Apoptosis and cancer

What is apoptosis

Apoptosis is a process of programmed cell deaths (cell suicide) triggered by diverse internal and external signals. Apoptosis is an essential process by which our body eliminates old cells, abnormal cells, or damaged cells.

After a cell is stimulated by an apoptotic signal, the cell undergoes a sequence of organized degradation of cellular components characterized by membrane blebbing and cell shrinkage, condensation of chromatin, fragmentation of DNA, and engulfment of the dead cell by neighboring phagocytic cells.

Apoptosis is a tightly regulated process that plays a crucial role in maintaining our body’s homeostasis. There are many diseases associated with too much or too less apoptosis. Exaggerated apoptotic cell death is characteristic of stroke and neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis (ALS).

Acquired immune deficiency syndrome (AIDS) is characterized by too much apoptotic cell death of T-helper cells that play a critical in our body’s immune system. Too less or inhibited apoptosis has been identified in many malignancies and autoimmune disorders.

Role of apoptosis in cancer development

In general, cancer develops from a cell that has damage to its DNA. When DNA damage occurs in a cell, a tumor suppressor gene called p53 is activated and expressed into a tumor suppressor protein p53. The protein induces apoptosis of the damaged cell preventing it from becoming cancer cell.

This antitumor activity of p53 protein is completely lost or reduced if the p53 tumor suppressor gene is mutated or damaged by various environmental chemicals or agents, including carcinogenic chemicals containing in the cigarette smoking, radiation, or chemicals in workplaces, the cells can progress to cancer. Many existing and new anticancer treatments are based on stimulation of apoptotic pathways in cancer cells by which cancer cells undergo apoptotic cell death.

What is cancer

Cancer is characterized by uncontrolled growth, invasion and metastasis.

Cancer, or malignant neoplasm in medical term, is a class of diseases which is characterized by an uncontrolled cell growth, invasion and metastasis. Many different types of cancer arise from different types of cell in the body. The three characteristics are what all types of cancer have in common. Most cancers form solid lumps or masses of tissue called tumor (solid neoplasm, malignant tumor), but some do not (for example leukemia).

Uncontrolled Growth: Cancer cells grow out of control.

Human body is made up of about 100 trillion or 1014 cells. Normal cells grow, divide, and die in a tightly controlled manner. Normal cells become cancer cells because of defective DNA. When cells are damaged or genetically mutated for whatever reason and cannot be repaired through our body’s repair mechanism, a programmed cell death (apoptosis) occurs, removing the damaged cells and thus preventing their conversion into cancerous cells. However, when the apoptosis is broken down, the damaged abnormal cell can grow out of control and becomes cancer. All the new cancer cells will have the same damaged DNA as the first abnormal cell does.

Invasion: Malignant tumors invade nearby tissues and organs.

When tumors are confined to a spot, and do not invade the surrounding tissue or metastasize they are considered benign. Malignant cancer cells can invade surrounding tissue and grow to tumor destroying adjacent healthy tissues.

Metastasis: Cancer cells can spread to other parts of the body.

Cancer cells can break away from the tumor tissue (the primary tumor) and move through the body via the blood vessels or lymph systems, and be seeded within normal tissues and grow to tumor. The newly formed tumor is called the secondary tumors. The secondary tumor may then grow out of control, invade nearby tissues and organs, and spread (metastasize) again. Metastasis is probably the most lethal characteristic of a cancer, and is the most common cause of cancer-related death. Most tumors can metastasize.

The malignant properties of cancers differentiate them from benign tumors, which are self-limited, and do not invade or metastasize. Most cancers form a tumor but some, like leukemia, do not.



What is tumor?

A tumor is an abnormal mass of tissue or solid lesion formed by abnormal growth of cells.
The term tumor is not synonymous with cancer. Cancer is malignant by definition, which is characterized by an uncontrolled cell growth, invasion and metastasis.

