Family history of haematopoietic malignancies and non-Hodgkin's lymphoma risk in the California Teachers Study.

Family history of haematopoietic malignancies appears to be a risk factor for non-Hodgkin's lymphoma (NHL), but whether risk varies by family member's gender is unclear. Among 121 216 women participating in the prospective California Teachers Study, NHL risk varied by type of haematopoietic malignancy and gender of the relative.

Validating genetic risk associations for ovarian cancer through the international Ovarian Cancer Association Consortium.

The search for genetic variants associated with ovarian cancer risk has focused on pathways including sex steroid hormones, DNA repair, and cell cycle control. The Ovarian Cancer Association Consortium (OCAC) identified 10 single-nucleotide polymorphisms (SNPs) in genes in these pathways, which had been genotyped by Consortium members and a pooled analysis of these data was conducted. Three of the 10 SNPs showed evidence of an association with ovarian cancer at P< or =0.10 in a log-additive model: rs2740574 in CYP3A4 (P=0.011), rs1805386 in LIG4 (P=0.007), and rs3218536 in XRCC2 (P=0.095). Additional genotyping in other OCAC studies was undertaken and only the variant in CYP3A4, rs2740574, continued to show an association in the replication data among homozygous carriers: OR(homozygous(hom))=2.50 (95% CI 0.54-11.57, P=0.24) with 1406 cases and 2827 controls. Overall, in the combined data the odds ratio was 2.81 among carriers of two copies of the minor allele (95% CI 1.20-6.56, P=0.017, p(het) across studies=0.42) with 1969 cases and 3491 controls. There was no association among heterozygous carriers. CYP3A4 encodes a key enzyme in oestrogen metabolism and our finding between rs2740574 and risk of ovarian cancer suggests that this pathway may be involved in ovarian carcinogenesis. Additional follow-up is warranted.

The BOADICEA model of genetic susceptibility to breast and ovarian cancers: updates and extensions.

Multiple genetic loci confer susceptibility to breast and ovarian cancers. We have previously developed a model (BOADICEA) under which susceptibility to breast cancer is explained by mutations in BRCA1 and BRCA2, as well as by the joint multiplicative effects of many genes (polygenic component). We have now updated BOADICEA using additional family data from two UK population-based studies of breast cancer and family data from BRCA1 and BRCA2 carriers identified by 22 population-based studies of breast or ovarian cancer. The combined data set includes 2785 families (301 BRCA1 positive and 236 BRCA2 positive). Incidences were smoothed using locally weighted regression techniques to avoid large variations between adjacent intervals. A birth cohort effect on the cancer risks was implemented, whereby each individual was assumed to develop cancer according to calendar period-specific incidences. The fitted model predicts that the average breast cancer risks in carriers increase in more recent birth cohorts. For example, the average cumulative breast cancer risk to age 70 years among BRCA1 carriers is 50% for women born in 1920-1929 and 58% among women born after 1950. The model was further extended to take into account the risks of male breast, prostate and pancreatic cancer, and to allow for the risk of multiple cancers. BOADICEA can be used to predict carrier probabilities and cancer risks to individuals with any family history, and has been implemented in a user-friendly Web-based program (http://www.srl.cam.ac.uk/genepi/boadicea/boadicea_home.html).

Hypertension, diuretics and breast cancer risk.

