Asymptomatic siblings of Chinese colorectal cancer patients are at threefold higher risk for advanced colorectal neoplasms and at twofold higher risk for any colorectal adenoma, compared with siblings of healthy Chinese adults, Dr. Siew C. Ng and her colleagues reported in the March issue of Gastroenterology (doi:10.1053/j.gastro.2012.11.011).
Given these findings from a large prospective cross-sectional study, colorectal screening, with the removal of any premalignant lesions that are found, is warranted in this high-risk group, said Dr. Ng of the Prince of Wales Hospital and the Chinese University of Hong Kong and her associates.
Current guidelines recommend earlier and more frequent screening of close relatives of patients who have colorectal cancer, but what to expect on these screenings is unclear because "data from well-conducted prospective studies are lacking," they said.
Dr. Ng and her colleagues compared the prevalence of advanced neoplasms in such siblings against the prevalence in siblings of patients who underwent colorectal screening but had normal results. "The use of such a control group avoids a biased estimate of the association with family history, and removes the acquired or environmental component to this association," the investigators wrote.
All the screenings used a conventional white-light colonocope without high definition and were performed with patients under conscious sedation with intravenous midazolam and pethidine.
During a period of 10 years, 374 siblings (mean age, 53 years) of CRC patients aged 40-70 years participated in the study, as did 374 age- and sex-matched control subjects. The quality of bowel preparation was similar between the two groups.
All three study endoscopists were experienced, and they had comparable rates of adenoma detection.
The primary outcome was the prevalence of advanced neoplasms, defined as cancers or adenomas at least 10 mm in diameter that had high-grade dysplasia or villous/tubovillous histologic traits. This prevalence was approximately three times higher in the siblings of CRC patients (7.5%) as in the siblings of healthy controls (2.9%), with an odds ratio of 3.07.
Adenocarcinomas were detected in six siblings of CRC patients, but in none of the control subjects. These included two stage I cancers, two stage II cancers, and two stage III cancers.
Similarly, the prevalence of large adenomas was approximately three times as high in siblings of CRC patients (5.9%) as in controls (2.1%).
Siblings of CRC patients also had a higher prevalence of smaller adenomas (31%) than did control subjects (18.2%).
When the data were analyzed by lesion location, the siblings of CRC patients had a higher prevalence of every type: distal adenomas (13.1% vs. 8.3%), proximal adenomas (12.0% vs. 6.2%), and synchronous adenomas (5.9% vs. 2.7%).
The prevalence of hyperplastic polyps was comparable between the two groups (27.3% and 21.4%).
When the data were analyzed by subject age, siblings of CRC patients had a higher prevalence of all colorectal adenomas whether they were younger than 50 years (21.0% vs. 9.8%), 50-60 years old (34.4% vs. 23.9%), or older than 60 years (41.0% vs. 20.5%).
The study findings remained robust in two further sensitivity analyses.
Among the siblings of CRC patients, the risk of detecting an advanced adenoma was higher if the affected sibling’s cancer was located in the distal colon than if it was located in the proximal colon. This risk also was higher if the affected sibling was a woman than a man; however, this finding must be interpreted with caution because the number of subjects in these subgroups was small.
These study results can be used to "provide a background against which screening strategies can be formulated." More important, the strong, significantly increased risk of advanced neoplasms means that siblings of CRC patients should be screened carefully, Dr. Ng and her associates said.