Race/ethnicity and OMB Directive 15: implications for state public health practice.

OBJECTIVES: This study assessed the impact of the Office of Management and Budget's (OMB's) 1997 revised standards for the collection of race and ethnicity data on state health departments, using the Massachusetts Department of Public Health (MDPH) as the primary example, and we make recommendations for states' implementation of these standards. METHODS: After analyzing the revised OMB standards, existing MDPH data sets were assessed for the impact of the revised standards on data collection, tabulation, analysis, and reporting for state health departments. RESULTS: The revised OMB standards will have an impact on the MDPH and other state health departments. Similarities and differences exist between federal and state health agencies regarding the purpose of data collection, tabulation, analysis, and reporting. These similarities and differences will affect state implementation of the revised OMB standards. CONCLUSIONS: States need to plan for the implementation of the revised OMB standards and to understand the impact of this revision on the collecting and reporting of public health data. The revised OMB standards will introduce added complexities to the collection and analysis of race and ethnicity data, but they will also produce a more nuanced understanding of the relationship of race and ethnicity to the health of the American people.

A polymorphic tetranucleotide repeat in the CYP19 gene and male breast cancer.

The CYP19 gene codes for the aromatase enzyme that is involved in the synthesis of oestrogens. This case-control study examines the relationship between a tetranucleotide repeat sequence in the CYP19 gene and the development of male breast cancer. No significant differences were found between male breast cancer cases and controls.

A polymorphism in the CYP17 gene is associated with male breast cancer.

The CYP17 gene codes for the cytochrome P450c17alpha enzyme that is involved in the synthesis of oestrogens. This case-control study from the South East of Scotland shows that a polymorphism of the CYP17 gene is associated with an increased risk of male breast cancer.

Organization, expression and polymorphism of the human persyn gene.

Persyn is a recently identified member of the synuclein family with a distinct pattern of expression during pre- and postnatal development of the mouse peripheral and central nervous systems. As with other synucleins, persyn is believed to be involved in the pathogenesis of human neurodegenerative diseases. However, in contrast to other synucleins, high levels of persyn mRNA expression were also found in advanced breast carcinomas, suggesting an involvement of the encoded protein in breast tumour progression. Here we have used an antibody specific to human persyn to demonstrate that the level of this protein is increased in ageing cerebral cortex and in breast tumours. We cloned, characterized and sequenced the human persyn genomic locus and localized it to the long arm of chromosome 10 in the q23.2-q23.3 region. Sequence information was used to search for specific mutations in the protein coding regions of persyn mRNA and the persyn gene in breast tumours and tumour cell lines. No tumour-specific mutations were found, but two linked polymorphisms in the coding region were detected, both in mRNA and exons III and IV of the gene. These results suggest that development of breast tumours correlates with overexpression of the wild-type persyn protein. Detailed characterization of the human persyn locus is important for further studies of the involvement of persyn in neurodegeneration and malignancy.

Loss of heterozygosity at 7q31 in breast cancer: results from an International Collaborative Study Group. The Breast Cancer Somatic Genetics Consortium.

Loss of heterozygosity (LOH) at 7q31 has been claimed to occur in over 80% of all breast cancers and to be of prognostic significance. This would make this genetic alteration the most common event observed in breast cancer to date. Others, however, have been unable to confirm this high incidence. In this multicenter study, we have complied LOH scorings for three polymorphic markers for 7q31-q32 in 683 breast tumors. Although some significant differences between centers existed, no center reported more than 40% LOH, and the average rate was 19%. Disease-free and overall survival of the patients whose tumors carried LOH at 7q31 did not differ significantly from those patients whose tumors showed retention of heterozygosity at 7q31. In a double-blind scoring of a subset of the raw data, an average discordant rate of LOH scoring of 12% was observed. While startling in itself, this was unable to explain the variation among centers, nor the difference with the initially reported high rate of LOH. We conclude that LOH at 7q31 is not important as a genetic alteration in breast cancer as originally suggested, nor a strong determinant of disease outcome.

Retrospective self-report of alcohol consumption: test-retest reliability by telephone.

