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Surprising Research

The FOXC2 Gene
(Courtesy of Gentics Home Reference)

The Possible Role of the Insulin Resistance/FOXC2 Gene in Breast Cancer Lymphedema

Information presented here is based on the research report “Breast Cancer Lymphedema: Role of Insulin Resistance/FOXC2” grant presented to Stanley Rockson, MD of Stanford University in 2005. The Final Report, with his surprising findings, was released in 2008.

Hypotheses of the Initial Grant Award (2005)

Since 15-25% of breast cancer survivors develop lymphedema, and this risk does not appear to be strongly linked to the extent of the original disease or surgery, it is likely that hereditary factors play a strong role.

While these factors have not yet been clearly identified, there is a suggestion that a particular gene, whose structure varies in the general population, may be responsible. This gene, known as FOXC2, is of particular interest because it also affects the way in which the body handles sugar, starch, and fat.

When this gene is underactive, the individual is predisposed to resistance to the action of insulin. Insulin resistance has been linked to breast cancer in general, and may be responsible in part, for the risk of lymphedema and for the changes in the lymphedema arm over time.

If we, the researchers, can identify that lymphedema-stricken survivors are more insulin resistant than women without swelling this will provide avenues to treat lymphedema with medication that is currently unavailable.

Also, if the insulin resistance/lymphedema gene is found to vary in the lymphedema patients, it will provide avenues to create screening and prevention strategies in future patients who face breast cancer treatment.

Final Report (2008)

Factors in this study that revealed a predisposition to lymphedema as a complication of breast cancer treatment are not well-defined. However among the systemic factors consistently associated with this lymphedema risk included hypertension (high blood pressure) and obesity (extreme overweight).

Expression of the FOXC2 gene is associated with insulin resistance. It is also implicated in playing a role in lymphatic development.

Therefore, the researchers have postulated that the risk of breast cancer-associated lymphedema may be associated with presence of relative insulin resistance, and that the unifying factor may be relative expression of FOXC2 in the at-risk individuals.

According to Dr. Rockson, “These results of the study to date were unexpected and highly novel.” These results suggest that prevailing elevated levels of circulating insulin may aid in the lymphatic repair response, conferring relative protection against the development of lymphedema.

The researchers propose to pursue these relationships both in animal models of lymphedema and, clinically, in more robust studies of insulin and kinetics in response to glucose challenge. Kinetics is the study of bodies in motion.  

Related Glossary terms

FOXC2 is a gene that provides instructions for making a protein that plays a critical role in the formation of many organs and tissues before birth. Researchers believe that the FOXC2 has a role in a variety of developmental processes, such as the formation of veins, the cardiovascular system, and lymphatic vessels. [1]

Insulin is the hormone produced by the pancreas in response to high glucose (blood sugar) levels. Insulin functions in two ways. [2]

  • First - Insulin allows glucose to enter the cells for use as energy. Glucose, commonly known as blood sugar, is the basic form of energy used by the body.
  • Second - When additional glucose is not needed, insulin stimulates the liver to convert glucose into glycogen for storage. Glycogen is the form in which the liver stores excess glucose.

Insulin resistance A condition in which the body produces insulin but does not use it properly. In an attempt to compensate for this lack of responses, the body secretes more insulin. Insulin resistance increases the chance of developing type 2 diabetes and heart disease.


[1] Content Resource: "Breast Cancer Lymphedema: Role of Insulin Resistance/FOXC2" http://www.cbcrp.org/research/PageGrant.asp?grant_id=4024

[2] Terminology Resource: Medical Terminology for Health Professions, 6th ed by A. Ehrlich and C. Schroeder, Cengage Publishers, 2009, page 388.

© LymphNotes 2014. This information does not replace the advice of a qualified health care professional.

Got a question or comment? Post in the 'Are You at Risk for Lymphedema?' forum.
Category: Are You at Risk for Lymphedema? Updated: 2014-10-29


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