Most cancers form abnormal mass of tissue or solid lesion, but some not, for example leukemia, a cancer of blood or bone marrow. Originally, the term tumor was used for all type of abnormal solid mass or generally swelling, benign or malignant. Accordingly, not all tumors are cancerous. A tumor can be benign or malignant. Benign tumor is not cancerous, and does not invade neighbor tissues or metastasize.



Neoplasm

Neoplasm is an abnormal mass of tissue or solid lesion formed by abnormal growth of cells (neoplasia/neoplastic). Neoplasm usually develops into tumor, and it can be benign or malignant. But in contemporary common and medical usage, solid neoplasm is used as a synonym for tumor. Some neoplasms do not develop into solid lump (tumor), for example leukemia.



Classification of cancers

Cancers are classified based on the type of cells that undergo uncontrolled growth.

Carcinoma

Carcinoma is a malignant tumor derived from cells in epithelial tissue. Epithelial tissue lines all the cavities, vessels and organs in the body. Carcinoma is the most common type of cancers including lung, breast, colon, and prostate cancer.

Adenocarcinoma

Adenocarcinoma is a type of carcinomas that originate in glandular, epithelial tissue. The epithelial cells in glandular tissue possess secretory properties and release their product into the bloodstream (such as hormones), into cavities in the body (such as gastric acid), or into the external environment (such as sweat, salivary, breast milk).

Sarcoma

Sarcoma is a malignant neoplasm (cancer) that is derived from connective or supportive tissue cells such as bone, cartilage, and muscle cells. Based on the type of tissue from which sarcoma develops, it is called osteosarcoma (bone cell), chondrosarcoma (cartilage cell) and leiomyosarcoma (smooth muscle). A soft tissue sarcoma is a very rare form of sarcoma which accounts for less than 1% of all cancers.

Lymphoma

Lymphoma is a cancer that arises from the lymphatic cells of the immune system, including lymphoma of B cells, T cells and natural killer (NK) cells. Lymphoma is a solid tumor of lymphoid cells, mostly B cells, whereas the closely related lymphoid leukemia affects only lymphocytes in the circulating blood and the bone marrow and usually does not form solid tumors.

Leukemia

Leukemia, also call blood cancer, is a cancer of cells in the bone marrow and blood. It is the most common cancer in children. Leukemia is characterized by a cancerous increase of abnormal blood cells and production retardation of healthy blood cells, resulting in many abnormal blood cells in the blood. The cells of the bone marrow can develop into different types of blood cell. In leukemia, the bone marrow cells which normally develop into white blood cells (leucocytes) are affected.

Myeloma

Myeloma is a cancer of blood cells called plasma cells. Plasma cells are one type of white blood cells that mainly found in the bone marrow and produce antibodies. When a plasma cell becomes cancerous, this abnormal cell multiplies out of control in the bone marrow, fill the bone marrow and prevent it from making other normal blood cells. The cancerous plasma cell can produce a tumor called plasmacytoma. When there is more than one plasmacytoma, it is called multiple myeloma.

Uterine cancer causes and risk factors

Uterine cancer, also called endometrial cancer, is the most common gynecologic cancer in the developed countries.

While the incidence and mortality rates of many common cancers have remained stable or decreased in the last decade, the rates for uterine cancer are still on the rise.

This rise is partly attributed to the epidemic increase in the prevalence of overweight and obesity, especially in the developed countries.

The most significant risk factors for uterine cancer include age, obesity and endometrial hyperplasia.


Age

Although uterine cancer can occur at any age, it is generally a disease of the middle-aged or elderly. Uterine cancer is quite rare in women under the age of 40.

The incidence rate rises steeply with age and the highest rate occurs in women in their 60s. Most cases of uterine cancer are diagnosed in women over the age of 50.


Overweight and obesity

Obesity is a significant risk factor for uterine cancer. Women of an excessive overweight are 2 to 3 times more likely to develop uterine cancer than women of a normal weight.

Fat tissue can convert certain hormones into estrogen. Excessive fat tissue raises the levels of circulating estrogens, which enhances the growth of endometrial cells, resulting in higher risk of uterine cancers.