The Timeline Follow-Back (TLFB) is an interview technique for obtaining detailed retrospective self-reports of alcohol consumption with excellent reliability for various composite variables when both administrations are in person. Because the telephone offers practical advantages over face-to-face interviewing for follow-up assessments in longitudinal studies of problem drinkers, this study was undertaken to compare the test-retest reliability of a 12-week TLFB interview when the second administration was by telephone to that when the second interview was in person. In addition, because the reliability of the TLFB has been previously assessed using composite variables, we examined the reliability of the TLFB at the item level. Research participants were 30 adult medical patients who drank frequently, and 75 college students who were problem drinkers. Test-retest reliability as measured by intraclass correlation was generally high, 0.79 or greater for the number of days of drinking > 6 standard drinks, 0.90 or greater for the number of abstinent days, and 0.80 or greater for the greatest number of drinks consumed on any 1 day, in both the most recent 4-week interval and in the entire 12-week interval. Test-retest correlation coefficients for composite variables derived from the interview data were not systematically affected by whether the second interview was in person or by telephone. Furthermore, item-level correlations were also substantial. Findings support the use of the telephone for follow-up interviews, potentially reducing costs of longitudinal studies and facilitating multisite studies with centralized data collection, and lend further general support to the reliability of the TLFB.

Loss of heterozygosity at 11q22 correlates with low progesterone receptor content in epithelial ovarian cancer.

Forty-seven epithelial ovarian cancers were analyzed for loss of heterozygosity (LOH) at D11S35 (11q22), close to the progesterone receptor (PR) gene, and for tumoral estrogen receptor (ER) and PR content. Thirty-eight of 47 tumors were informative, and, of these, 14 exhibited LOH. There was a significant association (P = 0.014) between D11S35 LOH and low tumoral PR content. For all informative tumors, there was no correlation between ER and PR; however, exclusion of tumors with LOH from the informative series revealed a linear correlation between tumoral ER and PR (P = 0.013), and established ER (P = 0.025) and PR (P = 0.05) content as significant factors in relation to patient survival. Patients with ER-rich tumors with D11S35 LOH had particularly poor survival compared with ER-rich, D11S35 heterozygous, no loss patients (P = 0.014). Analysis of the same tumors using two other microsatellites, D11S935 (11p13) and NM23 (17q22), showed no statistically significant relationships, although there were nonsignificant trends for the correlation of ER and PR expression in informative tumors without allele loss at these loci. We propose that genomic structural alteration at or close to the PR gene locus has biological and clinical sequelae in ovarian cancer.

Chromosome 11 allele imbalance and clinicopathological correlates in ovarian tumours.

Allele imbalance on chromosome 11 loci in ovarian cancer is a frequent event, suggesting the presence of tumour-suppressor genes for ovarian carcinogenesis on this chromosome. Ten highly polymorphic (CA) repeat microsatellites were used to determine allele imbalance in 60 primary ovarian tumours, including 47 epithelial ovarian cancers (EOCs). Forty EOCs (85%) showed allele imbalance at one or more loci, and in 39 of these (83%) the data suggested subchromosomal deletions: eight of 11p only; six of 11q only; and 25 of both 11p and 11q. Three consensus regions of deletion were indicated at 11p15.5-p15.3, 11q12-q22 and 11q23.3-q24.1. Allele imbalance at the 11q subtelomeric region (D11S912) correlated significantly with adverse survival, while imbalance at 11q14.3 and retention of heterozygosity at 11q22 (close to the site of the progesterone receptor gene) were associated with favourable clinicopathological features. The findings allow development of a preliminary model for the molecular evolution of epithelial ovarian cancer.

Overview of causes and costs of injuries in Massachusetts: a methodology for analysis of state data.

Massachusetts has developed the first State profile of the causes and costs of injury based on the national study, "Cost of Injury in the United States: A Report to Congress." Incidence of fatal injuries is based on Massachusetts data; nonfatal hospitalized injuries, on Massachusetts age and sex rates and U.S. cause data; and nonhospitalized injuries, on U.S. rates applied to Massachusetts census data. Lifetime costs per injured person are based on national data adjusted for higher personal health care expenditures and for higher mean annual earnings in Massachusetts. The estimated total lifetime cost for the 1.4 million injuries that occurred in 1989 is $4.4 billion--$1.7 billion for health care and $2.7 billion for lost earnings. Injuries attributed to motor vehicles and falls account for more than half of the total cost. The other cause categories are poisonings, fire-burns, firearms, drowings-near drownings, and other. For every person who dies from an injury, 17 people are hospitalized, and an estimated 535 people require outpatient treatment, consultation, or restricted activity. Development of a State-based cost report can be useful in monitoring the contribution of injuries to health status and in planning effective injury prevention strategies in a community-based health care system. The methodology described in this paper can be replicated by other States through accessing their State-specific mortality and hospital discharge data bases.

Breast cancer incidence, penetrance and survival in probable carriers of BRCA1 gene mutation in families linked to BRCA1 on chromosome 17q12-21.

