A candidate gene approach to searching for low-penetrance breast and prostate cancer genes.

Most cases of breast and prostate cancer are not associated with mutations in known high-penetrance genes, indicating the involvement of multiple low-penetrance risk alleles. Studies that have attempted to identify these genes have met with limited success. The National Cancer Institute Breast and Prostate Cancer Cohort Consortium--a pooled analysis of multiple large cohort studies with a total of more than 5,000 cases of breast cancer and 8,000 cases of prostate cancer--was therefore initiated. The goal of this consortium is to characterize variations in approximately 50 genes that mediate two pathways that are associated with these cancers--the steroid-hormone metabolism pathway and the insulin-like growth factor signalling pathway--and to associate these variations with cancer risk.

A prospective cohort study of oral contraceptives and breast cancer.

In 1970 a questionnaire was sent to 97,300 married women aged 25-50 years residing in eastern Massachusetts information was requested on use of oral contraceptives (OC), education, and gynecologic and reproductive histories. Subsequent questionnaires were sent in 1973 and 1979 to a subset of the original cohort (37,000) to obtain recent information. Surveillance of 34 hospitals disclosed 622 cases of breast cancer among respondents diagnosed in a 6 1/2-year period. The rate ratio of breast cancer associated with any use of OC was 0.84 (95% confidence limits: 0.7, 1.1). Although certain subgroups users experienced significantly lower rates of hospitalization for breast cancer than did nonusers (including users aged 25-29, those for whom less than or equal to 5 yr had passed since first use, women with ages at birth of first child either before 25 or after 30, and women who first used OC after the birth of the first child), the risk of breast cancer OC after the birth of the first child), the risk of breast cancer was not consistently lower among users of OC. Among nulliparous women, the rate ratio associated with use of OC was 2.1 (0.9, 5.0).

Estrogen replacement therapy and benign breast disease.

The relationship between estrogen replacement therapy (ERT) and the risk of benign breast disease (BBD) was examined among 929 postmenopausal cases and 846 postmenopausal controls identified through a large breast cancer screening program. Prior use of ERT among postmenopausal women was associated with an increased risk of both fibrocystic breast disease [odds ratio (OR) = 1.4; 95% confidence interval (Cl) = 1.1-1.8] and fibroadenoma (OR = 1.6; Cl = 0.8-3.5). The risk of all BBD rose with increasing years of use (OR = 1.9 for greater than or equal to 15 yr of total use) and with years since initial use (OR = 1.6 for greater than or equal to 15 yr since first use). Among users of the conjugated estrogen Premarin, increased risks were found at all but the lowest dose. Finally, risks associated with ERT were higher in women with a bilateral oophorectomy than in other postmenopausal women. These results suggested, overall, an increased risk of BBD associated with ERT.

Oral contraceptive use and fibrocystic breast disease of different histologic classifications.

The relationship between oral contraceptive (OC) use and occurrence of fibrocystic breast disease (FBD) of different histologic classifications was evaluated with data from a cohort study. Biopsy specimens from 232 women with FBD were classified into different atypia categories. In 96 matched pairs of OC users and nonusers, atypia scores were lower in users than in nonusers. Women without breast diseases (500 OC users and 500 nonusers) were sampled from the original cohort to form a two-stage "anamorphic" study with the 232 cases of FBD. The previously shown inverse association between OC use and FBD occurrence was present and increased with increased length of OC use. However, the "protective effect" of OC use did not vary for different histologic classifications of FBD. The findings from both paired and anamorphic analyses of the data are not consistent with the hypothesis that the use of OC is associated with decreased frequency only of FBD with minimal epithelial atypia.

Cancer in south Florida Hispanic women. A 9-year assessment.

BACKGROUND: Cancer incidence varies among race and ethnic subgroups. Relatively little information exists on cancer among Hispanics, and none of it it stratified by race. METHODS: To explore and compare cancer incidence rates of each site of cancer among white Hispanic, white non-Hispanic, black Hispanic, and black non-Hispanic women in Dade County, South Florida, we accessed 9 years of cancer incidence data. Dade County's Hispanic population is the second largest of any US county. For each site, incidence rates, rate ratios, and 95% confidence intervals are presented. RESULTS: Among white Hispanics, there were statistically significant lower rates of cancers of the oral cavity, esophagus, colon, pancreas, lung, breast, ovary, bladder, kidney, melanoma, Kaposi's sarcoma, and non-Hodgkin's lymphoma than among white non-Hispanics. Black Hispanics had significantly lower rates of cancers of the oral cavity, stomach, rectum, lung, cervix, and bladder than black non-Hispanics. However, white Hispanic women had significantly higher rates of cancers of the liver, gallbladder, and uterine cervix than white non-Hispanic women. No in situ breast cancer cases among blacks of either ethnic subgroup was found. CONCLUSION: Both white Hispanic and black Hispanic women generally had lower rates of cancer than their race-specific non-Hispanic counterparts. However, incidence rates among Hispanics differ substantially by race; failure to distinguish them may lead to erroneous conclusions.

