy and histopathology and were careful to limit familial clustering by randomly selecting only one sibling from each family. Although this study has important findings, there are a few points worthy of consideration.

First, it would be helpful to understand whether the siblings shared both parents, one parent, or were adopted, as this would affect the genetic implications of the findings.

Second, the analysis did not stratify probands and siblings based on whether the colonoscopy included in the study was the first or second screening, or surveillance colonoscopy. The risk of advanced adenomas is expected to be different in someone with numerous normal colonoscopies, compared with someone undergoing their initial screening colonoscopy, and this point deserves clarification.

Dr. Audrey H. Calderwood

Third, it would be helpful to know how many siblings in each group were excluded due to previous adenomas, which bias results towards the null. For example, exclusion of high-risk individuals with previous adenomas in the control group may make the prevalence of adenoma detection appear lower if only lower-risk individuals are included.

Lastly, this study was performed in a uniform Asian patient population, and may not be generalizable to other populations. Validation in a more ethnically heterogeneous setting is warranted. Overall, this is a solid, clinically relevant study that can help inform the impact of family history of advanced adenomas on CRC screening recommendations.

In addition, the study’s findings corroborate the American College of Gastroenterology’s recommendations for earlier CRC screening at shorter surveillance intervals in patients who have FDRs with advanced adenomas detected at age less than 60, or two FDRs diagnosed with advanced adenomas at any age (Am J Gastroenterol. 2009;104:739–50).

Dr. Harini S. Naidu and Dr. Audrey H. Calderwood are in the section of gastroenterology, Boston University. The authors have no conflicts of interest to declare.


 

FROM GASTROENTEROLOGY

References

Siblings of patients with advanced adenoma had sixfold higher odds of having the tumors themselves, as compared with controls, said the authors of a blinded cross-sectional study reported in the March issue of Gastroenterology.

The results reinforce the need for early screening of individuals whose siblings have advanced adenoma, said Dr. Siew Ng at the Chinese University of Hong Kong and her associates. The risk of advanced adenoma was even higher when affected probands were younger than average or had multiple adenomas, the researchers added.

Most studies that have purported to study the familial risk of adenoma actually studied the risk of adenoma in persons whose first-degree relatives have colorectal cancer, according to Dr. Ng and her associates. Their study included 200 asymptomatic (“exposed”) siblings of individuals with advanced adenomas as diagnosed on colonoscopy, and 400 controls whose siblings had no family history of colorectal cancer or colonoscopic evidence of neoplasia. The researchers defined advanced adenomas as those measuring at least 10 mm or that had high-grade dysplasia or villous or tubulovillous characteristics. “We focused on advanced lesions, as they have the greatest malignant potential, and removing these lesions can reduce colorectal cancer incidence and mortality,” they said (Gastroenterology. 2015 Nov 14. doi: 10.1053/j.gastro.2015.11.003).

Exposed siblings were consistently more likely to have adenomas themselves, compared with the control group, said the investigators. For example, the prevalence of any advanced adenoma was 11.5% among exposed siblings compared with only 2.5% among controls (matched odds ratio, 6.05; 95% confidence interval, 2.7-13.4; P less than .001). Similarly, the prevalence of adenomas measuring at least 10 mm was 10.5% among exposed individuals and 1.8% among controls (mOR, 8.6; 95% CI, 3.4-21.4; P less than .001). The prevalence of villous adenomas was 5.5% among exposed individuals and 1.3% among controls (mOR, 6.3; 95% CI, 2.0-19.5; P = .001) and the prevalence of all colorectal adenomas was 39% among exposed individuals and 19% among controls (mOR, 3.3; 95% CI, 2.2-5.0; P less than .001). Finally, two cases of colorectal cancer were detected among the exposed siblings, while no such cases were detected among the controls.

The exposed siblings and controls resembled each other in terms of aspirin use, smoking, body mass index, and metabolic diseases, the researchers said. However, the probands with adenoma were identified from a consecutive group of patients, while control siblings were enrolled through a screening program, they said. Therefore, the groups might have differed in terms of unmeasured environmental risk factors for cancer, such as physical activity and dietary habits. They also noted the difficulties in obtaining accurate family histories of colonic neoplasia, especially distinguishing adenoma from advanced adenoma. Finally, Hong Kong is ethnically homogenous, and the data might not be generalizable to other populations, although Asia and Western countries do tend to have comparable rates of advanced adenoma in average-risk individuals and in families with histories of colorectal neoplasias.

The Research Grants Council of the Hong Kong Special Administrative Region funded the study. The investigators had no disclosures.

Source: American Gastroenterological Association

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