Tissues from population-based cancer registries: a novel approach to increasing research potential

Summary

Population-based cancer registries, such as those included in the Surveillance, Epidemiology, and End-Results (SEER) Program, offer tremendous research potential beyond traditional surveillance activities. We describe the expansion of SEER registries to gather formalin-fixed, paraffin-embedded tissue from cancer patients on a population basis. Population-based tissue banks have the advantage of providing an unbiased sampling frame for evaluating the public health impact of genes or protein targets that may be used for therapeutic or diagnostic purposes in defined communities. Such repositories provide a unique resource for testing new molecular classification schemes for cancer, validating new biologic markers of malignancy, prognosis and progression, assessing therapeutic targets, and measuring allele frequencies of cancer-associated genetic polymorphisms or germline mutations in representative samples. The assembly of tissue microarrays will allow for the use of rapid, large-scale protein-expression profiling of tumor samples while limiting depletion of this valuable resource. Access to biologic specimens through SEER registries will provide researchers with demographic, clinical, and risk factor information on cancer patients with assured data quality and completeness. Clinical outcome data, such as disease-free survival, can be correlated with previously validated prognostic markers. Furthermore, the anonymity of the study subject can be protected through rigorous standards of confidentiality. SEER-based tissue resources represent a step forward in true, population-based tissue repositories of tumors from US patients and may serve as a foundation for molecular epidemiology studies of cancer in this country.

Introduction

Population-based cancer registries offer a unique potential to generate and test new hypotheses regarding cancer incidence and survival. In the 1960s and 1970s, population-based cancer registries, such as the Hawaii Tumor Registry, were fundamental to epidemiological research comparing cancer rates among various ethnic and racial groups. Migrant studies demonstrated the dominance of environmental (promotional) factors to cancer risk among genetically homogeneous populations [1], [2], [3], [4], [5]. Rates of breast and colon cancers rose dramatically among successive generations of Japanese in the United States, suggesting that changes in diet and other lifestyle behaviors may be important etiologic determinants [5]. These and other observations provided the impetus for the creation of a national program of population-based cancer registries, the Surveillance, Epidemiology, and End-Results (SEER) Program, whose purpose was to assess cancer patterns in the United States.

The SEER Program was an outgrowth of 2 earlier National Cancer Institute (NCI) programs, the National Cancer Survey and the End-Results Program, and was mandated through the National Cancer Act in 1971 [6]. The SEER Program has several goals, chief among which are (1) determining cancer incidence and monitoring cancer trends in selected geographic areas of the United States regarding demographic and social characteristics of the population; (2) estimating cancer incidence for the United States on an annual basis; (3) determining the survival experience for cancer patients and monitoring cancer survival trends with respect to type of cancer, extent of disease, therapy, and demographic, socioeconomic, and other parameters of prognostic importance; (4) identifying cancer risk/protective factors through special studies that disclose groups of the population at high or low risks (these groups may be defined by social, occupational, environmental, dietary, or other characteristics); and (5) identifying factors related to patient survival through special studies of referral patterns, diagnostic procedures, treatment methods, and other aspects of medical care.

The SEER Program presently covers 26% of the United States' population, nearly 74 million people [7]. Use of SEER data have led to a rich history of publications, ranging from ecological and observational studies to cohort and record linkage studies. A list of these publications may be found at the SEER website, http://www.seer.cancer.gov/. The SEER Program is the bedrock of data concerning cancer at the population level in the United States. Other countries have similar programs, but genetic, environmental, and health-care differences pose obstacles to translating findings from these programs to other countries. It is essential that large molecular epidemiology studies be validated in a relevant health-care environment. In this article, we describe an expanded use for SEER and other registries that take advantage of their population basis for cancer tissue collection to support molecular epidemiology (Fig. 1). Population-based tissue banks provide an essential resource for testing new molecular classification schemes of cancer that will augment the pathomorphological approach used presently. Properly annotated SEER-derived tissues will be less influenced by bias associated with tissue collections derived from populations with heterogeneous genetic and environmental backgrounds. As these high throughput assays become cheaper and are applied to larger sets of samples, it is optimal that truly representative collections of tumor tissue are available for testing and validating novel assays. By using new technologies for evaluation of tissue through tissue microarrays (TMAs), it will be possible to assess multiple genetic and protein differences among tumors that can be used for diagnostic and prognostic markers. This information can be rapidly disseminated nationally for the identification and care of cancer patients.