The Division has recently been awarded several significant NIH/NCI awards in cancer genetics that integrate the leadership and talent of its faculty. The "UCI-UCSD Cancer Genetics Network Center" (NCI, Anton-Culver) establishes UCI as one of eight new interdisciplinary Cancer Genetics Networks that will provide the infrastructure for research investigations of the genetic basis of human cancer susceptibility and identify means to address the public health issues associated with human cancer genetics.

The "Hereditary Breast Cancer: Genetic and Molecular Studies" (NCI, Anton-Culver) has also been renewed for an additional five years. The competitive renewal application will maintain and follow-up the existing family resource of 1270 breast and 262 ovarian cancer probands, further characterize BRCA mutations in breast and ovarian cancer families and explore the associated functions of BRCA1 missense mutations. In addition, the investigators will determine whether there is molecular genetic evidence for the aggregation of breast and colorectal cancer in a subgroup of the existing high-risk breast cancer families. There is strong familial and molecular genetic evidence of an association between breast and ovarian cancer and also a familial association between breast and colon cancer. Further, preliminary results show mutations in MSH2 and MLH1 in breast cancer families where there is colon cancer in first or second degree relatives. The candidate genes (such as mismatch repair genes) relevant to the tumor spectrum in these families in addition to BRCA1 and BRCA2 will be examined and possible new genetic alterations will be explored. The data generated from the proposed study will have yield novel and important information to the scientific and clinical community as well as for subjects from breast cancer families possessing the diverse spectrum of tumors as is often observed in familial breast cancer.

The "Breast and Other Cancers in the California Teacher's Cohort" (NCI, Wright/Anton-Culver) has also received recent approval. A cohort of 133,000 California schoolteachers had been established by a collaborative group of epidemiological investigators with the goal of evaluating unresolved issues related to breast cancer risk factors. UCI investigators Anton-Culver, Ziogas, Peel and Lin will assess modification of breast cancer risk by other risk factors in women with and without a family history of breast and other cancers. They will conduct a validation study of self-reported family history of cancer, by cancer type and by family relationships of affected individuals. A major focus will be breast and ovarian cancer, but long-range goals of the CTS cohort will include familial and genetic studies of other cancers including malignant melanoma, endometrial cancer, and colorectal cancer. Therefore, the investigators will: a) evaluate the validity of family history data collected from self-reports by the cancer type and family relationship (degree of closeness to the proband) in a sample of the CTS cohort who reported in the baseline questionnaire a positive family history of breast cancer in at least one first-degree relative. Comparisons will be made between data provided by the baseline questionnaire and details from in-person interviews, medical records, and death certificates.

The goal of "Breast Cancer Radiation Exposure and ATM Expression" (NCI, Bernstein/Anton-Culver) is to establish a population-based cohort of bilateral breast cancer cases diagnosed since 1984 with a four-year lag between primaries and unilateral breast cancer controls to investigate breast cancer radiation exposure and ATM expression.

The "Chemoprevention of Familial Prostate Cancer" (NCI, Meyskens/Anton-Culver) is a program project grant. The aims of Project 1 are to: 1) develop a population-based series of families with 2 or more first degree relatives with prostate cancer; 2) characterize alterations on chromosome 1q in prostate cancer; 3) assess whether expression of susceptibility genes (or presence of other genetic alterations) may be modified by environmental factors; and, 4) provide a well-characterized cohort of brothers or male cousins for the chemoprevention trial (Project III) and surrogate endpoint biomarker studies (Project II).

In "Genetic Susceptibility to Melanoma: A Model for Gene-Gene and Gene-Environment Interaction" (NCI, Berwick/Anton-Culver), the major goals of this project are to 1) determine the relative risk for developing melanoma due to germline mutations and polymorphisms in the cell cycle genes, CDKN2A and CDK4, 2) determine the relative risk for developing melanoma due to polymorphisms in the melanocortin receptor gene MC1R, a major pigmentary gene, 3) determine the relative risk for developing melanoma due to allelic variation in the DNA repair genes that specialize in removing DNA damage due to UV radiation, the nucleotide excision repair genes (NER), and 4) analyze the interactions among genetic variants that are associated with the development of melanoma and their association with solar UV radiation.

