The exact cause of any type of cancer is most likely due to a wide variety of factors. Even though the exact causes for a particular cancer cannon be pinpointed the main risk factors that have been shown to contribute the most to cancer development are personal genetics , and environmental factors. At this point in time the exact causes for myelodysplastic syndrome, like almost all other forms of cancer, are not precisely known. The exact causes for myelodysplastic syndrome are not know because of the fact that the formation of tumors is a multi-step process that requires that acquisition of a wide range of different DNA mutations, which randomly occur in response to a multitude of different internal and external agents. In the case of myelodysplasia, there are marked contributors to all three, with some being more pronounced than others.

Even though the exact causes of myelodysplastic syndrome are not known, several risk factors associated with myelodysplastic syndrome have been identified. A risk factor is any variable that has been proven to be associated with an increased risk of contracting a disease. Some of the possible personal risk factors that have been associated with myelodysplastic syndrome have to do with the sex, age, as well as the health of the person. Studies have shown that males have a higher likelihood of contracting myelodysplastic syndrome, as there have been shown to be more documented cases of MDS in males then in females.

It has also become evident that the older the patient is the higher the likelihood is of that person acquiring MDS, as there have been very few recorded cases of MDS in patients that are younger than 40 years old and there is a significant increases in the number of cases of MDS in patients that are older than 60 years of age.

Evidence also suggests that previously having cancer and being treated with certain cancer treating drugs is also a risk factor to myelodysplastic syndrome. Studies have shown that exposure to certain cancer treating drugs can lead to an increase in the likelihood of contracting myelodysplastic syndrome. Exposure to the cancer treating drugs: Mechlorethamine, Procarbazine, Chlorambucil, Etoposide, teniposide, Cyclophosphamide, ifosfamide, and Doxorubicin, along with a few others have been shown to lead to an increase likelihood of contracting MDS.

Research also suggests that tobacco smoke is also a risk factor of myelodysplastic syndrome. Tobacco smoke has also been shown to lead to an increase in the chance of developing MDS, as well as a variety of other mouth and throat cancers, as substances within the tobacco plant have been proven to be mutagenic agents.

Although all of the genetic mutations associated with myelodysplastic syndrome have yet to be determined a few genetic risk factors for myelodysplastic syndrome have been determined. The most important genetic risk factor associated with MDS appears to be the hypomethylation of the individuals DNA. Proper methylation of the DNA ensures DNA stability and proper gene expression among numerous other functions. The DNA of some of the patients who have MDS has been shown to be hyopmethylated. A study published in conjunction with the American Society of Clinical Oncology has shown that 5-Aza-2-deoxycytidine, a DNA hypomethylating agent, has a 50% response rate in a small phase II study in elderly patients with high-risk myelodysplastic syndrome. Another genetic risk factor seems to be the acquisition of mutant genes that are associated with Fanconi anemia, Shwachman-Diamond syndrome, familial platelet disorder, and severe congenital neutropenia. If the individual happened to have been passes down mutant genes that have been found to be associated with the previously stated disorders the person has a higher chance of acquiring MDS. It has long been proven that that loss of the long arm of chromosome 5 has been associated with the dysplastic abnormalities of hematopoietic stem cells. Luckily in 2005 the FDA approved the drug Lenalidomide as a treatment for MDS patients who suffered from the loss of the long arm of chromosome 5. Recently a mutation in the U2AF1 gene has also been associated with myelodysplastic syndrome have also been identified. A study published in The Lacent, the world's leading general medical journal has also shown that individuals with the deletion of the GSTT1 gene may have a higher susceptibility to MDS then the individuals who do not have that gene deleted. The mechanism implicated by the study might involve a decreased detoxification of environmental or endogenous carcinogens.

The etiology of myelodysplastic syndrome (MDS) isn’t well known. However, there have been multiple studies done into the matter that have shown cursory links between environmental and occupational factors that can increase a man’s risk of developing myelodysplasia. One of the biggest environment factors that increase a man’s chance is his occupation.

Several occupations have an increased risk of MDS. Farmers have one of the more well studied occupational risks that expose him to compounds that that can promote MDS. Chemical exposures, such as diesel, petrol pesticides, or fertilizers, have been linked to MDS. Farmers are in constant contact with these compounds in the use of farm equipment and the maintenance of their fields. Technical or factory workers, such as machine operators, textile workers are also at risk. These works are exposed to oils and solvents, dust from the machines, as well as risk of infection. Other occupations that increase a man’s risk are aeromechanics, carpenter and welders, electricians, as well as truck drivers. The main points of occupational risk factors are the compounds to which they are exposed. All the occupations listed are exposed to petroleum products, as well as industrial lubes and solvents.

Smoking has a weak relationship to someone developing myelodysplasia. While smoking is a known in causing many cancers, its link to MDS is still cursory. Studies on smoking role in MDS show contradictory and inconclusive results. However, there is a sense of logical in a correlation relationship. Cigarette smoke has benzene in it and smokers have higher levels of benzene in their blood. Benzene has been shown to be a risk for MDS.

Even though several risk factors associated with myelodysplastic syndrome have been identified it is impossible to say what the particular reason for contracting MDS is. Cancer is a complex process that often takes years and there is not a lone factor that causes the cancer. Coming in contact with the risk factors stated above does not necessarily mean that an individual will contract a type of cancer, and staying away from these risk factors does not ensure one will not contract cancer as everyone is different and everyone body reacts differently to the various external and internal mutagenic agents.