We appreciate the interest in our article and thank Berstad and colleagues for their kind comments about its importance. As noted in our Discussion, we concur with their speculation that the notable absence of several important risk factors for advanced colorectal neoplasia (ACN) may be largely responsible for the Your Disease Risk (YDR) index's lack of accuracy for discriminating low from intermediate/high-risk individuals. Besides cigarette smoking, there is a compelling body of evidence to suggest that the use of nonaspirin nonsteroidal anti-inflammatory agents (NSAID) may also be an important determinant of risk (1). Similarly, both race (2) and type II diabetes mellitus (3) have also been identified as potential risk factors, but like smoking and NSAID use, neither is included in the index.

We also acknowledge the possibility that the index's lack of accuracy may also be due to the inclusion of putative risk factors for which the assigned relative risk or latency of exposure might differ for cancers compared with advanced adenomas, particularly in light of our understanding of the adenoma-carcinoma sequence (4).

Notwithstanding these considerations, our findings in no way refute the YDR index's validity for providing 10-year risk estimates for colorectal cancer. Nevertheless, we hope our findings serve as an impetus for reevaluating the performance of the index for its intended use and/or revising its content in accordance with new insight into the epidemiology of ACN.

See the original Letter to the Editor, p. 1405

No potential conflicts of interest were disclosed.

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