Identification of a mesothelioma phenotype
Tuesday, August 22nd, 2006.
Respiratory Medicine. 2006 Aug 17; [Epub ahead of print] [Link]
Ohar JA, Ampleford EJ, Howard SE, Sterling DA.
Wake Forest University School of Medicine, Section of Pulmonary, Critical Care, Allergy and Immunologic Diseases, Medical Center Boulevard, Winston-Salem, NC 27157-1054, USA.
Abstract
Despite the strong association of asbestos exposure to mesothelioma, only a fraction of persons exposed develop this neoplasm which is characterized by long latency and shortened survival. Familial clustering implicates both exposure and genetic predisposition as causative, but a biologically relevant mesothelioma phenotype essential to genetic analysis has not been defined. To identify a more extensive set of traits that would define a mesothelioma phenotype for the purpose of genetic analysis, we set to determine characteristics that distinguish mesothelioma patients from others exposed to asbestos and to identify factors that predict the presence of mesothelioma over other mesenchymal tumors of the peritoneum and carcinoma metastatic to the pleura. We compared demographics in four asbestos-exposed groups (controls n=347, bronchogenic cancer n=67, mesothelioma n=179 and benign asbestos-induced lung disease (BALD) n=3757). Within the mesothelioma group, we compared traits to identify characteristics associated with shortened survival. We found that compared to other asbestos-exposed groups, subjects with mesothelioma were younger at first asbestos exposure, had a greater risk of a second cancer diagnosis (odds ratio=3.29), had a longer disease latency, and had a greater risk of cancer among first-degree relatives (point estimate for risk 2.93; 95% CI 2.5-3.5). Thoracic tumor location, work exposure and male gender were consistently associated with shortened survival (1.9+/-1.3 years). We conclude that thoracic tumor location, work exposure, male gender, long latency, early age at first exposure, presence of a second cancer, and first-degree relative with cancer define a phenotype that sets mesothelioma patients with a short survival apart from other asbestos-exposed individuals. We propose that this phenotype be applied to candidate gene analysis.
Glossary
- predisposition
- susceptibility to a disease that can be triggered under certain conditions. For example, some women have a family history of breast cancer and are therefore more likely (but not necessarily destined) to develop breast cancer.
- pleura
- (pler-uh) the membrane around the lungs and lining of the chest cavity. (Pleural mesothelioma.)
- neoplasm
- (nee-o-plas-um) an abnormal growth (tumor) that starts from a single altered cell; a neoplasm may be benign or malignant. Cancer is a malignant neoplasm.
- gene
- a segment of DNA that contains information on hereditary characteristics such as hair color, eye color, and height, as well as susceptibility to certain diseases. Women who have BRCA1 or BRCA2 gene mutations (defects) have an inherited tendency to develop breast cancer.
- diagnosis
- identifying a disease by its signs or symptoms, and by using imaging procedures and laboratory findings. The earlier a diagnosis of cancer is made, the better the chance for long-term survival.
- carcinoma
- (car-sin-o-ma) a malignant tumor that begins in the lining layer (epithelial cells) of organs. At least 80% of all cancers are carcinomas.
- cancer
- malignancy; a group of diseases typified by abnormal, generally out-of-control, cell growth.
- benign
- (be-nine) not cancer; not malignant.
- tumor
- an abnormal lump or mass of tissue. Tumors can be benign (not cancerous) or malignant (cancerous).
- mesothelioma
- a tumor derived from mesothelial tissue, such as the peritoneum (lining the abdomen) or pleura (lining the lungs). More on mesothelioma.
