Understanding the Molecular Epidemiology of Tobacco- and Hormone-related Cancers, and Developing Prognostic Gene Signatures to Aid Clinical Management of Head and Neck Cancer Patients

Investigators in the Chen Lab seek to understand the etiology of tobacco-related and hormone-related cancers, and to develop gene expression signatures to predict the clinical outcomes of oral cancer to aid the management of oral cancer patients. Through evaluation of environmental factors, genome-wide data on single nucleotide polymorphisms, heterozygosities, gene copy number alterations, gene expression profiles, and tissue microarray data, we hope to determine the links between environmental and genetic factors and the development of – and/or survival from – tobacco- and hormone-related cancers.

Current studies include:

Oral Cancer: Molecular Profiles and Clinical Outcomes (Oralchip); FFPE Validation of a Prognostic Gene Signature in HPV-Negative Oral Cavity Cancer; Salivary Metabolite Biomarkers for Diagnosing Nodal Metastasis in Oral Cancer

  • What determines which OSCC patients go on to develop local recurrence and/or second primary tumors, so that more aggressive medical treatment and/or surveillance can be offered selectively to these patients?
  • How can we identify those clinically node-negative OSCC patients who harbor occult nodal metastasis, patients who should undergo neck dissection while those without can be spared unnecessary surgery?
  • To what degree can molecular markers improve upon the prediction of survival based on the current staging system so that physicians can better individualize patients’ treatments?

In addition to conducting her own studies on oral cancer, Dr. Chen extends her investigation of the etiology of head and neck cancer through collaboration with other members of the International Head and Neck Cancer Epidemiology Consortium (INHANCE). INHANCE was established in 2004, and hopes to address the following in relation to the occurrence of head and neck cancer: the role of single nucleotide polymorphisms (by conducting genome-wide association studies) and their interactions with environmental factors; the influence of the recency and type of tobacco products and alcoholic beverage consumed; interaction between tobacco and alcohol use; marijuana smoking; sexual behaviors; body mass index; diabetes; and the effects of human papillomavirus (HPV) infection with respect to cancer subsite.

Smoking is a major cause of lung cancer, the most common fatal cancer worldwide. However, most people who smoke do not develop lung cancer. Dr. chen and her team recently completed a study to evaluate if certain people develop lung cancer because of a lower ability to repair DNA damage in their lungs caused by smoking. They also examined how this could be related to other risk factors for lung cancer, such as smoking and a low intake of antioxidant-rich fruits and vegetables. In addition, Dr. Chen has long been collaborating with other members of the International Lung and Cancer Consortium (ILCCO), established in 2004 to share data from case-control and cohort studies so as to evaluate genetic and environmental factors on lung cancer risk and survival. Some of ILCCO’s recent publications in which Dr. Chen participated include a meta-analysis of 14,900 cases and 29,485 controls evaluating the influence of common genetic variation on lung cancer risk, the identification of novel lung cancer susceptibility variants in inflammation pathways, and the discovery of rare variants in BRCA2 and CHEK2 that have a large effect on lung cancer risk.

Endometrial cancer occurs in the inner lining of the uterus. For a number of years, Dr. Chen and her team have been studying the environmental and genetic factors that may influence the development of endometrial cancer. Manuscripts describing the association of potential risk factors, such as diabetes, NSAID use, and long term use of postmenopausal estrogen and progestin have been published. They have also published results describing the associations between endometrial cancer risk and genetic polymorphisms of some of the genes that encode for enzymes that are involved in the biosynthesis or catabolism of estrogens; the response to steroid hormones; and the repair of DNA damages generated during estrogen exposure.

Like oral cancer, endometrial cancer is relatively rare in the U.S. Although its association with exposure to high levels of exogenous unopposed estrogen or endogenous estrogens (as present in obesity) is well known, questions remain regarding the genetic basis for such associations and how might gene-environment interaction influence the risk of this disease. In 2006, several investigators with existing endometrial cancer studies around the country and Dr. Chen established the Epidemiology of Endometrial Cancer Consortium (E2C2) to create an infrastructure for pooled analyses and a collaborative environment to initiate joint investigations into these questions. E2C2 now includes 10 cohort studies and 14 case-control studies. This effort has led to publications on endometrial cancer risk in relation to obesity associated polymorphisms in the FTO and MC4R genes, genome-wide genetic variations (via genome-wide and exome-wide association studies), age at last birth, diabetes and diabetes treatment, and use of intrauterine devices. In addition, we have also reported on the comparisons of risk factors between Black and White women, and between women with Type I and Type II tumors.