Uterine cancer was the first cancer which was recognized as being related to obesity. The incidence rates of uterine cancers are much higher in the developed countries, where obesity rates are higher and rising rapidly.

Morbid obesity not only increases the risk of developing uterine cancer, it also increases the risk of dying from the disease.

Read more about obesity and uterine cancer


Endometrial hyperplasia

Endometrial hyperplasia is a benign condition characterized by an excessive proliferation of the lining cells of the uterus (womb), thickening the lining of the womb.

In most cases it is a mild or simple hyperplasia that goes away on its own or can be treated easily.

Sometimes uterine hyperplasia can get worse, leading to atypical changes of the lining of the womb.

Atypical hyperplasia is not a cancer, but is a kind of precancerous growth that increases the risk of developing uterine cancer.


Polycystic ovarian syndrome

Polycystic ovarian syndrome (PCOS), also called ovarian hyperthecosis or sclerocytic ovary syndrome, is a condition where cysts grow in the ovary.

Women with polycystic ovarian syndrome have a hormone imbalance between estrogen and progesterone levels, causing irregular periods, lack of periods, and fertility problems.

Women with PCOS are more likely to be overweight or obese and to have a higher estrogen level, diabetes and high blood pressure, which in turn increase the risk of uterine cancer.


Hereditary nonpolyposis colon cancer (HNPCC)

People with a genetic disorder called hereditary nonpolyposis colon cancer (HNPCC) or Lynch syndrome have a very high risk of getting colon cancer and a high risk of uterine cancer.

Women with this disorder tend to develop uterine cancer at a younger age than women in the general population.


Pregnancy

Women who have never been pregnant are more likely to develop uterine cancer than women who have had child.

During the pregnancy estrogen levels are low and progesterone levels are high, decreasing the risk of uterine cancer. Studies found that having three or more children can lower the risk up to two thirds.


Hormon replacement therapy (HRT)

Hormon replacement therapy (HRT) is used by many women to treat the symptoms of menopause.

Estrogen therapy can reduce the symptoms, such as hot flashes, and prevent bone losses (osteoporosis).

However, estrogen only therapy can lead to a hormone imbalance between estrogen and progesterone, which increases the risk of uterine cancer.

A combination hormone therapy, using estrogen along with progesterone, does not increase the risk of uterine cancer, but slightly increases the risk of breast cancer.


Graphical cancer statistics – Uterine cancer



Gallbladder cancer causes and risk factors

Gallbladder cancer is a relatively rare cancer, accounting for about 1% of all cancer cases (excl. non-melanoma skin cancer) worldwide. Unlike many common cancers, gallbladder cancer is more common among women than among men. The incidence varies greatly in different parts of the world.

Gallstones are considered the most important risk factor for gallbladder cancer. About 80-90% of gallbladder cancers are attributed to gallbladder cancer.

Obese people are more likely to develop gallbladder cancer. They are also more like to have gallstones, the major risk for gallbladder cancer.

Gallstones and inflammation of the gallbladder

Gallstones are hard, rock-like lumps that form in the gallbladder from cholesterol and other substances. Gall stones are the most important risk factor for gallbladder cancer. About 80% of gallbladder cancer patients have gallstones at the time of cancer diagnosis.

Gallstones can cause chronic inflammation of the gallbladder. Gallstones are very common, but most people with gallstones or inflamed gallbladder do not develop gallbladder cancer.

Gender and Age

Gallbladder cancer is more common among women than among men. Gallbladder cancer occurs more frequently in older people. Most people diagnosed with gallbladder cancer are older than 70. Gallbladder cancer is quite uncommon in people under the age of 60.

Porcelain gallbladder

Porcelain gallbladder is a condition in which calcium deposits build up on the inside wall of the gallbladder. Porcelain gallbladder may be caused by long-term gallbladder inflammation and increase the risk of gallbladder cancer. An extensive calcification of the gallbladder wall makes the gallbladder brittle.