Cancer among Hispanic males in south Florida. Nine years of incidence data.

BACKGROUND: Dade County (Florida) is the largest county in the United States in which a majority of the population is Hispanic. To describe and compare cancer incidence among white and black Hispanic and non-Hispanic males in South Florida and to identify those sites showing important racial-ethnic differences between sub-groups, incidence rates were determined from 9 years of prospective population-based cancer surveillance data. METHODS: All incident cancer cases diagnosed among male residents of Dade County for the period January 1, 1981, through December 31, 1989, were obtained from the statewide tumor registry for Florida, the Florida Cancer Data System. Race- and ethnic-specific age-standardized incidence rates and standardized rate ratios to compare rates among racial-ethnic subgroups for each site are presented. RESULTS: Compared with white non-Hispanics, white Hispanic males had significantly higher rates of cancers of the liver, gallbladder, nasal cavity, penis, and thyroid; acute lymphocytic leukemia; and Kaposi's sarcoma. Significantly lower rates were found for cancers of the esophagus, stomach, colon, rectum, pancreas, lung, testes, bladder, and kidney, and for mesothelioma, melanoma, non-Hodgkin's lymphoma, and chronic lymphocytic leukemia. Black Hispanics had significantly lower rates only of cancers of the esophagus, lung, and prostate than did black non-Hispanics. CONCLUSION: Differences were found in incidence rates by race-ethnicity; while incidence rates for most sites among white Hispanic males were lower than among white non-Hispanics, higher rates for several sites are of particular concern and merit further investigation to determine differences in risk factors and exposures.

Epidemiology of cancer among Hispanics in the United States.

BACKGROUND: There are very limited data on cancer among U.S. Hispanics. The data that are available seldom appear outside individual registry reports. Without coalescing and assessing such information, the epidemiology of cancer among Hispanics cannot be understood. PURPOSE: This article presents an overall view of the epidemiology of cancer among Hispanic populations in the United States. METHODS: Major types of cancer were reviewed from geographic areas with 1) large Hispanic/Latino populations and 2) population-based cancer registries that cover 68% of the U.S. Hispanic population. Age-standardized rates, standardized rate ratios, and ranks of the top cancers are presented for Hispanics and non-Hispanics by sex. RESULTS: Hispanic men had consistently lower rates of cancers of the lung, prostate, colon, rectum, and oral cavity as well as of melanoma and non-Hodgkin's lymphoma than non-Hispanic men. Among Hispanic men, higher rates were observed for cancers of the stomach, liver, and gallbladder. Compared with the rates in non-Hispanic women, Hispanic women had consistently lower rates of cancers of the breast, colon, rectum, endometrium, lung, ovary, and oral cavity, non-Hodgkin's lymphoma, and melanoma and higher rates of cancers of the uterine cervix, stomach, liver, and gallbladder. Perhaps more importantly, however, was that, within U.S. Hispanic populations, the top five sites of cancer for women were breast, colon, lung, cervix, and uterine corpus. For men, the top sites were usually prostate, lung, colon, stomach, and rectum. Furthermore, some geographic areas showed differences in the order of importance within these five sites, while in other areas, the top five cancers for Hispanic men included kidney and bladder cancers, liver cancer, and non-Hodgkin's lymphomas. For women, other leading cancers mentioned were ovarian cancer, non-Hodgkin's lymphoma, and gallbladder cancer. CONCLUSIONS: Hispanics had consistently lower rates of breast, lung, prostate, and colon cancers than non-Hispanics. In some geographic regions, however, differences in cancer incidence rates with respect to specific sites existed between the heterogenous Hispanic populations. Furthermore, the rankings demonstrated that, even if Hispanics have lower rates of the most common cancers than non-Hispanics, such sites are still the most important cancers among Hispanic populations. IMPLICATIONS: Cancer is a major problem among U.S. Hispanic populations. The information given in this article can be used to develop etiologic studies and cancer control interventions. Data limitations and recommendations for improving data quality are presented.

A prospective cohort study of oral contraceptives and cancer of the endometrium.