Eight breast cancer pedigrees with a high probability of containing individuals with the BRCA1 gene mutation (odds 79.2-99.9 per cent) were identified through genetic linkage analysis using probes located within q12-22 on the long arm of chromosome 17. Some 102 female relatives were successfully typed with one or both of adjacent markers D17S588 and D17S579, and 41 were probable non-BRCA1 mutation carriers. Of the remaining 61 women classified as probable BRCA1 carriers, breast cancer was diagnosed in 35. As expected from epidemiological segregation analysis studies, 13 of these had bilateral disease. Approximately two-thirds of women unaffected by malignancy and alive at the time of observation were non-BRCA1 carriers. Lifetime disease penetrance of the BRCA1 gene was 88 per cent and this plateau was reached earlier (by age 65 years) than that estimated in segregation analysis. The survival curve of patients with breast cancer was less steep in BRCA1 gene carriers than that in the general population; 5-, 10- and 20-year survival rates unadjusted for non-cancer deaths were 83, 63 and 41 per cent respectively. The 5-year survival rate was significantly higher in BRCA1 carriers than that in an age-matched Scottish population (P < 0.05).

Genetic linkage analysis applied to unaffected women from families with breast cancer can discriminate high- from low-risk individuals.

Up to 20 per cent of cases of breast cancer diagnosed in women under the age of 45 years may be caused by an autosomal dominant gene. A present difficulty is differentiation of mutation carriers from non-mutation carriers in high-risk families. Genetic linkage analysis has been used to localize a susceptibility gene (BRCA1) on chromosome 17q12-21 between markers 42D6 and MFD188, a region 5-10 million base pairs in length. Odds in favour of linkage to this region were greater than 100,000:1 in 15 families with breast cancer. In eight families in which the probability of linkage was above 75 (range 79.2-99.9) per cent, 19 women were identified who were at high lifetime risk of breast cancer (range 80.6-87.2 per cent) and 37 whose risk was similar to that for the general population (range 9.8-16.4 per cent). Genetic risk prediction of this kind may enable high-risk screening clinic resources to be concentrated on those most likely to benefit.

Ethnicity, maternal risk, and birth weight among Hispanics in Massachusetts, 1987-89.

National data reveal that low birth weight and infant mortality rates among Hispanics are, in general, between the rates for whites and those for blacks. The question remains, do differences in low birth weight reflect distributions of known risk factors, or do ethnic differences persist after simultaneously adjusting for intervening variables? In this study, Massachusetts birth certificate data for 206,973 white non-Hispanic infants and 19,571 Hispanic infants are used to examine differences in low birth weight between white non-Hispanic and Hispanic infants, as well as variation among seven subgroups of Hispanic mothers--Puerto Rican, Dominican, Central American, South American, Mexican, Cuban, and other Hispanic. Regression analysis is used to estimate the association between risk factors and birth weight and the relative risk of low birth weight. Risk factors include ethnicity, demographic characteristics, biological factors, access to prenatal care, and infants' conditions. Results indicate substantial variation in mean birth weight, low birth weight, and levels of risk among Hispanic subgroups and between Hispanics and white non-Hispanics. Puerto Rican infants had the lowest mean birth weight and, in general, the highest level of risk factors in this population. None of the adjusted odds ratios for low birth weight for any Hispanic group was significantly elevated at the 95 percent level compared with white non-Hispanics. Findings in this study confirm the previous observations of the wide variation among Hispanic subgroups and the high level of risk among Puerto Ricans. Results of this study also raise some interesting questions about the differential relationship between ethnicity and birth weight, ethnicity and low birth weight, and the significance of maternal place of birth as a proxy measure of adaptation or acculturation.

Linkage of a major breast cancer gene to chromosome 17q12-21: results from 15 Edinburgh families.

DNA from members of 15 pedigrees each containing between three and eight cases of breast cancer have been collected from southeastern Scotland. Polymorphic markers on chromosome 17q were screened to locate a putative breast cancer gene by using DNA from relevant individuals within these families. Pairwise LOD scores were calculated for markers D17S74, NM23, D17S588, and D17S579. The maximal summated LOD for the 15 families was 5.44 at theta = .034, when D17S588 (42D6) was used. In these breast cancer families, a subset which did not give evidence for linkage to this region could be identified.

Maternal ethnicity and birthweight among blacks.

This paper examines the association of ethnicity and birthweight, adjusted for other maternal and infant characteristics, among black women who gave birth in Massachusetts from 1987 through 1989. Data are drawn from the standard certificate of live birth, which includes questions on race and ethnicity/ancestry as well as birthweight; maternal sociodemographic and biological characteristics; access to prenatal care; and infant characteristics. The study cohort consists of 18,571 black infants and a comparison group of 206,358 non-Hispanic white infants. Infants whose mothers reported their race as black were further categorized into six ethnic groups: American, Haitian, West Indian, Cape Verdean, Hispanic, and other black. In addition to descriptive analyses, we used multiple linear regression to measure the association between ethnicity, other characteristics, and birthweight; and we used multiple logistic regression to measure the odds ratio of low birthweight (ranging from 500 g to 2499 g) for the six black ethnic groups, adjusted for other characteristics. Results indicate that Americans have lower mean birthweight and generally higher levels of risk than other black ethnic groups. Compared to the reference group of non-Hispanic whites, Americans (OR = 1.49), other blacks (OR = 1.41), and West Indians (OR = 1.37) have significantly elevated relative risks of low birthweight.

