- Hereditary nonpolyposis colorectal cancer (HNPCC) or Lynch syndrome: mismatch repair (MMR) genes.
- Peutz-Jeghers syndrome: STK11/LKB1 gene.
- Juvenile polyposis syndrome: SMAD4/DPC4 and BMPR1A genes.
- Cowden syndrome: PTEN gene.
- Ruvalcaba-Myhre-Smith syndrome: PTEN gene.
- Hereditary mixed polyposis syndrome.
HNPCC, the result of defects in MMR genes (involving hMSH2, hMLH1, hPMS1, hPMS2, or hMSH6) represents the most common form of hereditary colorectal cancer, accounting for approximately 3% to 5% of all colorectal malignancies. The majority of genetically defined cases involve hMSH2 on chromosome 2p, and hMLH1 on chromosome 3p. In affected families, 15% to 60% of family members are found to have mutations in hMSH2 or hMLH1; the mutation prevalence depends on features of the family history. Ashkenazi Jews also have an increased risk for colorectal cancer related to a mutation in the APC gene (I1307K), which occurs in 6% to 7% of the Ashkenazi Jewish population.
Other risk factors
More common conditions with an increased risk include:
- Personal history of colorectal cancer or colorectal adenomas.
- First-degree family history of colorectal cancer or colorectal adenomas.
- Personal history of ovarian, endometrial, or breast cancer.[13,14]
These high-risk groups account for only 23% of all colorectal cancers. Limiting screening or early cancer detection to only these high-risk groups would miss the majority of colorectal cancers. (Refer to the PDQ summaries on Colorectal Cancer Screening and Colorectal Cancer Prevention for more information.)
Clinical Presentation and Symptoms
Similar to colon cancer, symptoms of rectal cancer may include the following:
- Gastrointestinal bleeding.
- Change in bowel habits.
- Abdominal pain.
- Intestinal obstruction.
- Weight loss.
- Change in appetite.
Excepting obstructive symptoms, the symptoms of rectal cancer neither necessarily correlate with the stage of disease nor signify a particular diagnosis. Physical examination may reveal a palpable mass and bright blood in the rectum. With metastatic disease, adenopathy, hepatomegaly, or pulmonary signs may be present. Laboratory examination may reveal iron-deficiency anemia and electrolyte and liver function abnormalities.
Clinical Evaluation and Staging
Accurate staging provides crucial information about the location and size of the primary tumor in the rectum, and, if present, the size, number, and location of any metastases. Accurate initial staging can influence therapy by helping to determine the type of surgical intervention and the choice of neoadjuvant therapy to maximize the likelihood of resection with clear margins. In primary rectal cancer, pelvic imaging helps determine the depth of tumor invasion, the distance from the sphincter complex, the potential for achieving negative circumferential (radial) margins, and the involvement of locoregional lymph nodes or adjacent organs. The initial clinical evaluation and staging procedures may include the following:[7,18,19,20,21,22,23]
- Digital-rectal examination and/or rectovaginal exam and rigid proctoscopy to determine if sphincter-saving surgery is possible.[7,18,19]
- Complete colonoscopy to rule out cancers elsewhere in the bowel.
- Pan-body computed tomography (CT) scan to rule out metastatic disease.
- Magnetic resonance imaging (MRI) of the abdomen and pelvis to determine the depth of penetration and the potential for achieving negative circumferential (radial) margins, as well as to identify locoregional nodal metastases and distant metastatic disease.
- Endorectal ultrasound (ERUS) with a rigid probe or a flexible scope for stenotic lesions to determine the depth of penetration and identify locoregional nodal metastases.[19,21]
- Positron emission tomography (PET) to image distant metastatic disease.
- Measurement of the serum carcinoembryonic antigen (CEA) level for prognostic assessment and the determination of response to therapy.[22,23]