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Logo of nihpaAbout Author manuscriptsSubmit a manuscriptHHS Public Access; Author Manuscript; Accepted for publication in peer reviewed journal;
Hawaii Med J. Author manuscript; available in PMC 2010 October 13.
Published in final edited form as:
Hawaii Med J. 2009 August; 68(7): 171.
PMCID: PMC2953953

Establishing a Population-Based Cancer Registry DNA Biorepository: The Sharing Ohana Study


As a result of the successful completion of the human genome project [13] there is an opportunity to identify heritable risk factors for cancer on an unprecedented scale. Although there are acknowledged exceptions, such as the genetic identification of women at high risk for breast and ovarian cancers [4], and genetic profiles for prognostic subtypes of breast cancer [5], the specific nature of the heritable risk factors for cancer remains elusive. The characterization of molecular markers for cancer has the potential to improve disease surveillance, treatment optimization, prediction of response to therapy (pharmacogenetics), and drug discovery (pharmacogenomics) [6]. The benefits of such research to individuals and society are likely substantial.

An integral feature of molecular epidemiology as an NCI priority area is the planning and development of strategic partnerships that link epidemiologists with geneticists and other investigators from the clinical, basic and population scientists [7]. Large-scale epidemiological studies will be needed for the full potential of genomic studies to be realized, including individualized cancer prevention based on testing for genetic susceptibilities, the improvement in cancer classification, and the generation of innovative therapies targeted to molecular mechanisms. Population-based clinical and epidemiologic studies are urgently needed to assess the impact of the thousands of genetic variants (and their interactions with modifiable risk factors) on the burden of cancer (incidence, prevalence, as well as morbidity, disability and mortality). A sound population-based epidemiologic approach to genomics is now needed for common complex disorders attributed to gene-environment interactions as a scientific basis for using genetic information in health care and disease prevention [8].

Population-based cancer registries, such as those included in the SEER Program, offer tremendous research potential beyond traditional surveillance activities [9,10]. In 2001, the SEER Program provided supplementation of the Hawaii, Iowa, and Los Angeles County registry contracts to gather tissue from cancer cases within these geographic areas. 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, and assessing therapeutic targets.

The collection of genomic DNA constitutes the next logical step toward increasing the utility of SEER registries. Such collection will allow researchers to measure allele frequencies of cancer-associated genetic polymorphisms or germline mutations in representative samples. Access to DNA 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 specific genetic mutations and tissue profiles. Furthermore, the anonymity of the study subject can be protected through rigorous standards of confidentiality. SEER-based DNA resources represent a step forward in true, population-based DNA repositories from United States’ patients and may serve as a foundation for molecular epidemiology studies of cancer in this country.


The aim of this study is to establish a large SEER-based cohort, recruited from the general population of cancer cases across the State of Hawaii, as a resource for studying the genetics of cancer in areas of current and projected public health importance. DNA and non-identifiable information from this cohort will be made available to researchers locally and nationally. Ultimately, it is intended that this work extend to other population-based cancer registries in the United States. The specific objectives are:

  1. IRB approval. Obtain OMB clearance and local IRB approval to approach cancer cases regarding acquisition of a mouthwash or Oragene specimen to extract genomic DNA.
  2. Recruitment. Recruit and collect interview data and genomic DNA through mouthwash or Oragene kits from all incident cancer cases throughout the State of Hawaii to allow the identification of genetic variants relevant to the etiology and pathogenesis of common and rare cancers.
  3. Public understanding. Characterize the patterns of participation by demographic and clinical characteristics of the patient population to determine resource allocation, and to understand and explain the public reaction to participation in genetic research studies based on a federally- and locally-supported cancer registry.
  4. Research capacity. Create a SEER-wide collaboration that will share knowledge and best practices in population-based cancer registry genetics research.
  5. Health informatics. Create a nationwide research platform in emerging technologies of health informatics in cancer registry-based genetics research.
  6. Exemplar studies. Conduct specific research projects with identified protocols using the resource that will be established.


