Serum concentrations of DDE, PCBs, and other persistent organic pollutants and mammographic breast density in Triana, Alabama, a highly exposed population.

INTRODUCTION: Although some persistent organic pollutants (POPs) are considered human carcinogens, results from studies evaluating exposures and breast cancer risk have been inconsistent, potentially related to varying ages at exposure. Additionally, few studies evaluated the association between POPs exposure and mammographic breast density (MBD), an intermediate biomarker of breast cancer risk. We carried out a cross-sectional study to investigate associations between serum POPs concentrations and MBD measured in 1998 in female residents of Triana, Alabama, in a predominately African American population with high POPs exposures, particularly to p,p'-DDT (1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane). METHODS: We measured lipid-adjusted serum concentrations (ng/g lipid) of p,p'-DDT and its main metabolite p,p'-DDE (1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene), polychlorinated biphenyls (PCBs), ß-hexachlorocyclohexane (ß-HCCH), heptachlor epoxide, oxychlordane, trans-nonachlor, mirex, and aldrin for each woman in our study (n = 210). We also measured two MBD metrics, percent MBD (%MBD) and area of MBD (aMBD). Using adjusted Spearman correlation coefficients (rs) we evaluated correlations between %MBD and aMBD with individual POPs in the overall population and by age group (19-40, 41-54, and 55-91 years) and also estimated adjusted mean measures of MBD with 95% confidence intervals across tertiles of analytes using generalized linear models (GLM). We calculated p-values for multiplicative interaction by age group using GLM. Additional analyses excluded women with current hormone replacement therapy (HRT) use and evaluated early-life exposure (prior to age 18) during the heaviest contamination period in Triana (1947-90). RESULTS: Among all women, we found no correlation between p,p'-DDE and %MBD, but after age stratification and exclusion of HRT users, there was a suggestion of a difference by age group, with younger women having a weak positive correlation (rs = 0.12, p = 0.37) and older women having a weak negative correlation (rs = -0.12, p = 0.43); pinteraction = 0.06. In contrast, PCBs were weakly positively correlated with %MBD among all women, with the correlation magnitudes increasing after excluding current HRT users (rs-total PCBs = 0.17, p = 0.03). After age stratification and exclusion of HRT users, correlations for PCBs were higher among younger and middle-age women, with only a handful of these correlations being statistically significant. For ß-HCCH, the strongest finding was a negative correlation among older women (rs = -0.26, p = 0.07). Correlations were positive predominantly in the younger age group for heptachlor epoxide (rs = 0.27, p = 0.04), oxychlordane (rs = 0.35, p = 0.006), and trans-nonachlor (rs = 0.37, p = 0.003), and largely null for the middle and older age groups; pinteraction range: 0.03-0.05. Similar patterns were found in GLM analyses using tertiles of exposure and aMBD as the metric for MBD. Women exposed during the heaviest chemical contamination period in Triana prior to age 18 had positive correlations between %MBD and PCBs, heptachlor epoxide, mirex, oxychlordane, and trans-nonachlor. CONCLUSIONS: In this population, despite high exposures to p,p'-DDT and thus high serum concentrations of its main metabolite, p,p'-DDE, we did not find strong evidence of a positive association with MBD. In fact, there was some evidence of a negative association among older women for p,p'-DDE; a similar pattern was found for ß-HCCH. However, younger women with higher serum levels of PCBs, heptachlor epoxide, oxychlordane, and trans-nonachlor, who were likely exposed in early life, had higher MBD. These findings should be replicated in larger studies.

Agreement between self-reported birth weight and birth certificate weights.

