Genetics of Colorectal Cancer

Irfan M. Hisamuddin, MD; Vincent W. Yang, MD, PhD

Conclusion

Great progress has been made in the past 2 decades toward understanding the molecular genetics of CRC. Intense, ongoing research continues to shed light on new mechanisms of colorectal tumorigenesis. Despite this progress, there remains a relatively large population of individuals who have heritable CRC but an as yet unidentified genetic etiology. Advanced genetic testing hints at the vast potential of screening at-risk individuals, while, at the same time, the pitfalls of false-negative results remain to be addressed. An exciting future awaits us in the clinical application of new research and novel technologies that will ultimately lead to the universal goal -- better health for all.

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Funding information

This work was in part supported by grants from the National Institutes of Health (DK52230 and CA84197).

Cite this: Genetics of Colorectal Cancer - Medscape - Aug 13, 2004.

Clinical Criteria for the Diagnosis of HNPCC
The Amsterdam Criteria (1991)
Three or more relatives with colorectal cancer, plus all of the following: One affected patient should be a first-degree relative of the other 2; Colorectal cancer should involve at least 2 generations; and At least 1 case of colorectal cancer diagnosed before the age of 50 years.
Amsterdam II Criteria (1998)
Three or more relatives with HNPCC-associated cancer (colorectal cancer or cancer of the endometrium, small bowel, ureter, or renal pelvis) plus all of the following: One affected patient should be a first-degree relative of the other 2; Two or more successive generations should be affected; Cancer in 1 or more affected relatives should be diagnosed before the age of 50 years; Familial adenomatous polyposis should be excluded in any cases of colorectal cancer; and Tumors should be verified by pathologic examination.
The Bethesda Guidelines (1997)
Just 1 of these criteria needs to be met: Individuals with cancer in families that fulfill the Amsterdam criteria; Individuals with 2 HNPCC-related cancers, including synchronous and metachronous colorectal cancers or associated extracolonic cancers (which include endometrial, ovarian, gastric, hepatobiliary or small-bowel cancer, or transitional-cell carcinoma of the renal pelvis or ureter); Individuals with colorectal cancer and a first-degree relative with colorectal cancer and/or HNPCC-related extracolonic cancer and/or colorectal adenoma; one of the cancers must have been diagnosed before the age of 45 years and the adenoma diagnosed before the age of 40 years; Individuals with colorectal cancer or endometrial cancer that was diagnosed before the age of 45 years; Individuals with right-sided colorectal cancer with an undifferentiated pattern (solid/cribiform) on histopathology, which was diagnosed before the age of 45 years; Individuals with signet-ring-cell-type colorectal cancer that was diagnosed by the age of 45 years; or Individuals with adenomas that were diagnosed by the age of 40 years.

Clinical Criteria for the Diagnosis of HNPCC
The Amsterdam Criteria (1991)
Three or more relatives with colorectal cancer, plus all of the following: One affected patient should be a first-degree relative of the other 2; Colorectal cancer should involve at least 2 generations; and At least 1 case of colorectal cancer diagnosed before the age of 50 years.
Amsterdam II Criteria (1998)
Three or more relatives with HNPCC-associated cancer (colorectal cancer or cancer of the endometrium, small bowel, ureter, or renal pelvis) plus all of the following: One affected patient should be a first-degree relative of the other 2; Two or more successive generations should be affected; Cancer in 1 or more affected relatives should be diagnosed before the age of 50 years; Familial adenomatous polyposis should be excluded in any cases of colorectal cancer; and Tumors should be verified by pathologic examination.
The Bethesda Guidelines (1997)
Just 1 of these criteria needs to be met: Individuals with cancer in families that fulfill the Amsterdam criteria; Individuals with 2 HNPCC-related cancers, including synchronous and metachronous colorectal cancers or associated extracolonic cancers (which include endometrial, ovarian, gastric, hepatobiliary or small-bowel cancer, or transitional-cell carcinoma of the renal pelvis or ureter); Individuals with colorectal cancer and a first-degree relative with colorectal cancer and/or HNPCC-related extracolonic cancer and/or colorectal adenoma; one of the cancers must have been diagnosed before the age of 45 years and the adenoma diagnosed before the age of 40 years; Individuals with colorectal cancer or endometrial cancer that was diagnosed before the age of 45 years; Individuals with right-sided colorectal cancer with an undifferentiated pattern (solid/cribiform) on histopathology, which was diagnosed before the age of 45 years; Individuals with signet-ring-cell-type colorectal cancer that was diagnosed by the age of 45 years; or Individuals with adenomas that were diagnosed by the age of 40 years.