It is unclear whether hypertension and antihypertensive medication use are associated with breast cancer. In order to examine these associations, we conducted a case-control study among women aged 50-75 years. Breast cancer cases were ascertained via a population-based cancer registry (n=523) and controls were ascertained via random-digit-dialing (n=131). Participants completed a self-administered questionnaire which queried history of hypertension, antihypertensive medication use and risk factors. Unconditional logistic regression was used to estimate the odds ratio (OR) and 95% confidence intervals (CI), adjusted for age, body mass index (BMI), diabetes, smoking, alcohol use, menopausal status, family history of breast or ovarian cancer, age at first full-term pregnancy and education. History of treated hypertension was associated with significant increased risk of breast cancer (OR, 1.77; 95% CI, 1.04-3.03) and this association appeared only in women with BMI > or =25 kg/m(2) (OR, 2.30; 95% CI, 1.12-4.71). Diuretic use was also associated with elevated breast cancer risk (OR, 1.79; 95% CI, 1.07-3.01). The risk associated with diuretic use increased with duration of use (P for trend, <0.01). Use of other blood pressure medications was not found to be associated with breast cancer risk. These results support a positive association between treated hypertension, diuretic use and breast cancer risk among women aged 50-75 years.

Breast and ovarian cancer risks to carriers of the BRCA1 5382insC and 185delAG and BRCA2 6174delT mutations: a combined analysis of 22 population based studies.

A recent report estimated the breast cancer risks in carriers of the three Ashkenazi founder mutations to be higher than previously published estimates derived from population based studies. In an attempt to confirm this, the breast and ovarian cancer risks associated with the three Ashkenazi founder mutations were estimated using families included in a previous meta-analysis of populatrion based studies. The estimated breast cancer risks for each of the founder BRCA1 and BRCA2 mutations were similar to the corresponding estimates based on all BRCA1 or BRCA2 mutations in the meta-analysis. These estimates appear to be consistent with the observed prevalence of the mutations in the Ashkenazi Jewish population.

Characterization of hereditary nonpolyposis colorectal cancer families from a population-based series of cases.

BACKGROUND: The incidence of hereditary nonpolyposis colon cancer (HNPCC) in the general population is not well defined because of the lack of large population-based studies. We characterized the incidence of HNPCC in a large, population-based cohort of colorectal cancer probands and analyzed the location of colorectal tumors. METHODS: Of the participating 1134 probands from three counties in Southern California, 907 had a negative family history of colorectal cancer and 227 had a positive family history of colorectal cancer. In addition, 11 referral case subjects with HNPCC were used to study mutation frequencies in two mismatch repair genes (MSH2 and MLH1) and microsatellite instability. All statistical tests were two-sided. RESULTS: Among the probands diagnosed in Orange County during 1994 (population-based sample, all ages), five were consistent with the Amsterdam criteria for HNPCC (0.9%; 95% confidence interval [CI] = 0. 3%-2.1%). Among probands diagnosed at less than 65 years of age-from the wider three-county area and a longer time span-16 (2.1%; 95% CI = 1.2%-3.4%) had a clinical history consistent with the Amsterdam criteria for HNPCC. Five (approximately 45%) of 11 of the referral HNPCC case subjects had a mutation in MSH2 or MLH1 and also showed microsatellite instability. The family members of case subjects with mutations tended to show an earlier age at diagnosis of HNPCC and more multiple primary cancers than those of case subjects without detectable mutations. Many of the known characteristics of HNPCC, including the presence of ureteral and endometrial cancers, were seen in both sets of families. The previously reported proximal location of colorectal tumors in HNPCC kindreds was not seen in the population-based dataset but was similar to the location reported in the referral cases. CONCLUSIONS: On the basis of our data, we believe that the prevalence of HNPCC in the general population is likely to be closer to 1% than to 5%. Furthermore, our study suggests that some previously reported characteristics of HNPCC, such as the proximal location of tumors in the syndrome, may not always hold true in a population-based sample.

Human papillomavirus type 18: association with poor prognosis in early stage cervical cancer.

