© 2005 Oxford University Press
CORRESPONDENCE |
RESPONSE: Re: Revised Bethesda Guidelines for Hereditary Nonpolyposis Colorectal Cancer (Lynch Syndrome) and Microsatellite Instability
Correspondence to: Asad Umar, DVM, PhD, National Cancer Institute, National Institutes of Health, 6130 Executive Blvd., EPN 2141, Bethesda, MD 20892 (e-mail: asad.umar{at}nih.gov).
Investigators have just started to evaluate the Revised Bethesda Guidelines by examining their sensitivity, specificity, and positive predictive value in various populations. How these new revised guidelines will compare with the Amsterdam criteria, the revised Amsterdam criteria, the Japanese guidelines (1), or even the original Bethesda Guidelines over time is a valid scientific question. This question must be answered in the light of scientific data rather than the belief that the Revised Bethesda Guidelines seem to be less effective if the commentary accompanying them was "poorly worded or confusing."
The Revised Bethesda Guidelines published in the Journal (1) represent a close consensus of the overall recommendations made at the workshop of hereditary nonpolyposis colorectal cancer (HNPCC; Lynch syndrome) experts, including Dr. Lynch (2) and other pioneers in the field, whereas the Nature Reviews Cancer publication is a perspective on the guidelines across the world and more of a discussion (3). Despite some editorial variations (adenoma diagnosis before age 40 years was not finalized at the point of the Nature Reviews Cancer publication), the Revised Bethesda Guidelines presented in the two publications are identical [Table 1 and (1)]. Inclusion or exclusion of adenomas was a topic of discussion at the workshop and led to the decision to revise the original Bethesda Guidelines, as discussed in the JNCI commentary (1). In addition, we have also contributed to the publication of a dedicated issue of the journal Disease Markers (4) with a detailed commentary and point of view from many of the investigators present at the workshop of HNPCC (Lynch syndrome) experts who suggested changes to the guidelines.
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The suggestion of Macrae and Harris that everyone with bowel cancer is likely to have at least two relatives with colorectal cancer if the pedigree is pursued extensively enough is not justified by the available data. Approximately 15% of individuals with colorectal cancer will have a first-degree relative with the disease; very little data are currently available regarding the prevalence of colorectal cancer in second-degree relatives among colorectal cancer patients. Adding second-degree relatives to the guidelines may decrease specificity, but it will also increase sensitivity by identifying cases that would have been missed using first-degree family history alone. Limiting Guideline 5 to the same side of the family may increase specificity and reflect the Mendelian nature of HNPCC inheritance. We do still include endometrial cancer in the revised guidelines as an HNPCC-associated tumor in footnote 1 (Table 1). A detailed discussion of HNPCC-related pathology can be found in the special issue of Disease Markers (4).
The meeting's participants recognized that a fair amount of data exist that are too controversial to develop a consensus for many of these guidelines. The Revised Bethesda Guidelines should be considered a work in progress and by no means suggest that the original Bethesda Guidelines are obsolete; one should see them as milestones toward achieving general agreement for use by practicing physicians.
REFERENCES
(1) Umar A, Boland R, Terdiman JP, Syngal S, de la Chapelle A, Ruschoff J, et al. Revised Bethesda Guidelines for Hereditary Nonpolyposis Colorectal Cancer (Lynch Syndrome) and Microsatellite Instability. J Natl Cancer Inst 2004;96:261–8.
(2) Lynch HT, Lynch JF. Lynch syndrome: history and current status. Dis Markers 2004;20:181–98.[Medline]
(3) Umar A, Risinger JI, Hawk ET, Barrett JC. Testing guidelines for hereditary non-polyposis colorectal cancer. Nat Rev Cancer 2004;4:153–8.[Web of Science][Medline]
(4) Umar A. Disease markers: Lynch syndrome (HNPCC) and microsatellite instability. Amsterdam (The Netherlands): IOS Press; 2004.
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J Natl Cancer Inst 2005 97: 936-937.
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