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Hereditary colorectal cancer risk lowered in those without certain gene defect

Families with a certain type of hereditary colorectal cancer have a reduced cancer risk if they do not have a gene defect found in many with this type of cancer risk, according to a study in the April 27 issue of JAMA.

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.

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Contact: Cathryn Stroebel
507-266-0810
JAMA and Archives Journals
26-Apr-2005


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