BACKGROUND: Cervical carcinoma is a leading cause of mortality from cancer among women worldwide, accounting for approximately 160,000 deaths annually. Prognosis in patients with this disease is dependent on several well-established clinical features (stage of disease and age of patient) and pathologic features (lymph node status, grade of tumor, and depth of invasion). Although the features associated with poor clinical outcome have been well studied, molecular markers such as human papillomavirus (HPV) type that may reflect the underlying biologic basis for clinical behavior are poorly understood. PURPOSE: To test the hypothesis that differences in survival among patients with cervical carcinoma are associated with HPV DNA type, we conducted a historical cohort study of patients treated at our institutions over a 10-year period. METHODS: Fresh primary tumor tissue samples from 291 women with all stages of cervical carcinoma diagnosed from April 1983 through August 1993 were rapidly frozen and stored at -70 degrees C until analysis. High-molecular-weight DNA was extracted and purified by homogenization, proteinase K digestion, phenol extraction, ammonium acetate salt displacement, ethanol precipitation, and ribonuclease treatment. HPV nucleotide sequences were amplified from tumor DNA samples by polymerase chain reaction with the use of both consensus L1 (MY09/MY11) primers that recognize more than 25 HPV types and modifications of type-specific primers developed for HPV types 16, 18, and 6. Clinical data were abstracted from hospital, office, and tumor registry records. Univariate analysis was conducted using Student's t test and chi-squared tests. Survival curves were estimated by use of the Kaplan-Meier method; differences between groups were examined by the logrank test. Multivariate survival analysis was performed according to the Cox proportional hazards model. RESULTS: HPV DNA was detected in 247 (85%) of 291 tumors: HPV16 in 52%, HPV18 in 20%, other HPV types in 13%, and no HPV DNA in 15%. Eighty-eight percent of squamous tumors contained HPV DNA compared with 79% of adenocarcinomas, the latter harboring predominantly HPV18. Women 45 years old or younger with a history of cigarette smoking tended to have HPV DNA in their tumors, but the HPV type was not associated with established prognostic factors such as stage, grade, lymph node metastasis, or depth of stromal invasion. After a median follow-up of 38.9 months, among potential prognostic factors of patient age, histologic cell type, grade, and HPV DNA status, only stage was predictive of survival in the entire study population. However, among the 171 patients treated with type III radical hysterectomy (removal of uterus and upper vagina along with other tissues extending to the pelvic wall) and pelvic lymphadenectomy (removal of all lymphatic tissue in the pelvis), multivariate analysis determined that lymph node status (adjusted risk ratio [RR] = 3.12; 95% confidence interval [CI] = 1.35-7.21), depth of stromal invasion (adjusted RR = 3.14; 95% Cl = 1.05-9.34), and the presence of HPV18 DNA (adjusted RR = 2.59; 95% CI = 1.08-6.22) were statistically significant predictors of survival. CONCLUSION: HPV18 DNA type is an independent prognostic factor in patients with cervical carcinomas treated with radical hysterectomy and pelvic lymphadenectomy. IMPLICATIONS: The use of molecular markers such as HPV DNA type may allow the identification of patients with early stage cervical cancer at high risk for disease recurrence.

Incidence of lung cancer by histological type from a population-based registry.

Using data from a population-based registry, the Cancer Surveillance Program of Orange County, we examined patterns in lung cancer incidence by histological type for 1984 in Orange County, CA. Age-adjusted incidence rates per 100,000 population are 66.4 for men and 34.1 for women. Compared to 1983 rates for whites from all SEER areas combined, Orange County incidence rates are lower for men but equal for women. Squamous cell carcinoma incidence shows a strong male predominance [male/female 3.4; 95% confidence interval = (2.6, 4.4)], whereas the male/female incidence ratios for adenocarcinoma [male/female 1.4; 95% confidence interval = (1.1, 1.8)] and small cell carcinoma [male/female = 1.8; 95% confidence interval = 1.3, 2.4)] are closer to unity. Smoking habits were abstracted from medical records for 79% of cases. Only 8% of lung cancer cases (5% of men and 12% of women) with known smoking habits are nonsmokers. Adenocarcinoma is the most common cell type among women smokers and nonsmokers, while squamous cell carcinoma predominates in both male smokers and nonsmokers. Cases who smoked were younger at diagnosis than nonsmokers (P less than 0.001) for each cell type. Despite a greater proportion of nonsmokers, cases with adenocarcinoma were younger at diagnosis compared to small cell carcinoma (P less than 0.01) and squamous cell carcinoma (P less than 0.05). The observed patterns of incidence rates by histological type are not entirely explained by current knowledge of the relationship between smoking and cell type.