Obesity

Obesity increases the risk of gallbladder cancer. The exact mechanism by which the obesity may increase the risk of gallbladder cancer is unknown. Obesity may increase the risk of gallstones, which, in turn, increase the risk of gallbladder cancer. The association between gallbladder cancer and obesity is stronger for women than for men.

Another possible mechanism for the association may include changes in endogenous hormones balance in overweight and obese individuals. The reason for the stronger association in women is unknown.

Race and ethnicity

The incidence of gallbladder cancer varies greatly among different racial/ethnic groups and in different parts of the world. In the United States, the incidence of gallbladder cancer is highest among Native Americans and Hispanic/Latinos. They are also more likely to have gallstones than other racial/ethnic groups.

Worldwide, gallbladder cancer is more common in some Asian and South American countries, including Northern India, Pakistan, Korea, Japan, Mexico, Bolivia, and Chile.

Family history

People with a family history of gallbladder cancer are more likely to develop the cancer. As gallbladder cancer is a fairly rare disease, the risk is still very low.

Gallbladder polyps

A gallbladder polyps is a growth on the surface lining of the inner gallbladder wall. It is not cancerous but larger polyps can become cancerous. If polyps is larger than 1 centimeter, you may be advised to remove the gallbladder.


Graphical cancer statistics – gallbladder cancer



Lung cancer causes and risk factors

Smoking

Smoking is the single most important and preventable risk factor and the main cause of lung cancer. About 9 out of 10 cases of lung cancer are caused by smoking.

In the United States, smoking-attributable mortality (SAM) account for about 90% and 72% of the total lung cancer deaths in men and women, respectively. Most patients with small cell lung cancer (SCLC) are smokers. SCLC is quite rare in people who have never smoked.

SCLC is more aggressive than NSCLC. It grows and spreads (metastasize) very quickly. Most patients with SCLC are diagnosed after the cancer has already spread to other parts of the body.


Exposure to radon

Radon is a radioactive gas that generated form the breakdown of uranium, which is naturally present in soils and rocks. Exposure to radon is the second leading cause of lung cancer in the US. About 21,000 lung cancer deaths are estimated to be attributable to radon exposure in the US each year.


Asbestos exposure

Chronic exposure not only increases the risk of mesothelioma, it also increases the risk of lung cancer, and other non-malignant lung disorders such as asbestosis, pleural plaques, and diffuse pleural thickening.


Exposure to cancer-causing chemicals

People who have been exposed to certain cancer-causing substances (carcinogens) in the workplace are more likely to develop lung cancer. They include asbestos, polycyclic aromatic hydrocarbons, diesel exhausts, nickel-chromium compounds, metal dust and fumes, and crystalline silica. Exposure to occupational carcinogens is relatively rare cause of lung cancer and is an important preventable cause of lung cancer.


Family history

People with close relatives (brothers, sisters, parents) who have had lung cancer may have a higher risk of developing lung cancer. It is not clear whether the increased risk is due to an inherited faulty gene or other risk factors such as smoking or diets.


Radiation therapy to the lungs

People who have received radiation therapy to the chest to treat other types of cancer, particularly to treat Hodgkin’s lymphoma and breast cancer, are at a slightly increased risk of developing lung cancer.

However, studies found that the increased risk of lung cancer was mainly attributable to the combined effect of the therapy and smoking or smoking alone (87.4%) and only 9.6% were due to the treatment alone, underscoring the importance of smoking cessation for Hodgkin’s lymphoma patients who have had radiation therapy.


Facts about smoking and lung cancer risk

  • If you smoke 1-14 cigarettes a day, your risk of dying from lung cancer is about eight times higher. It is about 25 times, if you smoke 25 or more cigarettes a day.
  • Starting smoking at a young age greatly increases the risk of lung cancer.
  • The risk becomes higher the more and the longer you smoke.
  • Passive smoking or second-hand smoking also increases the risk of lung cancer.
  • Stopping smoking lowers your risk of lung cancer regardless of your age and length of time you have been a smoker.
  • As soon as you stop smoking, your risk of developing lung cancer starts to go down. After about fifteen years from stopping smoking, your risk of developing lung cancer becomes similar to that of a non-smoker.
  • Reference

    Sethi et al. Radon and lung cancer. Clin Adv Hematol Oncol (2012) 10: 157-164.

