Epidemiology of breast cancer in a Mexican-American population.

This is a historical cohort study of breast cancer mortality in the Mexican-American community of Laredo, Texas. Included in this study were virtually all breast cancer deaths recorded in Laredo since 1875; controls matched to cases by age and birth year were drawn from the total population. Fertility history and family history of disease for cases and controls were retrieved from the genealogical data base reconstructed by our group from church and civil records for the whole city of Laredo. The findings of this study show an association between breast cancer risk and age at first birth. This study confirms familial risk to be a factor in breast cancer risk. Unlike postmenopausal breast cancer mortality in the total U.S. population, which has increased only slightly in the last 30-40 years, postmenopausal breast cancer death rates in Laredo have almost tripled since the 1940's.

Plasma lipids and diet of the Mvskoke Indians.

Plasma lipids, lipoproteins, and apolipoproteins were measured in 123 female and 57 male Mvskoke Indians, a population of American Indians with a high prevalence of non-insulin-dependent diabetes mellitus (NIDDM). Dietary patterns were assessed with a food-frequency questionnaire. There were no differences in total cholesterol, low-density-lipoprotein cholesterol (LDL-C), high-density-lipoprotein cholesterol (HDL-C), apolipoproteins A-I or B in female Indians with and without diabetes. In males with diabetes, however, LDL-C was lower. Triglyceride and fasting plasma glucose were higher in subjects with diabetes. Total cholesterol and LDL-C were lower and HDL-C was higher than age and sex-matched Lipid Research Clinics values, especially for subjects with diabetes. This is surprising given that the diet of Mvskoke Indians contains foods high in total fat, saturated fatty acids, and cholesterol. We may explain, in part, the low incidence of coronary heart disease in this population.

Hazards models for human population biology.

PIP: Population biologists often wish to examine the effects of continuous biological variables such as measures of growth, body size,nutritional status, and exposure to environmental risk factors on discrete vital events like birth, onset of disease, and death. Traditional statistical analyses are unable to accommodate some complexities which develop in studying such effects, including the censoring of observations and explanatory variables which change over time. Most traditional methods also provide only empirical rather than etiologic models of pertinent processes. Statistical techniques on hazards analysis deemed especially appropriate for studying biodemographic events and processes are reviewed. A general likelihood framework is also presented which allows the efficient estimation and testing of etiologic hazards models. Past attempts to model biological processes underlying age patterns of fertility and mortality are reviewed, while discussion is had on how the hazards framework may be adapted to study the quantitative genetics of vital events.^ieng

Optimizing utilization of DNA from rare or archival anthropological samples.

There is widespread interest in obtaining genetic samples from human populations worldwide for various studies of human genetic diversity. Many samples exist today only in the form of small, rare, irreplaceable, or archival samples, such as material from ancient bone, hair bulbs, or remnants of samples collected in the field decades ago for the purpose of protein and blood type analysis. Here, we describe the application of an approach to amplify DNA, which we call adapter attachment and amplification (AAA). This approach is useful for amplifying the genome in a reasonably representative way from small amounts of starting material using standard PCR-based methods. We apply a version of these methods to DNA extracted from washed red blood cells collected in the 1960s and 1970s in the Amazon basin. AAA and similar approaches may make the analysis of archival samples possible without exhausting that irreplaceable material and may lead to greatly improved efficiency in collecting and using new anthropological genetic samples.

Familial aggregation of cancer in Laredo, Texas: a generally low-risk Mexican-American population.

Genealogies for the Mexican-American city of Laredo, Texas, have been assembled by computer from individual civil and church records of birth, marriage, and death. Documentation is available on vital events in the lives of over 300,000 individuals, about 80% of the city population from 1870-1981. These data were collected to determine the degree to which death from cancer is more clustered in families than would be expected by chance alone; methods specific to this data base have been developed to accomplish this task. A statistically significant excess of familial cancer was observed overall when all cancer sites were pooled, but no evidence was observed for excess familial risk at single sites except for breast cancer and perhaps for ovarian cancer. The excess of breast cancer risk is comparable to that observed in other populations. A few site-combinations manifest excess familial risk, most notably those involving and dominated by breast cancer and certain digestive system sites. We do not confirm the degree of familiarity observed elsewhere for cancers of the lung, colorectum, stomach, or other sites in this generally low-risk population. Even where we find evidence of excess risk, the degree of excess is small and the number of multiply affected families too small to test etiologic models by segregation analysis. The absence of excess familial risk does not appear to be due to inadequate numbers of cases, since breast cancer is familial with no more occurrences in Laredo than other sites. These results differ to some extent from those found in a similar study of Utah Mormons, but it is unclear whether this is because of differences in risk patterns or statistical properties of the analytic methods used in the two studies.

Numerous members of the Sox family of HMG box-containing genes are expressed in developing mouse teeth.

We used RT-PCR to detect the expression in mouse molar and incisor tooth germs of 14 of the 19 known members of the Sox family of HMG box-containing transcription factors. These sequences fell into all 6 of the main subdivisions of the Sox family. In general, the relative transcript abundance of the different Sox genes is similar between molar and incisor tooth germs, although 3 low-abundance transcripts were found in only a single tooth type. The expression of Sox genes during tooth development has not been reported previously and further experiments will be required to determine their role in this process.

Long DOP-PCR of rare archival anthropological samples.

The application of molecular DNA technologies to anthropological questions has meant that rare or archival samples of human remains, including blood, hair, and bone, can now be used as a source of material for genetic analysis. Often, these samples are irreplaceable, and/or yield very small quantities of DNA, so methods for preamplifying as much of the whole genome as possible would greatly enhance their usefulness. DOP-PCR (degenerate oligonucleotide-primed polymerase chain reaction) is an amplification method that uses a degenerate primer and very low initial annealing temperatures to amplify the whole genome. We adapted a published DOP-PCR protocol to long PCR enzyme and amplification conditions. The effectiveness of these modifications was tested by PCR amplification of DOP-PCR products at a mixture of genomic targets including 66 different microsatellites, 11 Alu insertion polymorphisms, and variable-length segments of the human lipoprotein lipase gene (LPL). The selected microsatellite markers were chosen to represent every chromosome, with expected product sizes ranging from 150 base pairs to 8,000 base pairs in length, while the 22 Alu insertion polymorphisms were selected to reveal biases in the recovery of alleles of different sizes. To determine nucleotide sequence variation, 2 kilobases (kb) of the LPL gene in 30 Mongolian individuals were sequenced. All gene-specific targets from DOP-PCR product template were amplified. No unexpected polymorphisms in the sequence results attributable to the DOP-PCR step were found, and 93% to 95% of Alu genotypes that have been amplified from total genomic DNA were replicated. The incorrect typings were all due to the preferential amplification of the shorter of two possible alleles in individuals heterozygous for an Alu insertion and were all correctly typed on subsequent reamplification of the gene-specific PCR products. This method of whole-genome amplification promises to be an efficient way to maximize the genetic use of rare anthropological samples.

Reconstruction of genealogies from vital records: the Laredo Epidemiology Project.

The Laredo Epidemiology Project is a study of the patterns of degenerative disease, particularly cancer, in the families of Laredo, Texas. The genealogical history of Laredo was reconstructed by the grouping of 350,000 individual church and civil vital event records into multigenerational families, with record linkage based on matching names. Mortality data from city death records are mapped onto these pedigrees for analysis. This paper describes the creation of the data base and evaluation of the links.