A prospective cohort study of approximately 97 300 women was conducted in eastern Massachusetts. Information on use of oral contraceptives, and on gynaecological and reproductive histories was sought through mailed questionnaires, while newly diagnosed cases of cancer of the endometrium were identified from records of 34 area hospitals. Oral contraceptive (OC) use was associated with some increase in endometrial cancer rates (standardized rate ratio = 1.4; 95% confidence interval = 0.9-2.4), although the risk did not vary consistently by length of use, years since first use, or age at initial use. Although some subgroups of users had rates of disease higher than among nonusers, there was little to suggest a consistent association between OC use and incidence of endometrial cancer.

PIP: A prospective cohort study of approximately 97,300 women was conducted in eastern Massachusetts. Information on the use of oral contraceptives (OCs), and on gynecological and reproductive histories was sought through mailed questionnaires, while newly diagnosed cases of endometrial cancer were identified from records of 34 area hospitals. OC use was associated with some increase in endometrial cancer rates (standardized ratio rate-1.4; 95% confidence interval=0.9-2.4), although the risk did not vary consistently by length of use, years since 1st use, or age at initial use. Although some subgroups of users had rates of disease higher than among nonusers, there was little to suggest a consistent association between OC use and incidence of endometrial cancer.

Social networks and cancer screening in four U.S. Hispanic groups.

BACKGROUND: Evidence shows that social relationships play an important role in health and health behavior. We examined the relationship between social networks and cancer screening among four U.S. Hispanic groups. METHODS: We used telephone surveys to collect data in eight U.S. regions that have concentrations of diverse Hispanic-origin populations. We interviewed 8903 Hispanic adults, for a response rate of 83%; analysis was restricted to the 2383 women aged > or =40. As a measure of social integration, we formed a social network index from items on the number of close relatives and friends, frequency of contact, and church membership. We used logistic regression to estimate the effects of social integration on screening, adjusting for sociodemographic factors. RESULTS: Among Mexican, Cuban, and Central-American women, the effect of social integration on mammography screening was slight. The odds ratios (OR) per unit change in social integration category ranged from 1.16 to 1.22 with confidence intervals (CI) that overlapped with the null. For Pap smear screening, the effect was strongest among Mexican-American women (OR=1.44, 95% CI=1.21 to 1.72), but also evident among Central-American women (OR=1.22, 95% CI=0.72 to 2.06) and Cuban women (OR = 1.25, 95% CI = 0.81 to 1.93). Among Puerto Rican women, social integration had no effect on either mammography (OR=1.03) or Pap smear screening (OR=1.08). CONCLUSIONS: Independent of socioeconomic factors, social integration appears to influence cancer screening participation of Hispanic women. The modest effect is not universal across Hispanic groups and was stronger for Pap smear than for mammography screening behavior. Researchers should recognize Hispanic group differences in social network characteristics and the potential of social networks to change screening behavior.

Age at first birth, parity, and breast cancer risk.

The roles of age at first full-term birth and parity as risk factors for breast cancer were examined as part of a large prospective cohort study of oral contraceptive use. Compared to women who first gave birth before age 20 years, women with a first birth between age 20 and 24 years had an SRR of 1.70, and women with first births between age 25 and 29 years and over age 29 had SRRs of 2.19 and 3.18, respectively. Increased incidence rates of breast cancer fell with increasing parity, although standardization for age at first birth diminished the importance of the former as an independent indicator of breast cancer risk.

Differences in stage at presentation of breast and gynecologic cancers among whites, blacks, and Hispanics.

BACKGROUND: One of the possible assumptions for the higher mortality from cancer of blacks versus whites is that blacks tend to be diagnosed relatively more often with later stage disease. This study examined the stages at diagnosis for female breast cancer and other gynecologic cancers among blacks, non-Hispanic whites, and Hispanic whites. METHODS: Data for Dade County were analyzed in this study, which was based on the tumor registry data from the Florida Cancer Data System from 1981-1989. The stages at diagnosis were classified as in situ, local, regional, and distant according to the International Classification of Diseases for Oncology coding rules. RESULTS: The percentage of early stage diagnoses (in situ and local stage) was significantly lower among blacks and Hispanic whites than among non-Hispanic whites, but only for breast and cervical cancer. There was a significant increase in the percentage of early stage diagnoses of breast cancer among all three groups during 1981-1989, whereas this increase was found only in Hispanic whites for cervical cancer. The percentage of in situ cervical cancers was much lower in women older than age 45, especially among women older than age 65, in all three groups. CONCLUSIONS: These data suggest that screening programs need to be targeted differently for specific age and ethnic groups.

Correlates of participation and willingness to participate in anti-tobacco activities among 4th-7th graders.