An innovative cancer control program that could revolutionize the approach to cervix cancer prevention, "Single-Visit Cervical Cancer Prevention Program" (NCI, Manetta), has recently been launched by Community Research investigators. A significant barrier to the diagnosis and management of cervical cancer is the loss to follow-up for those who undergo screening using the Pap smear. In addition, other barriers include lack of education, cultural-based attitudes and health behaviors, as well as, socioeconomic factors. The usual approach to cervix cancer screening diagnosis and management is seen as accentuating these problems due to loss to follow-up and these barriers. This intervention study will determine the effectiveness of a single-visit program (SVP), including the diagnosis and treatment of patients with pre-malignant conditions, in decreasing the rate of loss to follow-up of women with abnormal Pap smears.

The Division has also recently been awarded a significant NIH/NHLBI award as a Field Center for a study entitled "Iron Overload & Hereditary Hemochromatosis" (NHLBI, McLaren). The Center will screen 20,000 primary care patients for iron overload and hereditary hemochromatosis at the ambulatory care clinics at UCI and UCLA. The primary goal of the Field Center is to contribute to the epidemiologic study of iron overload and hereditary hemochromatosis, in a multi-center, multiethnic, primary care-based sample. Major areas to be addressed include prevalence estimation, disease screening, mixture distribution analysis, and sequential analysis of laboratory data.

Asthma research includes "Asthma and Exposure to Peaks in Particulate Air Pollution" (NIEHS, Delfino) to assess whether peak hourly exposures to particular matter of outdoor origin will be more closely associated with acute asthmatic responses to particles than 24-hour average exposures in susceptible individuals, and, whether personal hourly exposure to particulate matter from micro-environmental models, and particle dose to target zones in the respiratory tract, will be more closely associated with daily asthma severity than unadjusted outdoor particle concentrations. Another asthma study, "Evaluation of the Health Effects of Toxic Air Pollutants in a Southern California Community: A Pilot Study" (California Air Resources Board, Delfino) will: examine the relationship of the daily incidence and severity of asthma to concentrations of air pollutants, controlling for criteria air pollutants, temporal factors, weather and respiratory infections reported in diaries; examine the relationship of the daily incidence and severity of migraine to concentrations of air pollutants controlling for criteria air pollutants, temporal factors, weather and other putative causes reported in diaries; field test patient diaries for the evaluation of acute episodes of symptoms over a two week period in a subset of subjects; and to estimate the statistical associations between simultaneously measured concentrations of 224 breath sample VOCs and ambient air pollutants from a representative outdoor stationary site in a selected area.

Quality of life research includes "Quality of Life of Gynecologic Cancer Survivors" (NCI, Wenzel) to investigate and refine a gynecologic malignancy survivorship model through evaluation of quality of life concerns and survivorship sequelae of women who are long-term early stage ovarian and endometrial cancer survivors and to examine potential QOL differences for endometrial cancer clinical trial survivors.

The Biostatistics Shared Resource (BSR) of the UCI Chao Family Comprehensive Cancer Center is directed by Dr. Christine McLaren. The BSR provides biostatistical support for all members of the Cancer Center in both study design and study analyses.

Dr. McLaren’s statistical modeling research provides insight into the structure of data where models of biological processes can assist with distinguishing between health and disease. Her research has concentrated on mixture distribution analysis, goodness-of-fit testing, and hierarchical regression modeling of longitudinal data. Medical applications including disease prevalence and estimation of iron overload and hemochromatosis, analysis of distributions of red blood cell volume and hemoglobin concentration in iron deficiency anemia, detection of cisplatin-induced anemia in patients undergoing cancer chemotherapy, and screening for hepatocelluar carcinoma. As a result of her experience with statistical modeling and collaborative medical research, in January of 2000, Dr. McLaren received a $4 million 5-year contract awarded by NIH/NHLBI, "Screening for Iron Overload and Hereditary Hemochromatosis—Field Center," described above.

A pilot study funded by a Cancer Center cancer control initiative entitled "Ascertainment Bias in Family Studies" seeks to present general statistical frameworks for analyzing family-based case-control data. In particular, breast cancer incidence models are derived conditional on ascertainment that allow for censored data as well as time dependent covariates, and a likelihood-based approach of partial segregation that utilizes all available information on phenotypes of probands and their relatives. A comparison between the two approaches in terms of relative efficiency, bias, and ascertainment will be investigated.