    McCormack et al. Estimating the asbestos-related lung cancer burden from mesothelioma mortality. BJC (2012)106: 575-584.

    Henderson et al. After Helsinki: a multidisplinary review of the relationship between asbestos exposure and lung cancer, with emphasis on studies published during 1997-2004. Pathology (2004) 36: 517-550.

    Travis et al. Lung cancer following chemotherapy and radiotherapy for Hodgkin’s disease. J Natl Cancer Inst (2002)94:182–92.



    Graphical cancer statistics – Lung cancer



    Lung cancer signs and symptoms

    The most common symptom of lung cancer is a persistent, painful cough.

    Many lung cancers do not develop symptoms in the early stages. As the cancer grows, the most common lung cancer symptom is a persistent, painful cough. Other common symptoms of lung cancer include:

    • Coughing up blood
    • Blood-stained sputum
    • Pain in the chest or shoulder when breathing or coughing
    • Lung infection (pneumonia) or bronchitis
    • Hoarseness in the voice
    • Shortness of breath wheezing
    • Difficulty swallowing
    • Changes in the shape of fingers and nails (finger clubbing)
    • Loss of appetite or unintentional weight
    • Fatigue


    Paraneoplastic symptoms

    Some lung cancers (most commonly small cell lung cancer) produce hormones or hormone-like substances that get into the bloodstream and cause symptoms in other parts of the body called paraneoplastic symptoms or paraneoplastic syndrome. Because these symptoms affect other organs and do not seem to be related to lung cancer, they can easily be considered to be caused by a disease other than lung cancer. These symptoms may include:

    • Blood clots (thrombosis)
    • Muscle weakness
    • Drowsiness or dizziness
    • Fatigue
    • Nausea or vomiting
    • Loss of appetite
    • Vision problems

    These symptoms may be caused by lung cancer, but are also caused by other health problems. However, if you have one or more these symptoms, it is important to talk with a doctor.


    Graphical cancer statistics – Lung cancer



    Mesothelioma causes and risk factors

    The single most important risk factor for mesothelioma is exposure to asbestos. Most cases of malignant mesothelioma (also known as asbestos cancer) are caused by previous exposure to asbestos in the workplace.

    However, not all cases of mesothelioma are associated with asbestos exposure. The tumor occurs in only 10% to 20% of people who have been heavily exposed to asbestos, and about 20% of patients have no history of asbestos exposure.

    Asbestos exposure

    Asbestos is a term for a group of naturally occurring fibrous minerals. It is heat and fire resistant, and has ideal tensile strength and resilience for construction and insulation purposes.

    Asbestos has been used as insulating and coating material in manufacturing a wide variety of industrial and household products through most of the 20th century.

    By the middle of the 20th century, it became evident that asbestos exposure increased the risk of for several lung diseases such as pleural effusions, asbestosis, and mesothelioma.

    The link between asbestos exposure and mesothelioma was first established when Wagner et al. (1960) published the study on the occurrence of mesothelioma in people working in asbestos mines in Cape Province, South Africa.

    The other high-risk occupations include asbestos textile workers, insulation workers, plumbers, electricians, painters, construction workers, and ship building/maintenance workers.

    Very short occupational asbestos exposure for as little as one or two months can result in malignant mesothelioma.

    Types of asbestos

    The majority of asbestos fibers are either amphibole or serpentine. The serpentine fibers are considered less carcinogenic than the amphibole fibers. Chrysotile is the main type of serpentine and by far the most frequently used asbestos worldwide (about 95% of world asbestos production and use).

    People believed that amphibole asbestos caused mesothelioma, but not chrysotile. The increased risk of mesothelioma in the chrysotile industry was attributed to contamination by highly carcinogenic amphibole fibers.

    However, numerous studies over the past decades have clearly demonstrated the strong association between malignant mesothelioma and all types of asbestos, including chrysotile.