The purpose of this study was to identify factors associated with participation and willingness to participate in anti-tobacco community activities in 4-7th grade students. A probability sample was drawn from seven regions in Florida (n = 1219). Telephone interviews assessed socioeconomic status, tobacco use, knowledge, and attitudes, and exposure to anti-tobacco school education and media campaigns. Factors related to both participation and willingness included: parental discussion of tobacco use, exposure to school courses with anti-tobacco curricula and a belief that youth could convince their friends to stop smoking. Additional participation correlates included: parental smoking status and student government activity participation. Additional willingness correlates included: exposure to anti-tobacco television campaigns, liking school, and several tobacco-related knowledge and attitudinal questions. These findings suggest that exposure to community-based tobacco control programs and family discussion of tobacco use is associated with regular participation and/or willingness of youth to participate in anti-tobacco activities.

Cancer among Haitians in Florida.

Data on cancer rates from West Indian populations are scarce, and to the authors' knowledge there are no published data on cancer rates and distributions among Haitians. Proportional distributions of cancers among three groups of patients living in Florida were compared: Haitian born blacks, United States born blacks, and non-Haitian Caribbean born blacks. The incidence rate of cancer of the cervix among the Haitian and United States born black groups was also compared. Increased rates of certain malignancies associated with viral infection or immunodeficiency were found in the Haitian group. These tumors were hepatocellular carcinoma, nasopharyngeal carcinoma, reticulum cell sarcoma, Kaposi's sarcoma, and carcinoma of the uterine cervix. The age-adjusted incidence rate of carcinoma of the cervix was especially high among Haitian women even with a liberal estimate of the female Haitian population from whom the cases were drawn. Except for cancer of the cervix, the numbers of cancers of interest were small, and age-adjusted incidence rates were not calculated. Continued epidemiological study of larger numbers of patients is needed to evaluate these findings further.

Age at first birth and breast atypia.

The relation between age at first birth and the occurrence of fibrocystic breast disease of different atypia subtypes was evaluated using data from a cohort study of the health effects of oral-contraceptive use. Multivariate case-control analysis was performed on 218 parous women with biopsied fibrocystic disease and 928 parous controls. Fibrocystic breast disease, as a whole and as atypia subtypes, was found to be unrelated to age at first birth. Furthermore, the estimated effect of age at first birth did not vary from one atypia subtype to another. Women with high parity were found to be at decreased risk of fibrocystic breast disease compared to those with low parity. Age at completion of education, used as an indicator of socioeconomic status, was found to be moderately associated with fibrocystic breast disease. The estimated effect of parity and age at completion of education also did not vary among subtypes. More epidemiologic studies specific to histopathologic classifications of benign breast disease are called for.

The effect of marital status on survival in late-stage cancer patients: an analysis based on surveillance, epidemiology, and end results (SEER) data, in the United States.

Recently findings that marital status is associated with survival in patients with late-stage prostate cancer led to an examination of the generalizability of this association for all cancers. We restricted the investigation to patients with late-stage cancer using population-based data collected from 261,070 patients with late-stage cancer at multiple sites in the United States to determine relations between marital status and survival. After controlling for age, race, and treatment, married patients with cancers of all major primary sites had significantly better survival than single, separated, divorced, or widowed patients. Although single and widowed patients had the poorest prognosis in general, single patients appeared to show the most consistently poor survival across the different types of cancers. Survival differences by marital status were more pronounced in men than in women. This observation raises the possibility that some characteristics associated with being married delay death from cancer. These findings require investigators to ask new questions about the effect of being married and its possible correlates, such as general health status, access to health care, and socioeconomic status. Known correlates of marital status, such as available social support and social isolation also merit attention in relation to these findings.

Influence of a counteradvertising media campaign on initiation of smoking: the Florida "truth" campaign.

OBJECTIVES: The purpose of this study was to assess the short-term effects of television advertisements from the Florida "truth" campaign on rates of smoking initiation. METHODS: A follow-up survey of young people aged 12 to 17 years (n = 1820) interviewed during the first 6 months of the advertising campaign was conducted. Logistic regression analyses were used to estimate the independent effects of the campaign on smoking initiation while other factors were controlled for. RESULTS: Youths scoring at intermediate and high levels on a media effect index were less likely to initiate smoking than youths who could not confirm awareness of television advertisements. Adjusted odds ratios between the media index and measures of initiation were similar within categories of age, sex, susceptibility, and whether a parent smoked. CONCLUSIONS: Exposure to the "truth" media campaign lowered the risk of youth smoking initiation. However, the analysis did not demonstrate that all such media programs will be effective.

Estimates of trace element intakes in Chinese farmers.

