Oestrogen may increase the movement of precancerous cells in the mouth and promote the spread of head and neck cancers, reports a US study in Cancer Prevention Research. The results may help researchers to understand the risk factors that cause head and neck cancers in addition to the traditional risk factors of tobacco and alcohol exposure.
Squamous cell carcinoma of the head and neck (HNSCC), which include cancers of the tongue, mouth and throat, represent the sixth most common type of cancer and is known to be on the increase in some demographic groups, including young women without known risk factors. A recent report showed that 75% of young never-smoker/never drinker HNSCC patients who develop primary oral tongue squamous cell carcinoma are women, suggesting that female hormones may contribute to carcinogenesis.
In the current study Margie Clapper and colleagues from Fox Chase Cancer Centre (Philadelphia, Pennsylvania) set out to investigate the impact that oestrogen had on precancerous and cancerous cells. An earlier study by the same group showed that the oestrogen metabolism pathway is altered in lung tissue following tobacco smoke exposure, suggesting that oestrogen metabolism may play a role in the formation of other cancers of the aerodigestive tract.
Using cancer cells grown in the lab, the team found that oestrogen induced the expression of an enzyme called cytochrome P450 1B1 (CYP1B1) which is responsible for breaking down toxins and metabolising oestrogen. The CYP1B1 induction only occurred in precancerous cells and not in healthy cells or cells that had become cancerous.
Furthermore, investigators found that depleting the expression of CYP1B1 reduced the ability of precancerous cells to move and divide, in comparison with similar cells containing normal levels of CYP1B1. Oestrogen also reduced cell death in the precancerous cells, irrespective of the amount of CYP1B1 present.
Finally immunohistochemical staining of samples taken from 128 patients with head and neck cancers showed that 91.9 % stained positive for oestrogen receptor β, 99.4% for CYP1B1 and 88.4% for 17 β oestradiol.
"This study is the first to report the detection of estrogen within human head and neck tissue and demonstrate that both estrogen and CYP1B1 may contribute to the progression of HNSCCs," concluded the authors. They add that CYP1B1 levels may offer an important biomarker of tumorigenesis in head and neck cancers and present a novel target for chemo preventive interventions in patients with premalignant lesions.
Reference
E Shatalova, A Klein-Szanto, K Devarajan et al (2011) Estrogen and Cytochrome P450 1B1 contribute to both early and late-stage head and neck carcinogenesis Cancer Prevention Research Doi:10.1158/1940-6207.CAPR-10-0133