Clinical Criteria for the Diagnosis of HNPCC
The Amsterdam Criteria (1991)
Three or more relatives with colorectal cancer, plus all of the following: One affected patient should be a first-degree relative of the other 2; Colorectal cancer should involve at least 2 generations; and At least 1 case of colorectal cancer diagnosed before the age of 50 years.
Amsterdam II Criteria (1998)
Three or more relatives with HNPCC-associated cancer (colorectal cancer or cancer of the endometrium, small bowel, ureter, or renal pelvis) plus all of the following: One affected patient should be a first-degree relative of the other 2; Two or more successive generations should be affected; Cancer in 1 or more affected relatives should be diagnosed before the age of 50 years; Familial adenomatous polyposis should be excluded in any cases of colorectal cancer; and Tumors should be verified by pathologic examination.
The Bethesda Guidelines (1997)
Just 1 of these criteria needs to be met: Individuals with cancer in families that fulfill the Amsterdam criteria; Individuals with 2 HNPCC-related cancers, including synchronous and metachronous colorectal cancers or associated extracolonic cancers (which include endometrial, ovarian, gastric, hepatobiliary or small-bowel cancer, or transitional-cell carcinoma of the renal pelvis or ureter); Individuals with colorectal cancer and a first-degree relative with colorectal cancer and/or HNPCC-related extracolonic cancer and/or colorectal adenoma; one of the cancers must have been diagnosed before the age of 45 years and the adenoma diagnosed before the age of 40 years; Individuals with colorectal cancer or endometrial cancer that was diagnosed before the age of 45 years; Individuals with right-sided colorectal cancer with an undifferentiated pattern (solid/cribiform) on histopathology, which was diagnosed before the age of 45 years; Individuals with signet-ring-cell-type colorectal cancer that was diagnosed by the age of 45 years; or Individuals with adenomas that were diagnosed by the age of 40 years.

Clinical Criteria for the Diagnosis of HNPCC
The Amsterdam Criteria (1991)
Three or more relatives with colorectal cancer, plus all of the following: One affected patient should be a first-degree relative of the other 2; Colorectal cancer should involve at least 2 generations; and At least 1 case of colorectal cancer diagnosed before the age of 50 years.
Amsterdam II Criteria (1998)
Three or more relatives with HNPCC-associated cancer (colorectal cancer or cancer of the endometrium, small bowel, ureter, or renal pelvis) plus all of the following: One affected patient should be a first-degree relative of the other 2; Two or more successive generations should be affected; Cancer in 1 or more affected relatives should be diagnosed before the age of 50 years; Familial adenomatous polyposis should be excluded in any cases of colorectal cancer; and Tumors should be verified by pathologic examination.
The Bethesda Guidelines (1997)
Just 1 of these criteria needs to be met: Individuals with cancer in families that fulfill the Amsterdam criteria; Individuals with 2 HNPCC-related cancers, including synchronous and metachronous colorectal cancers or associated extracolonic cancers (which include endometrial, ovarian, gastric, hepatobiliary or small-bowel cancer, or transitional-cell carcinoma of the renal pelvis or ureter); Individuals with colorectal cancer and a first-degree relative with colorectal cancer and/or HNPCC-related extracolonic cancer and/or colorectal adenoma; one of the cancers must have been diagnosed before the age of 45 years and the adenoma diagnosed before the age of 40 years; Individuals with colorectal cancer or endometrial cancer that was diagnosed before the age of 45 years; Individuals with right-sided colorectal cancer with an undifferentiated pattern (solid/cribiform) on histopathology, which was diagnosed before the age of 45 years; Individuals with signet-ring-cell-type colorectal cancer that was diagnosed by the age of 45 years; or Individuals with adenomas that were diagnosed by the age of 40 years.

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Genetics of Colorectal Cancer

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