Cancer

• 1. Introduction

  ›

  Cancer takes its name from a crab. The ancient Greek word karkinos meant both crab and tumor, and Greek physicians like Hippocrates and Galen saw the resemblance in solid tumors whose swollen veins fanned out like a crab's legs. Galen put it plainly. Cancer of the breast, he said, was so called because of the fancied resemblance to a crab given by the lateral prolongations of the tumor and the adjacent distended veins. The word entered English in its modern medical sense around 1600.

  More than 100 types of cancer affect humans, yet they share one rebellious trait. Cells that should grow on command instead grow without it. In 2019, annual cases reached 23.6 million and deaths reached 10 million worldwide. So what makes a single cell turn against the body that built it. Why does smoke, sunlight, or an old infection tip the odds. And why, after thousands of years of crab metaphors, does so much of the danger still come down to the order in which mutations stack up. The chapters ahead follow the disease from a single corrupted gene to the global ledger of survival.

• 2. The Cellular Rebellion

  ›

  Cancer is fundamentally a disease of tissue growth regulation. For a normal cell to become a cancer cell, the genes that govern growth and differentiation must change. Those genes fall into two camps. Oncogenes push cells to grow and reproduce. Tumor suppressor genes hold cell division and survival in check. Cancer arises when oncogenes are switched on inappropriately or tumor suppressors are silenced, and usually it takes changes in multiple genes to complete the transformation.

  Replication of DNA inevitably produces some errors. Cells carry elaborate error correction, and a badly damaged cell can self-destruct through programmed cell death, called apoptosis. When those safeguards fail, the mutation survives and passes to daughter cells. The process is self-amplifying. A flaw in the error-correcting machinery makes a cell accumulate more flaws. A mutation in an oncogene speeds reproduction. The loss of a tumor suppressor disables apoptosis and renders the cell effectively immortal.

  Tumor cells display the six hallmarks of cancer. They grow without proper signals, keep growing despite contrary signals, dodge programmed cell death, divide without limit, recruit new blood vessels, and invade tissue to form metastases. The progression from a normal cell to a detectable mass passes through multiple steps known as malignant progression.

  Mutations are not the whole story. Epigenetic alterations, which change how the genome behaves without changing the DNA sequence, occur frequently in cancers. One study of colon cancer found 147 hypermethylated and 27 hypomethylated genes, with 10 hypermethylated in 100% of the cancers examined. Alterations that quiet DNA repair genes may matter most, since they let damage and further mutation accumulate. An average breast or colon cancer carries about 60 to 70 protein-altering mutations, of which only three or four are driver mutations and the rest are passengers.

• 3. What Tips The Odds

  ›

  Some 90 to 95% of cancers trace to environmental and lifestyle factors, not inherited genes. Environmental here means anything not inherited, including economic and behavioral factors, not merely pollution. The major contributors to cancer death include tobacco at 25 to 30%, diet and obesity at 30 to 35%, infections at 15 to 20%, and radiation up to 10%. Psychological stress does not appear to trigger cancer, though it may worsen outcomes in those who already have it.

  Tobacco smoke causes 90% of lung cancer and carries over fifty known carcinogens, including nitrosamines and polycyclic aromatic hydrocarbons. It is responsible for about one in five cancer deaths worldwide and one in three in the developed world. Lung cancer death rates in the United States have tracked smoking patterns, with declines in male death rates since 1990 following the drop in smoking that began in the 1950s.

  Diet, inactivity, and obesity drive up to 30 to 35% of cancer deaths, and more than half of the dietary effect comes from overnutrition rather than too few vegetables. A UK study of over 5 million people tied higher body mass index to at least 10 cancers and roughly 12,000 cases a year there. Specific foods carry specific risks. A high-salt diet is linked to gastric cancer, common in Japan, while colon cancer is more common in the United States. Immigrant cancer profiles come to mirror their new country, often within one generation.

  Around 18% of cancer deaths worldwide are tied to infection, ranging from 25% in Africa to under 10% in the developed world. In 2018, infection caused 2.2 million cases, led by Helicobacter pylori at 810,000, human papillomavirus at 690,000, hepatitis B at 360,000, and hepatitis C at 160,000. All four can be vaccinated against or treated. HIV does not directly cause cancer, but the immune deficiency it creates can raise risk from other infections, sometimes up to several thousandfold.

  Inherited genetics account for the remaining 5 to 10% of cancers. Fewer than 0.3% of people carry a high-impact mutation. Certain BRCA1 and BRCA2 mutations carry a more than 75% risk of breast and ovarian cancer. Some DNA repair defects, such as p53 mutations, ensure a 100% lifetime chance of cancer, yet such germline mutations cause only about 1% of cases.

• 4. The Body Betrayed

  ›

  When cancer begins, it produces no symptoms. Signs appear only as the mass grows or ulcerates, and few of them are specific. Many overlap with other conditions, which is why cancer can be considered a great imitator. The risk of suicide in people with cancer is approximately double.

  Local symptoms follow the tumor's location. Lung cancer can block the bronchus and cause cough or pneumonia. Esophageal cancer narrows the esophagus and makes swallowing painful. Colorectal cancer can obstruct the bowel. Ulceration brings bleeding, from coughing up blood in lung cancer to blood in the urine in bladder cancer. The initial tumor is usually painless, even when advanced cancer brings localized pain.

  Systemic symptoms reflect the body's whole-system response. Fatigue, unintentional weight loss, and skin changes are common, and some cancers drive a state of ongoing muscle loss known as cachexia. Hodgkin's disease, leukemias, and liver or kidney cancers can cause persistent fever. Some symptoms come from hormones the tumor itself produces, called paraneoplastic syndromes, such as hypercalcemia, which can cause altered mental state, constipation, and dehydration.