    Because chrysotile is by far the most common type of asbestos produced and used, chrysotile asbestos is the overwhelming asbestos exposure causatively related to malignant mesothelioma.

    Asbestos and mesothelioma

    Asbestos fibers most commonly affect the outer lining of the lungs and chest cavity but can also affect the lining of the abdominal cavity, and very rarely the lining of the heart.

    Asbestos fibers are insoluble in aqueous physiological fluids. When inhaled, the fibers can cause physical damages in the tissues of the respiratory track, leading to the development fibrosis and plaques.

    When asbestos fibers are breathed in, they can reach the pleura lining of the lungs and chest wall. These fibers can be phagocytosed into mesothelial cells of the pleura and initiate several oncogenic transformations, and eventually cause mesothelioma.

    Asbestos-related damages may increase the production of reactive oxygen species (ROS) that can cause oxidative DNA damages in the mesothelial cells, transforming them into malignant cancer cells.

    If asbestos fibers are ingested (swallowed), they can reach the abdominal cavity and can damage the mesothelial cells in the lining of the abdominal cavity (peritoneum). It often takes many years after being exposed to asbestos for mesothelioma to develop.

    Pericardial mesothelioma and asbestos exposure

    While there is a strong association between asbestos exposure and two mayor types of mesothelioma, pleural and peritoneal mesothelioma, the role of asbestos exposure in the development of pericardial mesothelioma is not obvious.

    Primary pericardial mesotheliomas starts in covering around the heart and are extremely rare, accounting for less than 1% of all mesothelioma cases.

    Age and gender

    Most cases of mesothelioma occur in older people over age 60. It is quite rare in younger people under age 45. Mesothelioma is about 3 times more common in men than in women.

    This is probably because men have been more likely to be exposed to asbestos in their workplace than women.

    Non-asbestos mesothelioma

    Although there is a strong association between occupational asbestos exposure and the development of malignant mesothelioma, and most patients with mesothelioma have been exposed to asbestos, about 20% of patients have no history of asbestos exposure.

    Simian virus 40

    Simian virus 40 or SV40 is a monkey polyoma virus discovered as a contaminant in the early poliovirus vaccines produced in the monkey kidney cells and used in the US and Europe from 1955 to 1963.

    Several animal studies showed that SV40 virus can cause mesothelioma, alone or with asbestos exposure.

    A study showed that hamsters developed mesotheliomas (100%) after direct intrapleural inoculation of SV40. The etiologic connection between SV40 and human mesothelioma has not been proven yet.

    Radiation therapy

    Radiation therapy is considered as a possible cause of mesothelioma. Several studies showed that patients with cancers other than mesothelioma developed mesothelioma after radiation therapy without any obvious asbestos exposure.

    Reference

    Mensi et al. Pericardial mesothelioma and asbestos exposure. Int J Hyg Envir Heal (2011) 214: 276-279.

    Shah et al. Human exposure to SV40. Am J Epidemiol (1976) 103: 1-12.

    Cicala et al. SV40 induces mesothelioma in hamsters. Am J Pathol (1993) 142: 1524-1533.

    Tward et al. The risk of secondary malignancies over 30 years after the treatment if non-Hodgkin lymphoma. Cancer (2006) 107: 108-115.

    Travis et al. Second cancers among 40,576 testicular cancer patients. J Natl Cancer Inst (2005) 97: 1354-1365.

    Deutsch et al. An association between postoperative radiotherapy for primary breast cancer in 11 National Surgical Adjuvant Breast and Bowel Project (NSABP) studies and the subsequent appearance of pleural mesothelioma. Am J Clin Oncol (2007) 30: 294-296.


    Read more about asbestos-related diseases



    Graphical cancer statistics – Mesothelioma



    Mesothelioma signs and symptoms

    Mesothelioma is a cancer that develops in the tissues lining the inside of the chest and abdomen, the lungs, or rarely the heart. The cells in the tissues are called mesothelial cells and the lining formed is called mesothelium. Mesothelioma is a cancer of mesothelial cells.