  1. OMB and IRB approval. A packet will be sent to the OMB and IRB including a sample of the introductory letter, a short questionnaire, a consent form, and instructions on how to use the mouthwash or Oragene kit for specimen collection.
  2. Feasibility study. The feasibility study will include all incident cancer cases diagnosed between January 1, 2008 and June 30, 2008, age 18 or older, who are accessioned by the Hawaii Tumor Registry. [Although ultimately childhood cancer cases might be included, we have decided to limit this feasibility study to adults who can provide consent.] All incident cases will be eligible for inclusion whether or not this is a first or subsequent primary cancer. The introductory letter will include information about the Hawaii Tumor Registry, the Cancer Research Center of Hawaii, the Cancer Information Service, and the rationale for collecting a DNA specimen. A focus group will assist with refining the letter’s contents and message. The initial mailing will include a pilot sample of 200 cases (20 from each of the five main sex-ethnic groups in Hawaii) to determine compliance with the request and to resolve logistical issues. Packets will not be mailed to any case until after a respectful waiting period of at least six weeks following diagnosis. Additional mailings will be batched weekly throughout a six to seven month period with a target of 3,000 cases. Each case will be telephoned approximately 7–10 days after the initial mailing to determine whether the packet was received, to answer any questions that arise, and to enhance compliance with the mouthwash or Oragene collection. All returned questionnaires and mouthwash/Oragene specimens will be processed and stored.
  3. Monetary incentive. We will test the utility of a monetary incentive to obtain a satisfactory response rates during the pilot phase of the study. We will offer a $25 incentive to the first half of the cases mailed a packet during the pilot phase and no compensation to the other half. We will determine whether compensation makes a difference to the cases’ willingness to participate.
  4. Patterns of participation. We will examine patterns of participation by case demographics such as age, sex, race/ethnicity, residence, and socioeconomic status; exposures including tobacco smoking, alcohol drinking, and body mass index; and clinical variables such as cancer site, stage, and multiple primary diagnoses.
  5. Exemplar studies. We will work with local and NCI investigators to examine the distribution of genetic variants, such as the methylenetetrahydrofolate reductase (MTHFR) polymorphism C677T in colon cancer, that have been studied rigorously during the past several years. Allelic distributions will be compared to published data including public databases such as HapMap, dbSNP, SNP500, SeattleSNP and NIEHS.


1. International Human Genome Sequencing Consortium. Initial sequencing and analysis of the human genome. Nature. 2001;409:860–921. [PubMed]
2. Venter JC, Adams MD, Myers EW, et al. The sequence of the human genome. Science. 2001;291:1304–1351. [PubMed]
3. International Human Genome Sequencing Consortium. Finishing the euchromatic sequence of the human genome. Nature. 2004;431:931–945. [PubMed]
4. Nelson HD, Huffman LH, Fu R, Harris EL. Genetic Risk Assessment and BRCA Mutation Testing for Breast and Ovarian Cancer Susceptibility: Systematic Evidence Review for the U.S. Preventive Services Task Force. Ann Intern Med. 2005;143:362–379. [PubMed]
5. Sorlie T, Wang Y, Xiao C, et al. Distinct molecular mechanisms underlying clinically relevant subtypes of breast cancer: gene expression analyses across three different platforms. BMC Genomics. 2006;7:127. [PMC free article] [PubMed]
6. Smith BH, Campbell H, Blackwood D, et al. Generation Scotland: the Scottish Family Health Study; a new resource for researching genes and heritability. BMC Med Genet. 2006;7:74. [PMC free article] [PubMed]
7. Molecular epidemiology: a time for strategic partnerships. NCI Cancer Bulletin. 2004;1(8):1.
8. Khoury MJ, Little J, Burke W. Human genome epidemiology: scope and strategies. In: Khoury MJ, Little J, Burke W, editors. Human Genome epidemiology: A scientific Foundation for Using Genetic Information to Improve Health and Prevent Disease. New York: Oxford University Press; 2004. pp. 3–16.
9. Hernandez BY, Frierson HF, Jr, Moskaluk CA, et al. CK20 and CK7 protein expression in colorectal cancer: demonstration of the utility of a population-based tissue microarray. Human Pathology. 2005;36:275–281. [PubMed]
10. Goodman MT, Hernandez BY, Hewitt S, et al. Tissues from population-based cancer registries: a novel approach to increasing research potential. Human Pathology. 2005;36:812–820. [PubMed]