Birth weight is emerging as a potentially important risk factor for several chronic diseases with adult onset, including breast cancer. Because participant recall is frequently used to gather data on early life exposures, it is essential that the accuracy of recall be assessed and validated. Self-reported birth weights and birth certificate weights were compared in women aged 35-51 years from the Western New York Exposures and Breast Cancer (WEB) Study, a population-based case-control study. A total of 180 participants had both birth certificate and interview data on birth weight. Participants reported birth weight to one of six categories (<5, 5-5.5, 5.6-7, 7.1-8.5, 8.6-10 and >10 lbs). The Spearman correlation for self-reported and birth certificate weights was 0.67. Sixty percent of participants reported weights with exact agreement with birth certificate; unweighted and weighted kappas (κ) were 0.39 and 0.68, respectively. Spearman correlations were similar for cases (0.67) and controls (0.68). Controls exhibited a significantly higher unweighted κ (0.51) than cases (0.27; P = 0.03), but weighted κ were not statistically different [controls, 0.73; cases, 0.64 (P = 0.32)]. Demographic and anthropometric characteristics were not different between participants who underreported, overreported, or correctly reported their birth weight for either cases or controls. Overall, the level of agreement for report of birth weight and actual birth weight was fair to moderate.

Jewish and Middle Eastern non-Jewish populations share a common pool of Y-chromosome biallelic haplotypes.

Haplotypes constructed from Y-chromosome markers were used to trace the paternal origins of the Jewish Diaspora. A set of 18 biallelic polymorphisms was genotyped in 1,371 males from 29 populations, including 7 Jewish (Ashkenazi, Roman, North African, Kurdish, Near Eastern, Yemenite, and Ethiopian) and 16 non-Jewish groups from similar geographic locations. The Jewish populations were characterized by a diverse set of 13 haplotypes that were also present in non-Jewish populations from Africa, Asia, and Europe. A series of analyses was performed to address whether modern Jewish Y-chromosome diversity derives mainly from a common Middle Eastern source population or from admixture with neighboring non-Jewish populations during and after the Diaspora. Despite their long-term residence in different countries and isolation from one another, most Jewish populations were not significantly different from one another at the genetic level. Admixture estimates suggested low levels of European Y-chromosome gene flow into Ashkenazi and Roman Jewish communities. A multidimensional scaling plot placed six of the seven Jewish populations in a relatively tight cluster that was interspersed with Middle Eastern non-Jewish populations, including Palestinians and Syrians. Pairwise differentiation tests further indicated that these Jewish and Middle Eastern non-Jewish populations were not statistically different. The results support the hypothesis that the paternal gene pools of Jewish communities from Europe, North Africa, and the Middle East descended from a common Middle Eastern ancestral population, and suggest that most Jewish communities have remained relatively isolated from neighboring non-Jewish communities during and after the Diaspora.

Considerations in adding mutation detection services to a sequencing core facility.

Because analysis of single nucleotide polymorphisms (SNPs) can be invaluable in understanding genomic variation and the genetic basis of disease, there is a need for high-throughput, high-accuracy mutation detection methods for identifying SNPs. A sequencing core facility can enhance the services it offers by providing genome analysis methods to search for informative SNPs. Denaturing high-performance liquid chromatography and single-strand conformation polymorphism analysis are methods of mutation detection that are amenable to a sequencing core environment. They are useful for screening large sample sets to identify novel SNPs, eliminating the need to sequence every sample in the set. These methods allow analysis of more samples than would otherwise be economically feasible by sequencing alone.

The geographic distribution of human Y chromosome variation.

We examined variation on the nonrecombining portion of the human Y chromosome to investigate human evolution during the last 200,000 years. The Y-specific polymorphic sites included the Y Alu insertional polymorphism or "YAP" element (DYS287), the poly(A) tail associated with the YAP element, three point mutations in close association with the YAP insertion site, an A-G polymorphic transition (DYS271), and a tetranucleotide microsatellite (DYS19). Global variation at the five bi-allelic sites (DYS271, DYS287, and the three point mutations) gave rise to five "YAP haplotypes" in 60 populations from Africa, Europe, Asia, Australasia, and the New World (n = 1500). Combining the multi-allelic variation at the microsatellite loci (poly(A) tail and DYS19) with the YAP haplotypes resulted in a total of 27 "combination haplotypes". All five of the YAP haplotypes and 21 of the 27 combination haplotypes were found in African populations, which had greater haplotype diversity than did populations from other geographical locations. Only subsets of the five YAP haplotypes were found outside of Africa. Patterns of observed variation were compatible with a variety of hypotheses, including multiple human migrations and range expansions.