As part of the program project grant described above, "Chemoprevention of Familial Prostate Cancer" (NCI, Meyskens/Anton-Culver), a biostatistical core will provide biostatistical support for Projects I, II and III.

They will conduct a validation study of self-reported family history of cancer, by cancer type and by family relationships of affected individuals. A major focus will be breast and ovarian cancer, but long-range goals of the CTS cohort will include familial and genetic studies of other cancers including malignant melanoma, endometrial cancer, and colorectal cancer. Therefore, the investigators will: a) evaluate the validity of family history data collected from self-reports by the cancer type and family relationship (degree of closeness to the proband) in a sample of the CTS cohort who reported in the baseline questionnaire a positive family history of breast cancer in at least one first-degree relative. Comparisons will be made between data provided by the baseline questionnaire genetics information and resources within the larger cancer genetics community.

The Cancer Surveillance Program of Orange County (CSPOC), Region 10, and the San Diego/Imperial Organization for Cancer Control (SANDIOCC), Region 7, were developed as population-based regional cancer registries as part of the statewide cancer reporting system, the California Cancer Registry (CCR). The CCR is a component of the Cancer Surveillance Section (CSS) of the California Department of Health Services (CDHS). The CCR is also a collaborative effort between the State and the California Public Health Foundation (CPHF). Under the mandate of the Statewide Cancer Reporting Law (Sections 103875, 103885 and 100330 of the California Health and Safety Code), CSPOC/SANDIOCC has been conducting cancer surveillance since 1988 under Subcontract 050-8710/8707 with the California Public Health Foundation. Its cancer reporting capabilities are enhanced by funding from the Centers for Disease Control and Prevention Subcontract 455B-8703-S3505 to improve timeliness, improve quality, expand data collected, expand data utilization, and to support and enhance the regional registries operations and its potential for use in research.

The goals of the Cancer Surveillance Program of Orange County/San Diego Imperial Organization for Cancer Control are to:

• conduct surveillance of cancer, a reportable disease under legislative mandate (California Health and Safety Code 210, 211.3, and 211.5) since 1983
• require all California physicians, hospitals, pathology laboratories, and coroner's offices to report all cancer diagnoses and follow-up to their respective regional cancer registries
• provide a focus for scientists, clinicians, and members of the healthcare community to promote cancer prevention and control
• conduct cancer surveillance of the 6.5 million residents of Orange, San Diego, and Imperial Counties

The Surveillance, Epidemiology and End Results (SEER) expansion program is to collaborate with the Public Health Institute. This project is closely related to program such as the Cancer Surveillance Program of Orange County/San Diego Imperial Organization for Cancer Control (CSPOC) and Support and Enhancement of the Existing Cancer Registry in California, a subcontract to UCI from Public Health Institute under a Centers for Disease Control program.

The SEER program assembles data on cancer incidence and deaths in the United States and monitors trends in incident rates to look for unusual changes in certain cancers and also searches for such demographic connection with cancer as ethnicity, gender, age and geography. The SEER collects data from at least a dozen cancer registries nation wide. It has recently expanded to include UCI’s statistics and those of Louisiana, Kentucky and New Jersey. With its expansion, the SEER program covers data from about 26 percent of the nations population, up from 14 percent before the expansion. State cancer registries are set up by government public health agencies to account for every case of cancer diagnosed in a certain region. The registries then contribute to their data to SEER as well as other cancer databases. The UCI researchers will manage and contribute data on cancer incidence as reported from California hospitals, pathology labs and physicians’ offices. As part of SEER the group will be responsible for reporting registry data, ensuring that registry reporting is complete, conducting follow-up studies on living cancer patients and editing cancer data to make sure its accurate.

The goals of the SEER program are to:

· Perform semi-annual casefinding at pathology laboratories to increase timeliness of reporting.

· Increase visual editing and consolidation efforts to meet completeness of reporting requirement.

· Perform active follow-up for live patients diagnosed from 1988 forward.

· Perform case finding audits to ensure complete and accurate data.

· Perform visual editing of treatment data to ensure accuracy of abstracting and coding.