    Many mesotheliomas usually do not develop symptoms in the early stages. Symptoms or signs of mesothelioma are quite vague and nonspecific especially in the early stages. The symptoms vary depending on the site of the mesothelioma. There are two main types of mesothelioma, pleural and peritoneal mesothelioma.

    Pleural mesothelioma starts in the chest, in the tissue surrounding the lung (pleura). The pleural membrane is composed of the inner layer that covers the lungs and the outer layer that lines the inner chest wall and upper diaphragm surfaces. The area between the two layers is the pleural space filed with serous fluid that is important for lubricating the inner pleural surface during expansion and contraction of the lung.

    Pleural mesothelioma is the most common form of mesothelioma, accounting for about 3 out of 4 mesotheliomas. Malignant pleural mesothelioma is one of the most difficult forms of cancer to cure. The median survival of patients is estimated to be 7 to 17 months after diagnosis. Most of the remaining cases are peritoneal mesothelioma that starts in the abdomen, in the tissue lining the abdominal cavity (peritoneum).

    Both types of mesothelioma can cause non-specific symptoms such as loss of appetite, weight loss, feeling tired or fatigue, fever, and night sweating.

    Pleural mesothelioma

    When mesothelioma grows in the pleura (outer lining of the lung), it leads to thickening of the pleura, pressing inwards on the lung. The common symptoms of pleural mesothelioma include:

  • Pain in the chest wall
  • Shortness of breath (dyspnea)
  • Painful breathing
  • Persistent cough
  • Difficulty in swallowing
  • Loss of appetite and unintentional weight loss
  • Feeling tired and weak
  • Symptoms of late stage malignant pleural mesothelioma include pneumonia (lung infection).

    Peritoneal mesothelioma

    When mesothelioma grows in the tissue lining the abdominal cavity (peritoneum), it leads to thickening of the lining of the abdomen and fluid can collect in the abdomen (ascites). The common symptoms of peritoneal mesothelioma include:

  • Pain in the abdomen
  • Swelling or lumps in the abdomen
  • Fluid in the abdominal cavity
  • Nausea and vomiting
  • Kidney cancer causes and risk factors

    What exactly causes kidney cancer is unknown. However, people with certain risk factors may have higher risk of developing kidney cancer than others.

    Smoking and kidney cancer

    People who smoke have a higher risk of developing kidney cancer.

    Smoking is a well-established risk factor for kidney cancer and there exist a causative relationship between smoking and kidney cancer.

    The cancer-causing chemicals (carcinogens) in the tobacco smoke get into the bloodstream. They are filtered out of the blood by the kidney and end up in the urine. The tissues in the kidney come in contact with the chemicals which may induce DNA damage.

    In addition, it is hypothesized that the risk of kidney cancer increases through chronic tissue hypoxia resulting from carbon monoxide exposure, and via smoking-related disorders such as chronic obstructive pulmonary disease. About a third of kidney cancers are thought to be caused by smoking.

    Smoking not only increases the risk of developing kidney cancer, it also promotes cancer progression and is responsible for more aggressive, advanced disease. The association between smoking and kidney cancer is stronger in men than in women. In the US, about 38% of kidney cancer deaths in men and 8% in women are attributed to smoking.

    Obesity

    Obese people are at a higher risk of developing kidney cancer. Elevated body mass index (BMI) has consistently found to be associated with renal cell carcinoma (RCC). The association between BMI and RCC is stronger in women than in men.

    Body Mass Index (BMI)

    Body mass index is a number calculated using person’s height and weight. It provides a reliable estimation of how much body fat you have. BMI (unit: kg/m2) is classified:

  • 18.5 or less: Underweight
  • 18.5 to 24.9: Normal weight
  • 25 to 29.9: Overweight
  • 30 to 39.9: Obesity
  • 40 or greater: Morbid obesity
  • Age and gender

    As with many other cancers, age is the most important risk factor for kidney cancer. Although kidney cancer can occur at any age, most cases occur in people over the age of 50. It is extremely rare in younger people under 40.