  Metastasis is the spread of cancer to other locations, and most cancer deaths are due to cancer that has metastasized. The original growth is the primary tumor; the offshoots are metastatic tumors. Almost all cancers can metastasize, traveling through the blood or lymphatic system in steps that run from local invasion to extravasation and proliferation in new tissue. Different cancers favor different destinations, but the most common sites are the lungs, liver, brain, and bones.

• 5. Reading The Disease

  ›

  A definitive cancer diagnosis requires a pathologist to examine a tissue sample. Signs, symptoms, and screening can raise suspicion, but only a biopsy confirms it. Investigation commonly includes blood tests, X-rays, contrast CT scans, and endoscopy, and the biopsy reveals the proliferating cell type, its histological grade, and its genetic abnormalities. Cytogenetics and immunohistochemistry add molecular detail such as mutations and fusion genes, all of which guide prognosis and treatment.

  Cancers are classified by the cell they resemble, which is presumed to be their origin. Carcinomas come from epithelial cells and include nearly all cancers of the breast, prostate, lung, pancreas, and colon. Sarcomas arise from connective tissue like bone, cartilage, and fat. Lymphoma and leukemia come from blood-forming cells. Germ cell tumors come from pluripotent cells, usually in the testicle or ovary, and blastomas come from immature precursor cells.

  The naming follows a logic of root and suffix. The organ or tissue of origin supplies the root, and carcinoma, sarcoma, or blastoma supplies the ending. A cancer of liver epithelial cells is a hepatocarcinoma, while one from fat cells is a liposarcoma. Benign tumors take the suffix oma, so a benign smooth-muscle tumor is a leiomyoma, commonly called a fibroid in the uterus. Confusingly, melanoma and seminoma are malignant despite that ending.

• 6. The Arsenal

  ›

  Surgery is the primary treatment for most isolated, solid cancers. In localized disease it removes the entire mass and sometimes the nearby lymph nodes, and for some cancers that alone eliminates the disease. Surgery is also central to diagnosis and staging, since biopsies are usually required.

  Chemotherapy treats cancer with cytotoxic drugs in a standardized regimen, killing the rapidly dividing cells that define most cancers. Combination therapy, using several drugs together, has proven more effective than a single drug for metastasized breast cancer. Targeted therapy, a form of chemotherapy, attacks specific molecular differences between cancer and normal cells. The first targeted therapies blocked the estrogen receptor to slow breast cancer, and Bcr-Abl inhibitors now treat chronic myelogenous leukemia.

  Radiation therapy damages the DNA of cancerous tissue, causing mitotic catastrophe. Shaped beams aimed from multiple angles converge on the tumor to spare healthy tissue, and radiation is used in about half of cases. For painful bone metastasis it brings relief in about 70% of patients. Yet radiation after surgery for brain metastases has not improved overall survival compared with surgery alone.

  Newer and gentler approaches widen the arsenal. Immunotherapy, which stimulates the immune system to fight cancer, has come into use since 1997 through monoclonal antibodies, checkpoint therapy, adoptive cell transfer, and CAR T cells. Laser therapy uses high-intensity light to shrink or destroy superficial tumors and is more precise than surgery, with less bleeding and scarring. Palliative care runs alongside all of this. Its goal is quality of life, and unlike hospice it does not require stopping treatment. It is indicated for patients with a prognosis of less than 12 months even with aggressive treatment.

  Against these stand complementary and alternative treatments, most of which have never been tested in clinical trials. The cancer researcher Andrew J. Vickers argued that the word unproven is too kind. It is time to assert, he said, that many alternative cancer therapies have been disproven.

• 7. The Global Ledger

  ›

  In 2018, the world saw 18.1 million new cancer cases and 9.6 million deaths, making cancer responsible for almost one in six deaths. About 20% of males and 17% of females will develop cancer, while 13% of males and 9% of females will die from it. The total economic cost of cancer has been estimated at US$1.16 trillion per year. As of 2020, the deadliest forms were lung cancer at 1.8 million, colorectal at 916,000, liver at 830,000, stomach at 769,000, and breast at 685,000.

  Survival depends on cancer type and the stage at diagnosis. The average five-year survival rate in the United States is 66% across all ages, while children under 15 in the developed world average 80%. Once cancer metastasizes the outlook worsens sharply, and about half of patients treated for invasive cancer die of it or its treatment. Survivors face a second primary cancer at about twice the rate of those never diagnosed.

  Age is the single most significant risk factor. Most invasive cancers strike people over 65, and the researcher Robert A. Weinberg observed that if we lived long enough, sooner or later we all would get cancer. Some slow-growing cancers are so common that autopsies in Europe and Asia found up to 36% of people carrying undiagnosed, harmless thyroid cancer, and 80% of men developing prostate cancer by age 80. Childhood cancer tells a different story. Leukemia accounts for 34% of cases, brain tumors 23%, and lymphomas 12%, and death from childhood cancer in the United States fell by half between 1975 and 2010.

  Prevention may be the most powerful lever of all. Around 40% of cancer can be prevented by avoiding or eliminating risk factors, and prevention is more cost-effective than treatment. The Montreal Protocol, signed in 1987 to limit ozone-damaging chemicals, is expected to prevent 11 million cases of melanoma in the United States by 2100, a reminder that some of the strongest defenses against cancer are written into international treaties rather than prescriptions.