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Genes and human disease

Genes and noncommunicable diseases

Most diseases involve many genes in complex interactions, in addition to environmental influences. An individual may not be born with a disease but may be at high risk of acquiring it. This is called as genetic predisposition or susceptibility. The genetic susceptibility to a particular disease due to the presence of one or more gene mutations, and/or a combination of alleles need not necessarily be abnormal.

WHO's department of Noncommunicable Diseases and Mental Health (NMH) has done extensive work on major noncommunicable diseases, like cancer, diabetes, cardiovascular disease, asthma, and some mental illnesses. In some cases, such as cancer, individuals are born with genes that are altered by lifestyle habits or exposure to chemicals. Cancer, for example, may involve tumour-suppressor genes, genes which suppress tumour formation, which lose their function, thus giving rise to carcinomas. Cardiovascular disease tends to manifest itself in specific ways unique to various communities. For example, African communities tend to have strokes as a result of cardiovascular disease, while south asians tend to have heart attacks.

Understanding genetic predisposition to disease and knowledge of lifestyle modifications that either exacerbate the condition or that lessen the potential for diseases (i.e., no smoking or drinking) is necessary for the public to make informed choices. This section on genetic predisposition to disease aims to provide descriptions of major diseases that have a genetic predisposition. It also contains resources for further information from the World Health Organization and other sources.

Cardiovascular Disease


Cancer occurs because of mutations in the genes responsible for cell multiplication and repair. The changes which a cell undergoes in the process of malignant transformation is a reflection of the sequential acquisition of these genetic alterations. This multi-step process is not an abrupt transition from normal to malignant, but may take over 20 years or more. The mutation of critical genes, including supressor genes, oncogenes and genes involved in DNA repair, leads to genetic instability and to progressive loss of differentiation. Tumours enlarge because cancer cells lack the ability to balance cell division by cell death (apoptosis) and by forming their own vascular system (angiogenesis) . The transformed cells lose their ability to interact with each other and exhibit uncontrolled growth, invade neighbouring tissues and eventually spread through the blood stream or the lymphatic system to distant organs.


According to the 2002 World Health Report, about 7.1 million deaths are attributed to cancer each year. The most prevalent of these cancers include lung, stomach, colon, liver, breast and oesophagus cancer, in that order of occurrence. Combined, these cancers are responsible for over 4.2 million deaths. Furthermore, according to the World Cancer Report (IARC 2003) deaths due to cancer will increase by 50% in the next 20 years. Even though generally considered as an illness of the developed countries cancer is a world wide health problem. In 2000 54% of new cancer cases occurred in developing countries. Due to demographic changes and changes in life style this percentage is expected to rise in the near future.

Diagnosis / prognosis:

The roles that genes play differ greatly, ranging from genes that completely determine the disease state ( disease genes) to genes that interact with other genes and environment factors in causing cancer (susceptibility genes).

Studies have shown that the primary determinants of most cancers are lifestyle factors, such as tobacco, dietary and exercise habits, environment carcinogens and infectious agents, rather than inherited genetic factors. In fact, inherited cancer syndromes caused by high penetrance genes transmitted In fact, the proportion of cancers caused by high penetrance genes is low, about less than 5% for breast cancer and less for most other cancer types except retinoblastoma in children.

Inherited mutations of the BRCA 1 gene account for a small proportion of all breast cancers, but affected family members have a greater than 70% lifetime risk for developing breast cancer or ovarian cancer. Identification of a germline mutations by genetic testing allows for preventive measures, clinical management and counselling. Since the prevalence of germline mutations such as BRCA1 is very low in most societies, the introduction of mass screening to identify people at risk to develop cancer is not recommended.

It is now appreciated that so-called metabolic polymorphisms, that is differences in the way people metabolize chemical carcinogens, explain differences in the susceptibility of individuals to cancer, and that these are controlled in cells by mutations in specific genes. A major research endeavour is now under way to characterize these genetic polymorphisms. It is already clear that there are a multiplicity of such genetic changes, that they are caused by genes of low penetrance, and that the classic Mendelian laws do not apply. However, it seems likely that collectively they explain much of innate susceptibility to cancer, and that therefore their potential contribution to the occurrence of cancer is large. It may eventually be possible to identify those individuals at special risk of tobacco or diet-associated cancers, and also those susceptible to the effects of environmental contaminants.

It is also anticipated, but not yet shown, that genetic tests may eventually provide information that will be used to determine the best course of treatment for some cancers. Some cancers currently classified as a single disease may ultimately be classified into different types, each best managed by a different therapeutic strategy.

In conclusion genetics may eventually play an important role in the control of cancer, including:

  • identification of individuals at risk for a specific cancer, leading to preventive or screening strategies for an individual or family members.
  • identification of the subtype of a cancer so that treatment can be tailored to target that specific disease.