Germ-line msh6 mutations in colorectal cancer families.

Hereditary nonpolyposis colorectal carcinoma (HNPCC) is due primarily to inherited mutations in two mismatch repair genes, MSH2 and MLH1, whereas germ-line mutations in other mismatch repair genes are rare. We examined the frequency of germ-line msh6 mutations in a population-based series of 140 colorectal cancer patients, including 45 sporadic cases, 91 familial non-HNPCC cases, and 4 HNPCC cases. Among the 91 population-based familial non-HNPCC cases, germ-line msh6 mutations were found in 6 patients (7.1% of probands analyzed; median age at diagnosis, 61 years). These mutations included a splice site mutation, a frameshift mutation, two missense mutations that were demonstrated to be loss of function mutations, and two missense mutations for which functional studies were not possible. In contrast, germ-line msh6 mutations were not found in any of the 45 sporadic cases and the 4 HNPCC cases in the population-based series or in the second series of 58 clinic-based, primarily HNPCC families. Our data suggest that germ-line msh6 mutations predispose individuals to primarily late-onset, familial colorectal carcinomas that do not fulfill classic criteria for HNPCC.

A germline 2.35 kb deletion of p53 genomic DNA creating a specific loss of the oligomerization domain inherited in a Li-Fraumeni syndrome family.

The primary genetic cancer predisposing event in many Li-Fraumeni syndrome families is a germline mutation in the p53 gene. We describe an extended Li-Fraumeni family with a germline mutation in the p53 gene involving a deletion of exon 10. The mutation is a 2.35 kilobase intragenic deletion encompassing exon 10, which results in the specific loss of the entire p53 oligomerization domain. This mutation segregates with the cancer phenotype. A lymphoblastoid cell line developed from a mutation carrier shows accumulation of mutant p53 protein by immunoblotting. However, tumor tissues from two affected carriers are negative by immunohistochemical staining. A major structural alteration specifically involving the oligomerization domain of a germline p53 gene has not been previously described and occurs in a region rarely mutated in sporadic tumors. The oligomerization domain is dispensable for many wild-type p53 functions, including transactivation, sequence-specific DNA binding, and suppression of oncogenic transformation. However, the domain appears to be required for transcriptional repression, and DNA strand reassociation. The identification of this mutation in an LFS family may yield insights into the importance of the oligomerization domain for suppressor function of the p53 tumor suppressor gene.

Breast cancer, passive and active cigarette smoking and N-acetyltransferase 2 genotype.

The relationship of breast cancer to cigarette smoking is inconsistent in the literature, possibly due in part to heterogeneity in carcinogen metabolism. N-acetyltransferase 2 (NAT2) enzyme activity is believed to play a role in the activation of tobacco smoke carcinogens. We examined the effect of NAT2 genetic polymorphisms on risk of breast cancer from active and passive smoking. Women were recruited from those who had suspicious breast masses detected clinically and/or mammographically. Questionnaire data were collected prior to biopsy diagnosis to blind subjects and interviewers. Histopathology showed 113 cases with mammary carcinoma (30 carcinoma in situ) and 278 controls with benign breast disease. NAT2 genotype was determined using allele-specific polymerase chain reaction amplification to detect slow acetylator mutations. Effects of passive and active tobacco smoke and of NAT2 genotype on breast cancer risk were examined with logistic regression controlling for known risk factors. Models first included all controls, and subsequently 107 with no or low risk (normal breast or no hyperplasia), and finally 148 with high risk (hyperplasia, atypical hyperplasia, complex fibroadenomas). Referents had no active or passive smoke exposure. We found no association between breast cancer risk and NAT2, smoking status (never, former, current), smoking duration, or cigarettes per day. There were no effects of passive exposure among never-smokers. Models were unchanged across control groups. There were no statistical interactions between tobacco smoke exposure and NAT2. The results were similar when restricting the analysis to invasive cancers. These findings do not support the hypothesis that NAT2 is a risk factor for breast cancer or that it alters susceptibility to tobacco smoke.