Linkage mapping in familial breast cancer: improved localisation of a susceptibility locus on chromosome 17q12-21.

Fifteen pedigrees with a total of 75 cases of breast cancer, 10 of ovarian cancer and 53 of other cancers have been collected. Polymorphic markers on chromosome 17q have been screened to locate a putative breast-cancer gene using DNA from relevant individuals within these families. Pairwise LOD scores have been calculated for markers CMM86, NM23, 42D6 and MFD188. The maximal summated LOD for the 15 families is 4.45 at theta = 0.025 using 42D6. All cases of bilateral breast cancer and ovarian cancer appear to be linked to this region. Recalculating LOD scores on the assumption of linkage in these cases increases the maximal summated LOD to 5.62 at theta = 0.025 using 42D6. A genetic exclusion map of critical recombinants in linked families suggests that the gene is flanked by markers 42D6 and MFD188, a region 5 to 10 cm in length.

A significant proportion of patients with osteosarcoma may belong to Li-Fraumeni cancer families.

We studied the pedigrees of 17 index patients with osteosarcoma, recording malignant disease and cause of death for first- and second-degree relatives. There were seven cancers and five cancer deaths per 2151.5 person-years in first-degree relatives of osteosarcoma patients under the age of 50 years, a significantly greater incidence than in an age- and sex-matched population group (p < 0.001). This excess of malignancy was largely due to two families which fulfilled the criteria for the Li-Fraumeni cancer family syndrome. Both of these families were shown to have the genetic alterations in the p53 gene which have been implicated in this syndrome. Our study suggests that orthopaedic surgeons seeing new cases of osteosarcoma should arrange screening for familial malignancy.

A comparison of procedures for analysing microsatellite (CA)-repeat polymorphisms.

Dinucleotide repeat sequences ('microsatellites') have been used as polymorphic genetic markers following amplification in the polymerase chain reaction (PCR). We have compared several methods of analysing the PCR products. The most reliable and unambiguous results were obtained when the PCR products were probed with a specific dinucleotide repeat oligonucleotide, so that only the microsatellite-containing products were detectable.

Familial breast cancer.

Familial clustering of breast cancer has been recognised for over a century but until recently a genetic basis has been suspected rather than proven. Epidemiological studies have tended to support the view that an autosomal dominant gene, with high but incomplete penetrance, accounts for most breast cancer families. However, it is likely that several different predisposing genes are present within most populations. Difficulties arise in a conventional 'linkage mapping' approach to identifying these genes, first, because it is not clear that genetically homogeneous groups of families can be recognised on the basis, for example, of mean age of onset or pattern of other cancers within the kindred and, second, because breast cancer is so common (affecting almost one in twelve women) that large affected kindreds are likely to include an admixture of sporadic (non-genetic) cases. Cytogenetic and 'Loss of Heterozygosity' (LOH) studies in sporadic breast cancers have pointed to several candidate loci for breast cancer genes but there is no clear consensus from these two approaches that might direct attention to any prime target region. Recent reports of tight linkage between familial breast cancer (early onset) and breast/ovarian cancer (regardless of mean age of onset) and a locus on chromosome 17q21 defined by the anonymous probe CMM86, have not been confirmed in detail but have led to the identification of a locus some 15 Mb centromeric of CMM86 that gives a high positive lod at very low recombination fraction in fifteen Edinburgh breast and breast/ovarian cancer families. The disease in the majority of such families therefore appears to be attributable to a mutant gene at 17q12-21. A much smaller proportion of familial breast cancer is accounted for by mutations in the p53 gene (17p13). Not all such families fulfil the criteria for Li-Fraumeni syndrome and not all of the inherited mutations lie within exon 7 of p53. Counselling of members of breast cancer families becomes more exacting as these genetic lesions are identified. It is essential to extend the collection of data and tissue (blood or fixed pathology material) as widely as possible to confirm linkage to a specific locus within each individual kindred, to define the precise mutation and to establish the cancer phenotype and its penetrance. In the course of these studies a substantial population of women at high risk of breast (and other) cancer will be identified. Resources should be directed to this population so that optimum procedures for screening and prevention can be developed.