A 55-year-old man presents with increasing fatigue, 15-pound weight loss, and a microcytic anemia. Colonoscopy identifies a mass in the ascending colon, and biopsy specimens reveal well-differentiated colorectal cancer (CRC). He undergoes surgical resection and is found to have high-risk stage III CRC with five positive lymph nodes. After surgery, he feels entirely well with no symptoms. Of note, he has no other comorbid illnesses. What is this patient’s prognosis? Should he receive adjuvant chemotherapy? The patient receives a combination of 5-fluorouracil (5-FU), leucovorin, and oxaliplatin as adjuvant therapy. One week after receiving the first cycle of therapy, he experiences significant toxicity in the form of myelosuppression, diarrhea, and altered mental status. What is the most likely explanation for this increased toxicity? Is there any role for genetic testing to determine the etiology of this level of toxicity?
In 2014, approximately 1.6 million new cancer cases will be diagnosed in the USA, and nearly 580,000 individuals will die from this disease. Cancer is the second most common cause of death in the United States, accounting for 1 in 4 deaths. It is a disease characterized by a defect in the normal control mechanisms that govern cell survival, proliferation, and differentiation. Cells that have undergone neoplastic transformation usually express cell surface antigens that may be of normal fetal type, and they may display other signs of apparent immaturity, and may exhibit qualitative or quantitative chromosomal abnormalities, including various translocations and the appearance of amplified gene sequences. It is now well established that a small subpopulation of cells, referred to as tumor stem cells, reside within a tumor mass. They retain the ability to undergo repeated cycles of proliferation as well as to migrate to distant sites in the body to colonize various organs in the process called metastasis. Such tumor stem cells thus can express clonogenic (colony-forming) capability, and they are characterized by chromosome abnormalities reflecting their genetic instability, which leads to progressive selection of subclones that can survive more readily in the multicellular environment of the host. This genetic instability also allows them to become resistant to chemotherapy and radiotherapy. The invasive and metastatic processes as well as a series of metabolic abnormalities associated with the cancer result in tumor-related symptoms and eventual death of the patient unless the neoplasm can be eradicated with treatment.
The incidence, geographic distribution, and behavior of specific types of cancer are related to multiple factors, including sex, age, race, genetic predisposition, and exposure to environmental carcinogens. Of these factors, environmental exposure is probably most important. Exposure to ionizing radiation has been well documented as a significant risk factor for a number of cancers, including acute leukemias, thyroid cancer, breast cancer, lung cancer, soft tissue sarcoma, and basal cell and squamous cell skin cancers. Chemical carcinogens (particularly those in tobacco smoke) as well as azo dyes, aflatoxins, asbestos, benzene, and radon have ...