Cancer risk estimates for family members of a population-based family registry for breast and ovarian cancer.

Population-based breast and ovarian cancer family registries can facilitate studies to evaluate genetic and environmental factors in the etiology of these malignancies. The purpose of this study is to describe what is, as far as we know, the first population-based breast and ovarian cancer family registry and to estimate breast and ovarian cancer risk in relatives of breast and ovarian cancer probands. Population-based consecutive incident cases of breast and ovarian cancer were invited to participate in the University of California, Irvine breast and ovarian family registry. In this study, we report data on 1567 breast cancer and 328 ovarian cancer probands. The operational components of this family registry include enrollment of probands, family history interviewing, confidentiality, pathology, verification and review, biospecimen bank, statistical/genetic analysis, and special studies on positional cloning of known genes. All of the components are tracked through the University of California, Irvine Genetic Research Information System. In non-Hispanic-white breast cancer probands, relative risk (RR) of breast cancer in mothers and sisters is significantly elevated [RR = 1.7 and 95% confidence interval (CI) = 1.4-2.0 and RR = 2.8 and 95% CI = 2.3-3.3, respectively]. In families of ovarian cancer probands, mothers are at increased risk of ovarian cancer (RR = 4.6; 95% CI, 2.1-8.7). RR of breast cancer in mothers of Hispanic breast cancer probands is significantly elevated (RR = 4.9; 95% CI, 2.6-8.5). No elevation of breast or ovarian cancer risk was observed among relatives of Asian probands. In general, there is a decrease in RR among mothers and sisters with increase in age of onset of probands. In second-degree relatives and first cousins, the breast cancer hazards ratios increase with increase in the number of affected first-degree relatives and decrease with increase in age at onset of the proband.

A randomized, double blind, Phase III trial using oral beta-carotene supplementation for women with high-grade cervical intraepithelial neoplasia.

To evaluate the effect of daily beta-carotene (30 mg) versus placebo over a 2-year period on cervical intraepithelial neoplasia (CIN) 2 and 3 lesions. Human papillomavirus (HPV) typing was done to determine whether lesion regression was related to HPV. Micronutrient levels were measured to determine whether levels were predictive of regression. Variables that influence the risk of HPV infection and CIN, such as cigarette smoking and sexual behavior, were evaluated. Women were randomized to beta-carotene or placebo, with cytology and colposcopy every 3 months. Cervical biopsies were performed before treatment and after 6 and 24 months to evaluate response. Persistence of or progression to CIN 3 resulted in removal from the study, whereas treatment continued for 2 years on all others. The presence and type of HPV was determined by PCR. Response was defined as an improvement in CIN by 2 grades. Mantel-Haenszel chi(2) test was used to analyze response to treatment. Fisher's exact test was used to determine the effect of HPV and CIN grade on response Wilcoxon's rank-sum tests were used to compare micronutrient levels between groups. Twenty-one of 124 enrolled women were not randomized because they either moved, became pregnant, voluntarily withdrew, or the pathological review of their initial cervical biopsies did not confirm CIN 2 or 3. Of the remaining 103 women, 33 experienced lesion regression, 45 had persistent or progressive disease, and 25 women did not complete the study and were considered nonresponders in the final analysis. The overall regression rate (32%) was similar between treatment arms and when stratified for CIN grade. Data on 99 women with HPV typing showed that 77% were HPV-positive and 23% HPV-negative at enrollment. HPV-positive lesions were subdivided into indeterminate-, low-, and high-risk categories; the response rate was highest for women with no HPV detected (61%), lower for indeterminate/low-risk (30%), and lowest for high-risk (18%; P =.001). CIN regression was negatively correlated with retinol levels. In conclusion, beta-carotene does not enhance the regression of high-grade CIN, especially in HPV-positive subjects.