    Kidney cancer is more common in men than in women. This may be, in part, because men are more likely to smoke and to be exposed to cancer-causing chemicals in their workplace. The life time risk of developing kidney cancer is about 1 in 51 for men and 1 in 84 for women in the

    Hypertension

    People who have high blood pressure have an increased risk of kidney cancer. Hypertension has been found to be associated with an increased risk of renal cell carcinoma (RCC) in both men and women.

    Chemicals in workplace

    Some people are exposed to cancer-causing chemicals in their workplace. These chemicals include asbestos, some herbicides, cadmium, petroleum, and some organic solvents.

    Family history of kidney cancer

    In a few cases, kidney cancer is associated with an inherited gene fault. People with family members who have had kidney cancer have an increased risk of the disease.

    Kidney dialysis

    People who have advanced kidney disease and undergo long-term kidney dialysis have a higher risk of kidney cancer.

    Hypoxia

    Hypoxia is a condition in which oxygen concentrations in the whole body or a part of the body are below physiological level due to the reduction of oxygen supply.


    Graphical cancer statistics – Kidney cancer



    Esophageal cancer causes and risk factors

    Although the exact causes of esophageal cancer are unknown, there are several risk factors that can increase the risk of developing esophageal cancer. Smoking is the most important risk factor of esophageal cancer.

    Esophageal cancer and smoking

    Tobacco use is well recognized as the main risk factor for esophageal cancer particularly in the western countries. Smoking increases the risk of the two main types of esophageal cancer, squamous cell carcinoma (SCC) and adenocarcinoma. Smoking cigarettes, cigars and pipes all increase esophageal cancer risk.

    Barrett’s esophagus is a major risk factor for esophageal cancer. Smoking increases the risk of progression of Barrett’s esophagus to esophageal cancer.

    Smoking significantly increases the risk of lung metastasis from esophageal cancer. In the US, about 72% of deaths from esophageal cancer in men and 56% in women are attributed to smoking.

    Read more about esophageal cancer and smoking:

    Esophageal cancer and alcohol drinking

    Heavy alcohol drinking increases the risk of squamous cell carcinoma (SCC) of the esophagus. If you drink heavily and smoke, the risk increases synergistically, i.e., the combined risk is greater than the sum of the risk of drinking and the risk of smoking.

    Gastroesophageal reflux

    Gastroesophageal reflux disease (GERD), also called gastric reflux disease or acid reflux disease, is a condition in which gastric acid flows backward into the esophagus.

    GERD is the most common cause of esophageal adenocarcinomas. The reflux may cause symptoms such as heartburn or pain in the chest, but some people don’t have symptoms.

    Smoking and obesity increase the risk of GERD. Chronic, untreated acid reflux disease can develop into Barrett’s esophagus, which is the major known risk factor for esophageal adenocarcinoma.

    Barrett’s esophagus

    If the acid reflux continues for a long time, it can cause cell changes in the lining of the lower part of the esophagus near the stomach.

    Barrett’s esophagus is a condition in which the cells lining the esophagus (squamous cells) have become changed and replaced with glandular cells that look like the cells lining the stomach.

    The glandular cells can become more abnormal and then cancerous. People with Barrett’s esophagus are much more likely to develop adenocarcinoma of the esophagus.

    Age and gender

    Age is one of the main risk factors for esophageal cancer. Although esophagus cancer can occur at any age, most cases are diagnosed in people over the age of 60. In the US, only about 2.5% of esophageal cancers are diagnosed in people younger than 45.

    Esophageal cancer is much more common in men than in women. In the US, men are nearly four times more likely to develop esophageal cancer than women. The life time risk of developing esophageal cancer is about 1 in 127 for men and 1 in 417 for women in the US.

    Read more about esophageal cancer and age


    Esophageal cancer and obesity

    Obesity increases the risk of adenocarcinoma of the esophagus. This may be because obese people are more likely to have esophageal reflux disease which is the main risk factor for adenocarcinoma of the esophageal cancer.


    Graphical cancer statistics – Esophageal cancer