Stephen M. Schwartz

The following paragraphs provide summaries of my research interests. More details can be found on my webpage, listed above.

Oral Carcinoma

My studies of the molecular epidemiology of oral squamous cell carcinoma (OSCC) explore the interplay of genetic, virologic, and lifestyle characteristics in both the etiology and prognosis of these cancers. Using data from a population-based case-control study, we have found that the risk of OSCC was related to serologic evidence of both HPV and HSV1 infection, particularly among cigarette smokers. In addition, we found that the detection of HPV DNA in OSCC is related to favorable patient survival. We are currently examining whether OSCC is related to polymorphisms in a variety of genes that are known or suspected of mediating the consequences of tobacco, alcohol, and viral exposures. Examples of genes we have or will study include GSTM1, GSTT1, GSTP1, CYP2E1, NQO1, NAT1, NAT2, EPHX, ADH3, XRCC3, XRCC1, AGT, and XPD. The results should enhance our knowledge of the interaction of environmental and inherited susceptibility to OSCC.

Genital Carcinoma

As part of a Program Project Grant headed by James McDougall, Ph.D., (Cancer Biology Program, FHCRC), I am studying factors related to the prognosis of cervical and other genital cancers. Our goal is to identify tumor markers and other characteristics that in the future may help clinicians predict which patients will develop recurrences and, potentially, target the application of therapies to women at highest risk of relapse. We have found that patients with HPV18-related cervical cancers have reduced survival, and recent immunohistochemical analyses of these tumors suggests that the combination of high cyclin E expression and HPV18 is associated with a particularly poor prognosis.

Uterine Leiomyomata

I have continued my long-standing interest in the etiology of uterine leiomyomata ("fibroids"). Leiomyomata are among the most common neoplasms that develop among women, and although benign, are the leading non-malignant indication for hysterectomy among pre-menopausalwomen. TULEP (The Uterine Leiomyomata Epidemiology Project) is a population-based case-control study we conducted to identify hormonal and hormonally-mediated risk factors for uterine leiomyomata, In addition to an extensive in-person interview focusing on lifestyle, medical, and reproductive characteristics, we collected biologic specimens to determine whether the risk of leiomyomata is related to: (1) urinary excretion of phytoestrogens (lignans, isoflavones); (2) serum organochlorine pesticideand polychlorinated biphenyl residues; and (3) germline polymorphisms in enzymes involved in hormone synthesis and metabolism.

Testicular Carcinoma

I am conducting a population-based case-control study to test the hypothesis that inherited variation in genes involved in stimulating testicular steroidogenesis, synthesizing and metabolizing testosterone, and androgen signaling, is related to the risk of developing testicular germ cell carcinoma (TGCC). In addition to examining gene-gene interactions using the case-control data, we are studying whether blood levels of putative endocrine disrupting chemicals, such as p,p-DDE, pose an increased risk of TGCC among carriers of putative TGCC susceptibility alleles (e.g., large numbers of CAG repeats in the Androgen Receptor gene). We also are employing a case-parent triad design (by recruiting the mothers and fathers of our TGCC cases) to test the hypothesis that maternal carriership of susceptibility alleles in steroid metabolism and growth factor genes are related to TGCC risk.