Clinical Management of Hereditary Colorectal Cancer Syndromes
Clinical Management of Hereditary Colorectal Cancer Syndromes
Purpose of Review: Colorectal cancer is the second leading cause of cancer-related death in the United States. Although most colorectal cancers are sporadic, approximately 25% have a familial predisposition, and 5 to 7% are hereditary and occur in genetically distinct high-risk families. This review focuses on four hereditary colon cancer syndromes: familial adenomatosus polyposis, hereditary nonpolyposis colorectal cancer, juvenile polyposis syndrome, and Peutz-Jeghers syndrome.
Recent Findings: The management of the inherited colorectal cancer syndromes has progressed substantially over the past years because of advancement of genetic understanding and testing options, which have led to the possibility of preclinical diagnosis and early surveillance and treatment. Genetic testing is based on identification of specific abnormalities and should be combined with counseling of affected families.
Summary: Recent advances have contributed to the understanding of the molecular basis of various types of colorectal cancer, and among these, the inherited colorectal cancer syndromes have attracted much attention. Expanding recognition of clinical characteristics, targeted surveillance strategies and new methods of treatment have led to improved clinical management of these syndromes.
Colorectal cancer represents a major cause of morbidity and mortality in the United States and in countries with similar lifestyles. With an estimated 148,300 new cases and 56,600 deaths in 2002, colorectal cancer is the third most common cancer and the second leading cause of cancer-related death among men and women in the United States. Without preventive interventions, approximately 6% of Americans will develop colorectal cancer at some point during their lives. Cancer is a genetic disorder, meaning that genetic mutations confer growth advantage for tumor cells. The genetic component may be acquired (sporadic) or inherited.
Twenty percent of colon cancers are considered familial colon cancer, in which colon cancer develops more frequently in a specific family relative to the general population but not in a pattern consistent with an inherited syndrome. It has become increasingly clear that genetic predisposition plays a role in a significant number of patients with colorectal cancer. The risk of colorectal cancer increases twofold relative to the general population when one or more first-degree relatives have a history of colorectal cancer. The risk increases significantly if the first-degree relative had a colorectal cancer or an adenomatous polyp diagnosed before the age of 60 years. Furthermore, the risk is higher if more than one first-degree relative is affected at any age. Colorectal cancer even in second-degree relatives (grandparents, aunts, uncles) or third-degree relatives (great-grandparents, cousins) was found to increase risk for this cancer by approximately 50% compared with the general population.
Approximately 5 to 10% of colorectal cancers have an inherited predisposition in an autosomal-dominant manner. The two major contributors are familial adenomatous polyposis (1%) and hereditary nonpolyposis colorectal cancer (3-6%). Other inherited syndromes such as juvenile polyposis and Peutz-Jeghers syndrome are also discussed.
Abstract and Introduction
Abstract
Purpose of Review: Colorectal cancer is the second leading cause of cancer-related death in the United States. Although most colorectal cancers are sporadic, approximately 25% have a familial predisposition, and 5 to 7% are hereditary and occur in genetically distinct high-risk families. This review focuses on four hereditary colon cancer syndromes: familial adenomatosus polyposis, hereditary nonpolyposis colorectal cancer, juvenile polyposis syndrome, and Peutz-Jeghers syndrome.
Recent Findings: The management of the inherited colorectal cancer syndromes has progressed substantially over the past years because of advancement of genetic understanding and testing options, which have led to the possibility of preclinical diagnosis and early surveillance and treatment. Genetic testing is based on identification of specific abnormalities and should be combined with counseling of affected families.
Summary: Recent advances have contributed to the understanding of the molecular basis of various types of colorectal cancer, and among these, the inherited colorectal cancer syndromes have attracted much attention. Expanding recognition of clinical characteristics, targeted surveillance strategies and new methods of treatment have led to improved clinical management of these syndromes.
Introduction
Colorectal cancer represents a major cause of morbidity and mortality in the United States and in countries with similar lifestyles. With an estimated 148,300 new cases and 56,600 deaths in 2002, colorectal cancer is the third most common cancer and the second leading cause of cancer-related death among men and women in the United States. Without preventive interventions, approximately 6% of Americans will develop colorectal cancer at some point during their lives. Cancer is a genetic disorder, meaning that genetic mutations confer growth advantage for tumor cells. The genetic component may be acquired (sporadic) or inherited.
Twenty percent of colon cancers are considered familial colon cancer, in which colon cancer develops more frequently in a specific family relative to the general population but not in a pattern consistent with an inherited syndrome. It has become increasingly clear that genetic predisposition plays a role in a significant number of patients with colorectal cancer. The risk of colorectal cancer increases twofold relative to the general population when one or more first-degree relatives have a history of colorectal cancer. The risk increases significantly if the first-degree relative had a colorectal cancer or an adenomatous polyp diagnosed before the age of 60 years. Furthermore, the risk is higher if more than one first-degree relative is affected at any age. Colorectal cancer even in second-degree relatives (grandparents, aunts, uncles) or third-degree relatives (great-grandparents, cousins) was found to increase risk for this cancer by approximately 50% compared with the general population.
Approximately 5 to 10% of colorectal cancers have an inherited predisposition in an autosomal-dominant manner. The two major contributors are familial adenomatous polyposis (1%) and hereditary nonpolyposis colorectal cancer (3-6%). Other inherited syndromes such as juvenile polyposis and Peutz-Jeghers syndrome are also discussed.