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Prostate cancer exerts a greater toll on African American men than on White men of European descent (hereafter referred to as European American men): the disparity in incidence and mortality is greater than that of any other common cancer. The disproportionate impact of prostate cancer on Black men has been attributed to the genetics of African ancestry, to diet and lifestyle risk factors, and to unequal access to quality health care. In this Review, all of these influences are considered in the context of the evolving understanding that chronic or recurrent inflammatory processes drive prostatic carcinogenesis. Studies of inherited susceptibility highlight the contributions of genes involved in prostate cell and tissue repair (BRCA1/2, ATM) and regeneration (HOXB13 and MYC). Social determinants of health appear to accentuate these genetic influences by fueling prostate inflammation and associated cell and genome damage. Molecular characterization of the prostate cancers that arise in Black versus White men further implicates this inflammatory microenvironment in disease behavior. Yet, when Black and White men with similar grade and stage of prostate cancer are treated equally, they exhibit equivalent outcomes. The central role of prostate inflammation in prostate cancer development and progression augments the impact of the social determinants of health on disease pathogenesis. And, when coupled with poorer access to high-quality treatment, these inequities result in a disparate burden of prostate cancer on African American men., Introduction In the United States, prostate cancer is one of the most common cancers afflicting aging men (1, 2). Autopsy studies hint that as many as 59% of men aged [...]

Many studies have shown that primary prostate cancers are multifocal [1-3] and are composed of multiple genetically distinct cancer cell clones [4-6]. Whether or not multiclonal primary prostate cancers typically give rise to multiclonal or monoclonal prostate cancer metastases is largely unknown, although studies at single chromosomal loci are consistent with the latter case. Here we show through a high-resolution genome-wide single nucleotide polymorphism and copy number survey that most, if not all, metastatic prostate cancers have monoclonal origins and maintain a unique signature copy number pattern of the parent cancer cell while also accumulating a variable number of separate subclonally sustained changes. We find no relationship between anatomic site of metastasis [7] and genomic copy number change pattern. Taken together with past animal and cytogenetic studies of metastasise and recent single-locus genetic data in prostate and other metastatic cancers [8-10] these data indicate that despite common genomic heterogeneity in primary cancers, most metastatic cancers arise from a single precursor cancer cell. This study establishes that genomic archeology of multiple anatomically separate metastatic cancers in individuals can be used to define the salient genomic features of a parent cancer clone of proven lethal metastatic phenotype., We isolated DNA from 94 anatomically separate cancer sites in 30 men who died from metastatic prostate cancer (Fig. 1a) and analyzed it by chromosomal metaphase-based comparative genomic hybridization (cCGH), [...]

Genetics, lifestyle, and diet probably contribute to the development of prostate cancer in most men. Carcinogens in cooked meats may be a risk factor and vegetables may prevent prostate cancer. Research has also shown that infection or inflammation in the prostate may be a precursor of prostate cancer. Genes associated with prostate cancer include RNASEL, MSR1, AR, CYP17, SRD5A2, GSTP1, NKX3.1, PTEN, and CDKN1B.

Remediation of Massachusetts' New Bedford Harbor does not appear to significantly affect the levels of polychlorinated biphenyls (PCBs) within surficial sediment. The estuary is a Superfund site and is being monitored for the effects of the remediation effort. An analysis of the data using exploratory statistical techniques and a qualitative graphical technique helped determine subtle changes caused by the remediation effort that were not evident with measurements by traditional methods.

A long-term monitoring scheme was developed in an effort to evaluate the efficiency of a multistage Superfund remediation program adopted at the New Bedford Harbor to address the site's polychlorinated biphencyl (PCB) contamination problems. The scheme integrates a number of graphical and statistical methods necessary in quantifying the spatial and temporal variability of PCB concentration in the place. Results revealed that low molecular weight PCBs have been transported in farther places as a result of the bioremediation program.

Chronic oxidative stress may play a critical role in the pathogenesis of many human cancers. Here, we report that mouse embryonic stem (ES) cells deficient in DNA mismatch repair responded abnormally when exposed to low levels of ionizing radiation, a stress known to generate oxidative DNA damage. ES cells derived from mice carrying either one or two disrupted Msh2 alleles displayed an increased survival following protracted exposures to low-level ionizing radiation as compared with wild-type ES cells. The increases in survival exhibited by ES cells deficient in DNA mismatch repair appeared to have resulted from a failure to efficiently execute cell death (apoptosis) in response to radiation exposure. For each of the ES cell types, prolonged low-level radiation treatment generated oxidative genome damage that manifested as an accumulation of oxidized bases in genomic DNA. However, ES cells from [Msh2.sup.+/-] and [Msh2.sup.-/-] mice accumulated more oxidized bases as a consequence of low-level radiation exposure than ES cells from [Msh2.sup.+/+] mice. The propensity for normal cells with mismatch repair enzyme deficiencies, including cells heterozygous for inactivating mismatch repair enzyme gene mutations, to survive promutagenic genome insults accompanying oxidative stresses may contribute to the increased cancer risk characteristic of the hereditary nonpolyposis colorectal cancer syndrome.

Human prostate carcinoma tissues do not express the pi-class glutathione S-transferase (GST) and the regulatory genes near the GSTP1 gene, which encode the human pi-class GST, undergo hypermethylation during prostatic carcinogenesis. GSTP1 is expressed in prostatic cancer cell lines having GSTP1 alleles that contain hypomethylated promoter sequences. However, prostatic cancer cells with hypermethylated GSTP1 promoter sequences fail to express GSTP1 mRNA or polypeptides.

A cell-free system, after a sequential S phase/M phase synchronization uses extracts synthesized from mitotic chicken hepatoma cells, reveals the nuclear transformations arising during the active phase of apoptosis. It is indicated that in complete cells of human beings, mouse and chicken, lamina disassembly is an essential aspect of apoptosis. After the introduction of nuclei into the extracts, DNA is fragmented into nucleosomal ladder and the nuclear lamina disassembles.

The division of polychlorinated biphenyl congeners between particulate and dissolved phases of seawater along New Bedford Harbor, MA, was investigated using regression analysis. The results showed that the partitioning process was subject to seasonal trends. Around 70% of the variability in the log of the partition coefficients along the polychlorinated biphenyl gradient was due to temperature.

Exposure of DNA to strand breaking agents is associated with a transient increase in the level of wild-type p53 protein, resulting in cell cycle arrest at G1. Previous investigations have shown that the E6 protein encoded by the high-risk human papillomavirus genes interact with p53, leading to its degradation in vitro. Experiments conducted to determine the role of E6-p53 interactions in HPV infections showed that the viral protein could disrupt the normal cellular response to DNA damage through its interaction with p53. This may constitute an important step towards the accumulation of genetic changes associated with cervical tumorigenesis.