Characteristics of BRCA1 mutations in a population-based case series of breast and ovarian cancer.

Breast and ovarian cancers account for approximately 210000 newly diagnosed cases per year. More than half a million American women are estimated to be carriers of a breast cancer susceptibility gene. The purpose of this study was to assess the association of characteristics such as, age at diagnosis, race/ethnicity and family history of cancer with inherited BRCA1 mutations in a population-based sample of breast and ovarian cancer cases. No selection was made by race, age at diagnosis or positive family history of breast or ovarian cancer. The population under study was all breast cancer cases diagnosed in Orange County, CA, during the 1-year period beginning 1 March 1994 and all ovarian cancer cases diagnosed in Orange County during the 2-year period beginning 1 March 1994. This report focuses on the first consecutively ascertained 802 participating probands enrolled in the study, of which 9 were male breast cancer probands, 673 were female breast cancer probands and 120 were ovarian cancer probands. We observed 11 BRCA1 mutations or 1.6% (95% CI: 0.8-2.9) among the 673 female breast cancer probands and 4 BRCA1 mutations or 3.3% (95% CI: 0.8-8. 3) among the 120 ovarian cancer probands. No BRCA1 mutations were identified among the 98 non-white breast and ovarian cancer probands. The prevalence of BRCA1 mutations in non-Hispanic-white breast cancer cases below the age of 50 years was 2%. Positive family history of breast or ovarian cancers was significantly associated with BRCA1 mutation status among breast cancer probands. Similarly, positive family history of breast or ovarian cancer was significantly associated with BRCA1 mutation status among the ovarian cancer probands. In summary, we present results on the prevalence of BRCA1 mutations in a significantly larger sample of population-based breast and ovarian cancer cases than previously reported. The results indicate that, using a conservative approach to targeted genotyping of BRCA1, the frequency of mutations was consistent with those reported using similar methods of population-based case ascertainment.

The association of bladder cancer risk with ethnicity, gender, and smoking.

This study examined patterns of invasive bladder cancer by ethnicity and gender. Odds ratios were computed by comparing 593 patients of known smoking status and diagnosed during the period from 1984 to 1988 with a randomly selected referent group using a logistic regression model that adjusted for differences in age and current occupation. Age-adjusted incidence rates for non-Hispanic whites were approximately twice those of Hispanics and Asian and Pacific Islanders. After adjustment for smoking and occupational exposures, the risks did not differ significantly, indicating that ethnic differences in bladder cancer incidence may be related to smoking and occupational exposures. The odds ratio for males relative to females was 5.95 (95% confidence interval (CI), 4.36 to 8.12), after adjustment for ethnicity, smoking status, occupation, and age, suggesting that gender differences not previously identified may play an important role in the etiology of bladder cancer. Odds ratios associated with amount smoked per day, for current smokers relative to nonsmokers, ranged from 1.04 for those smoking less than 1 pack per day (95% CI, 0.62 to 1.71) to 6.84 for those smoking 2 or more packs per day (95% CI, 4.67 to 10.03).

Current estrogen-progestin and estrogen replacement therapy in elderly women: association with carotid atherosclerosis. CHS Collaborative Research Group. Cardiovascular Health Study.

