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A PILOT STUDY ESTABLISHES AN ASSOCIATION BETWEEN ESTROGEN LEVELS AND HEAD AND NECK CANCERS

Estrogen, a culprit in breast and gynecologic cancers, may lead to the development of deadly head and neck cancers

NEW ORLEANS -- One of the first studies of its kind has confirmed an association between the development of head and neck cancers and the role of estrogen, known to advance certain types of reproductive cancers. Additional studies planned for the near future will confirm a link between estrogen and head and neck cancers, one of the most deadly of this disease.

Background:

Previous research has confirmed that estrogen promotes cancer in estrogen responsive tissues such as the breast, endometrium, and cervix. Estradiol is the active form of estrogen which is primarily metabolized into two end products, 2-hydroxy estrone (2-OHEI) and 16 -hydroxy estrone (16 -OHE1). The former is inactive and weakly antiestrogenic. Conversely, 16 -OHE1 exhibits full estrogenic activity forming a covalent (or interatomic) bond with estrogen receptors. Increased 16 -OHE1 levels have been associated with a greater risk of reproductive cancers as well as recurrent respiratory papillomatosis of the larynx caused by human papilloma virus.

Essentially, when 2-OHEI levels are low, 16 -OHE1 is high, indicative of patients with cancer. That relationship is increasing severity of laryngeal papillomatosis. This finding caused researchers to believe that head and neck cancer patients would metabolize estrogen differently than matched controls, and these differences would constitute a risk factor in head and neck cancer pathogenesis.

The authors of the study, "Estrogen Metabolism as a Risk Factor for Head and Neck Cancer" are Helen J. Yoo, MD, Stimson P. Schantz, MD, Guo Pei Yu, PhD, and Henedia V. Sirilian, RN, all from the New York Eye and Ear Infirmary, New York, NY; and Daniel W. Sepkovic, PhD and H. Leon Bradlow, PhD, from the Strang Cancer Prevention Laboratory, Cornell Medical College, New York, NY.

The results were presented before the American Academy of Otolaryngology--Head and Neck Surgery Foundation Annual Meeting and Oto Expo being held September 26-29, at the Ernest N. Morial Convention Center in New Orleans, LA. At the gathering, the Academy's 11,000 members will have the opportunity to hear the latest research in the diagnosis and treatment of disorders of the ear, nose, throat, and related structures of the head and neck.

Methodology:

Spot urine samples were collected from 50 patients with cancer and 50 control subjects (without cancer) matched for age and sex (constancy of urine estrogen metabolite ratios over the course years and from 24-hour urine collections has been previously demonstrated). Patients with cancer were recruited from the head and neck clinic at New York Eye and Ear Infirmary who were diagnosed with squamous cell cancer of the upper aerodigestive tract, specifically the oral cavity, pharynx, and larynx. Control patients were from the same clinic with general ear, nose, and throat problems, all with no cancer history. A questionnaire was administered to both groups to determine alcohol, tobacco, and steroid use.

Urine samples were transferred to the Strang Cancer Research Laboratory where levels of estrogen metabolites, 2-hydroxy estrone (2-OHEI) and 16 -hydroxy estrone (16 -OHE1) were determined using an enzyme-linked immunoassay (ELISA). Odds-ration analysis was used to measure the relationship between head and neck cancer risk and urinary estrogen metabolite ratios.

Results:

Key findings of the study were:

* The most common location of cancer was the larynx (60 percent), oropharynx (32 percent) and oral cavity (eight percent). There was no correlation found between low 2 16 /-OHEI ratios and specific disease data such as stage of disease and treatment offered.

* Ninety-four percent of the head and neck cancer patients were tobacco users versus 60 percent of the control group; 59 percent of the cancer patients regularly used alcohol versus 18 percent in the control group.

* Calculated ratios of (2-OHEI)/(16 -OHE1) for each patient defined a pattern of low ratios among the cancer patient group. 15 of 50 cancer patients had low urinary estrogen metabolite ratios compared to two of 50 from the control group.

The results of this study reveal an association between estrogen levels and head and neck cancer and not necessarily a causal relationship. The results call for increased research into this area.

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Editor's Note: For a copy of this study or an interview with Dr. Yoo, contact Ken Satterfield at 703-519-1563 (through 9-21); 9/23-29, call the Annual Meeting Newsroom at 504-670-5409.