Hereditary nonpolyposis colorectal cancer (HNPCC) is a dominantly inherited syndrome characterized by significantly increased risks for colon cancer as well as for cancers of the endometrium, stomach, small intestine, kidney, ureter and ovary, according to background information in the article. Many experts currently use the term HNPCC synonymously with a hereditary DNA mismatch repair (MMR, a mechanism that corrects errors made during DNA replication) gene deficiency, and studies of cancer risks in the syndrome have generally focused on families with MMR deficiency.

Approximately 60 percent of families that meet criteria for a certain type of HNPCC, Amsterdam-I (AC-I) have an abnormality in a DNA MMR gene. Cancer incidence in AC-I families with MMR gene mutations is reported to be high, but cancer incidence for individuals in AC-I families with no evidence of an MMR defect has been unknown, as are appropriate screening guidelines.

Noralane M. Lindor, M.D., of the Mayo Clinic, Rochester, Minn., and colleagues identified 161 families in North America and Germany meeting AC-I criteria and analyzed the family history for cancer incidences. The families were stratified into those with (group A) or without (group B) MMR deficiency by tumor testing. A total of 3,422 relatives were included in the analyses.

The researchers found that group A families had increased incidences for cancers of the colorectum, endometrium, stomach, small intestine, and ureter, but no increases in incidence of cancer of the breast, lung, prostate, or other sites. Group B families showed only a modest increase in the incidence of colorectal cancer, and no increase in the risk of other malignancies.

"The literature regarding cancer risks in AC-I families without MMR deficiency has been very limited but has hinted that could be differences from the AC-I families with MMR deficiency. Thus, in counseling such families, clinicians can now provide them with more accurate and lower-risk information, using these new data in combination with the specific family history," the authors write.

"The use of HNPCC as a label needs to be refined or made obsolete. The term HNPCC encompasses considerable heterogeneity and has come to mean different entities to difference people," the researchers write. "These families [AC-I families without MMR deficiency] should not be described or counseled as having HNPCC-Lynch syndrome [families with MMR deficiency]. To facilitate distinguishing these entities, the designation of 'familial colorectal cancer type X' is suggested to describe this type of familial aggregation of colorectal cancer."

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