The cardioprotective effects of combined estrogen/progestin replacement therapy have been questioned. Therefore, we have compared carotid arterial wall thickening and the prevalence of carotid stenosis in elderly women (> or = 65 years old) currently using replacement estrogen/progestins (E + P) with arterial pathology and its prevalence in women using unopposed estrogens (E). This cross-sectional study used baseline data from all 2962 women participating in the Cardiovascular Health Study, a population-based study of coronary heart disease and stroke in elderly adults. Users of hormone replacement therapy (HRT) were categorized as never (n = 1726), past (n = 787), current E (n = 280), or current E + P (n = 73). Maximal intimal-medial thicknesses of the internal and common carotid arteries and stenosis of the internal carotid arteries were measured by ultrasonography. Current E + P users resembled current E users in most respects, although some lifestyle factors were more favorable among E + P users. Current E + P use and current E use (as compared with no use) were associated with smaller internal carotid wall thicknesses (-0.22 mm; P = 0.003; and -0.09 mm; P = 0.05, respectively) and smaller common carotid wall thicknesses (-0.05 mm; P = 0.03; and -0.02 mm; P = 0.1, respectively) and lower odds ratios (OR) for carotid stenosis (> or = 1% vs. 0%); OR = 0.61; 95% confidence interval [CI]: 0.36 to 1.01; and OR = 0.91, 95% CI: 0.67 to 1.24, respectively), after adjustment for current lifestyle and risk factors. When both groups of current HRT users were compared, there were no significant differences in carotid wall thicknesses or prevalence of carotid stenosis. For this sample of elderly women, both current E + P therapy and current E therapy were associated with decreased measures of carotid atherosclerosis. These measures did not differ significantly between the two groups of HRT users.

Cancer prevention strategies: use of cancer prevention research registries.

We present a model to plan a rational strategy for cancer prevention that has two main functions--assessment and intervention. The assessment function includes three main components: to identify populations at high cancer risk, which may be due to their ethnic group, occupational and environmental exposures, family history, cigarette smoking, or other risk factors; to assess exposure to known carcinogens through the general and occupational environments, lifestyle factors, and the home as well as to document known carcinogens using human tissue banks and develop and validate questionnaires to target known risk factors for each of the most common cancers; and to conduct research studies of high-risk populations, including studies on mechanism and genetic testing. The intervention function includes three components: development of population-based intervention programs using the results from the research studies; evaluation of intervention programs; and modification of existing intervention programs and implementation of new ones. The above-proposed prevention strategy depends to a great extent on population-based cancer registries. Existing cancer registries around the United States should be strengthened and other dimensions should be added to their charge to augment their function in prevention research. To convert existing population-based cancer registries, particularly those that serve multiethnic and multicultural populations, into Cancer Prevention Research Registries (CPRRs), three types of data in addition to their existing required data complement should be incorporated. These are exposure information including occupational history, host factors information, and information about family history of cancer and associated conditions. The primary goal of the CPRRs should be to support cancer prevention research in its widest sense. Future research needs must be designed to investigate each of the components of the prevention strategy as well as its integrated performance. Regardless of what we do in the future, we must now promote healthier lifestyles, prevent exposure to known carcinogens, and improve early detection procedures.

Banking of human tissue for biomonitoring and exposure assessment: utility for environmental epidemiology and surveillance.

Human tissue banking could provide a tool to address a number of public health concerns. We can potentially use it to monitor trends in human exposures, serve as an early warning system for new environmental exposures, assess low-level exposures around hazardous waste and other point sources of pollutants, evaluate the effectiveness of regulatory programs, and study etiologies of diseases (e.g., childhood cancer and birth defects) that are likely to be related to the environment. This article discusses opportunities to establish human tissue banks in connection with pre-existing public health surveillance programs for cancer and adverse reproductive outcomes. This is a cost-effective way to conduct surveillance and enhances the ability to carry out epidemiologic studies. The article also discusses ethical issues that are particularly important for public health practice. One is the issue of risk communication and the need to explain risks in a way that provides people with the information they need to determine appropriate action on the individual and community levels. Second is the issue of environmental justice. We recommend early involvement of communities that are likely to be involved in tissue-banking projects and full explanation of individual and group social risks from their participation.