Additional resources:


Diabetes is a disease in which the body does not produce or properly use insulin. Insulin is a hormone that is needed to convert sugar, starches and other food into energy needed for daily life. The cause of diabetes continues to be a mystery, although both genetics and environmental factors such as obesity and lack of exercise appear to play roles. There are three major classes of diabetes

Type 1 diabetes

This results from the body's failure to produce insulin, the hormone that "unlocks" the cells of the body, allowing glucose to enter and fuel them.

Type 2 diabetes

This results from insulin resistance which implies that the body fails to properly use insulin, combined with relative insulin deficiency. As a result of this the cells may be starved for energy and over time, high blood glucose levels may damage the eyes, kidneys, nerves or the heart.

Gestational diabetes

This is a type of diabetes, or high blood sugar, that only pregnant women get. If a woman gets high blood sugar when she's pregnant, she has gestational diabetes. It is one of the top health concerns related to pregnancy. If not treated, gestational diabetes can cause problems for mothers and babies.


It is estimated that about 180 million people in the world suffer from diabetes today and more than two-thirds of them live in developing countries. The largest number of persons with diabetes live in India (32 million), China (21 million) and USA (18 million). The vast majority of persons with diabetes have Type 2 diabetes (90-95%). In developed countries about one-third of the persons with diabetes are unaware that they have diabetes, while the proportion of undiagnosed diabetes is even higher in developing countries. This is because classical symptoms of diabetes, like excessive thirst and involuntary weight loss, are often absent in Type 2 diabetes.

Diagnosis / prognosis:

Diabetes is diagnosed by measuring the sugar in the blood. Diabetes is a potentially life-threatening condition if left untreated. If inadequately treated, it can lead to blindness, kidney failure, heart disease and limb amputation. The mainstay of diabetes treatment is diet and regular physical exercise, but the majority of persons with diabetes will need medication as well.

Additional resources:

Cardiovascular disease

Major cardiovascular diseases (CVD) include coronary heart disease, cerebrovascular disease, heart failure, rheumatic heart disease and congenital heart disease. The major risk factors associated with cardiovascular diseases are cigarette smoking, unhealthy diet, physical inactivity, hypertension, diabetes and high blood cholesterol. CVD may also result from a variety of genetic causes, including single-gene mutations, the interaction of multiple genes and environmental factors. Economic transition, urbanisation, industrialization and globalisation bring about lifestyle changes that promote heart disease. Life expectancy in developing countries is rising sharply and people are exposed to these risk factors for longer periods


Heart diseases have no geographical, gender or socioeconomic boundaries. CVD is an important cause of global mortality and in five of the six WHO regions it is the leading causes of mortality. Of the estimated 16.6 million deaths attributed to CVD worldwide, 80% is in developing countries. By 2010, CVD is estimated to be the leading cause of death in developing countries. Patients with established coronary heart disease or cardiovascular disease are at high risk for subsequent coronary and cerebral events Survivors of myocardial infarction are at increased risk of recurrent infarction and have an annual death rate five to six times higher than that of people of the same age who do not have coronary disease.

Diagnosis / prognosis:

Cost effective interventions for prevention and control of the CVD epidemic are available and if effectively implemented have the potential to halve the CVD burden in a short time frame of five years. The mapping of the human genome has contributed to a better understanding of the genetic causal factors associated with CVD. This will allow the development of more precise and effective treatments and management of the CVD in the future.

Additional resources:

Web sites



Asthma is a disease in which the airways become blocked or narrowed. These effects are usually temporary, but they cause shortness of breath, breathing trouble, and other symptoms. When encountering a triggering particle, there is an inflammation of the linings, a constriction of the airways and mucous production. This results in difficulty in breathing, and may even block the airways completely. If an asthma episode is severe, a person may need emergency treatment to restore normal breathing. An asthma episode is triggered by things in the environment. These triggers vary from person to person, but common ones include cold air; exercise; allergens such as dust mites, mould, pollen, Cigarette smoke, animal dander or cockroach debris; and some types of viral infections.

Symptoms of asthma are coughing while exercising or post-exercise, wheezing, shortness of breath, and tightness in the chest.

There are many types of asthma:

  • Exercise-induced
  • Allergy induced
  • Childhood asthma
  • Occupational asthma
  • Chronic asthma

The cause of asthma is not exactly known, but scientists believe that causes may include: genetic heredity, lifestyles, smoking, pollution, and viral infections.


In 2001, 20.3 million people currently had asthma of which 6.3 million were children under age 18 years. Over recent years, the number of people suffering from asthma has increased at an alarming rate. Since the 1980's the incidence of asthma has more than doubled and the American Lung Association believes it will double again by the year 2020.

Diagnosis / prognosis:

Asthma, though it can be a life-threatening condition, can also be managed if asthma patients are keenly observant regarding what triggers their asthma. Identification of the asthma triggers is an important step in living with asthma. Once patients know what triggers their asthma attacks, they can make sure they avoid these triggers in their daily life and be prepared when they know they may encounter them.

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