Epidemiologic data on the average daily human dietary intake of the trace elements nickel, cadmium, molybdenum and silicon are scarce, worldwide, primarily because foods consumed vary widely over days and seasons. Available full year food allocation records for farmers in rural areas of China provide an unique opportunity to estimate dietary trace elements. In 1988, we measured the concentration of zinc, copper, iron, cadmium, nickel, molybdenum, silicon and selenium in different foods by using food samples collected from 232 villages (distributed among 21 communes). These measurements, combined with the food consumption information from existing food allocation records in each commune for an entire year, allowed us to estimate the average daily consumption of these trace elements by Chinese farmers. With one exception (an association of zinc and esophageal cancer), the variation of dietary trace elements did not show any association with mortality from several common diseases. The estimates for some of the dietary trace elements from some subpopulations were either less or more than current recommendations. No increases in mortality were found, however, from diseases normally associated with either dietary deficiencies or excesses of these elements.

Plasma zinc, copper, copper:zinc ratio, and survival in a cohort of HIV-1-infected homosexual men.

A prospective cohort study of 121 HIV-1-positive homosexual men was conducted in Miami, Florida, U.S.A. to evaluate the associations between plasma zinc and copper levels and mortality. Plasma zinc and copper levels were measured at baseline and then at semiannual visits. Zinc inadequacy and copper inadequacy were defined as plasma zinc levels <75 (microg/dl) and plasma copper levels <85 (microg/dl), respectively. HIV-1-related deaths were confirmed by review of death certificates. Cox proportional hazards regression models with time-dependent covariates were used to estimate the relative risks of zinc and copper inadequacy on mortality. Over the average course of the 3.3-year follow-up, 19 participants (16%) died of HIV-1-related causes. After adjustment for potential confounders, including low CD4+ cell counts and antiretroviral therapy, zinc inadequacy and copper:zinc ratio >1 (i.e., plasma copper level greater than plasma zinc level) were associated with increased mortality (relative risks [RRs]; 95% confidence intervals [CIs], 4.98, 1.30-19.00 and 8.28, 1.03-66.58, respectively). A negative association was also observed between plasma zinc levels and mortality (RR 0.94; 95% CI, 0.91-0.98). Plasma levels of copper were not significantly associated with mortality. These results suggest that plasma zinc inadequacy or the plasma copper:zinc ratio may be useful predictors of survival in HIV-1 infection. The latter appears to be a stronger predictor.

Community activism relating to a cluster of breast cancer.

In 1985, residents of a suburban community in South Florida became concerned when several young women were diagnosed with breast cancer. First as individuals, then through a community-based effort, they attempted to gain attention and action on what they believed to be a cluster of breast cancer. Through their efforts to find out whether some agent or toxic exposure existed in the community that might have caused breast cancer, the women formed a community-based organization. This paper describes the activism of the women to resolve the issue through an epidemiologic study of the breast cancer occurrence in their community. Furthermore, it substantiates the need and role of rational community response in resolving community threats and concerns.

The role of the physician as an information source on mammography.

PURPOSE: The value of mammography for asymptomatic women younger than 50 years of age has been under debate, and it had been suggested that each woman should decide for herself whether to start having mammograms in her 40s. This decision-making process requires women to have knowledge of screening guidelines. This study reported key determining informational factors that led women age 40 and older to obtain a mammogram. DESCRIPTION OF STUDY: To examine the relationship between sources of information and utilization of mammography, the authors conducted a communitywide telephone survey, in English and Spanish, of a stratified random sample of 999 white, black, and Hispanic women in Dade County, Florida. The survey was designed to measure knowledge, attitudes, practices, and beliefs about breast cancer, its prevention, and its early detection. Data for 784 women 40 years and older are analyzed and reported here. RESULTS: The most commonly cited source of information was the media (90.2%). In a logistic regression, having had a checkup in the past year was the strongest predictor of having had a recent mammogram as opposed to a distant one (OR 4.17; 95% CI 2.92-5.95). Women who named their physician as an important source of information about health and prevention were also more likely to have had a recent examination (OR 1.85; 95% CI 1.27-2.69). CLINICAL IMPLICATIONS: This analysis of the relationship between the source of information and utilization of mammography suggests that physicians, as sources of information, serve to motivate women to obtain a mammogram. This is true even after taking into account the patient's age and utilization of the healthcare system for preventive care in general. For this reason, it is imperative that clinicians be aware of national guidelines for breast cancer screening; of the risks and benefits of screening measures; and of the implications of a positive and negative test result. In addition, clinicians must realize the importance of follow-up to remind the patient to obtain a mammogram or other screening test and should develop strategies to provide this service.