Emergent trends in the reported incidence of prostate cancer in Nigeria

Godwin O Ifere1, Fisseha Abebe2, Godwin A Ananaba1,31Department of Biological Sciences, 2Department of Mathematical Sciences, 3Center for Cancer Research and Therapeutic Development, Clark Atlanta University, Atlanta, GA, USABackground: To date there has not been any nationwide age-standardized incidence data reported for prostate cancer in Nigeria. We examined and integrated diverse trends in the age-specific incidence of prostate cancer into a comprehensive trend for Nigeria, and examined how best the existing data could generate a countrywide age-standardized incidence rate for the disease.Methods: Data were obtained from studies undertaken between 1970 and 2007 in referral hospital-based cancer registries. Records from at least one tertiary hospital in each of the six geopolitical zones of Nigeria were examined retrospectively. Data were also reported for the rural population in cross-sectional prospective studies. Age-standardized incidence rates and the annual incidence of disease were calculated.Results: Higher incidence rates for prostate cancer during this period were recorded for patients aged 60–69 years and 70–79 years, with a lower incidence rate for patients aged younger than 50 years. An exponential annual incidence rate of disease was observed in the 50–79 year age group and peaked at 70–79 years before dropping again at age 80 years. The results showed metastasis in more than half of these hospital-based prostate tumors.Conclusion: Our results suggest that prostate cancer occurs at a relatively young age in Nigerians and that hospital-based registry reports may not appropriately reflect the incidence of the disease in Nigeria. A countrywide screening program is urgently needed. Finally, the difference in reported stages of disease found in Nigerians and African-Americans versus Caucasians suggests biological differences in the prognosis. Nigeria may thus typify one of the ancestral populations that harbor inherited genes predisposing African-Americans to high-risk prostate cancer.Keywords: prostate cancer, annual age-standardized incidence rate, Nigeria cancer registr

Chemokine and Chemokine Receptor Dynamics during Genital Chlamydial Infection

Current design strategies for vaccines against certain microbial pathogens, including Chlamydia trachomatis, require the induction and targeting of specific immune effectors to the local sites of infection known as the mucosal effector sites. Chemokines and their receptors are important mediators of leukocyte trafficking and of the controlled recruitment of specific leukocyte clonotypes during host defense against infections and during inflammation. We analyzed the dynamics of chemokine and chemokine receptor expression in genital mucosae during genital chlamydial infection in a murine model to determine how these molecular entities influence the development of immunity and the clearance of infection. A time course study revealed an increase of up to threefold in the levels of expression of RANTES, monocyte chemotactic protein 1 (MCP-1), gamma-interferon-inducible protein 10 (IP-10), macrophage inflammatory protein 1α (MIP-1α), and intercellular adhesion molecule type 1 (ICAM-1) after genital infection with the C. trachomatis agent of mouse pneumonitis. Peak levels of expression of RANTES, MCP-1, and MIP-1α occurred by day 7 after primary infection, while those of IP-10 and ICAM-1 peaked by day 21. Expression levels of these molecules decreased by day 42 after primary infection, by which time all animals had resolved the infection, suggesting an infection-driven regulation of expression. A rapid upregulation of expression of these molecules was observed after secondary infection. The presence of cells bearing the chemokine receptors CCR5 and CXCR3, known to be preferentially expressed on Th1 and dendritic cells, was also synchronous with the kinetics of immune induction in the genital tract and clearance of infection. Results demonstrated that genital chlamydial infection is associated with a significant induction of chemokines and chemokine receptors that are involved in the recruitment of Th1 cells into the site of infection. Future studies will focus on how selective modulation of chemokines and their receptors can be used to optimize long-term immunity against Chlamydia

Host inflammatory response and development of complications of Chlamydia trachomatis genital infection in CCR5-deficient mice and subfertile women with the CCR5delta32 gene deletion

T cell immunity protects against diseases caused by the obligate intracellular bacterium Chlamydia trachomatis. Incidentally, host inflammatory response that includes T cells appears to also contribute to the pathogenesis of chlamydial diseases such as trachoma and tubal factor infertility (TFI). Therefore, designing effective prevention strategies requires a delineation of immune processes responsible for pathology and those mediating immunity, and identification of the immunogenetic factors predisposing to complication development. The chemokine receptor CCR5 is crucial for T cell activation and function since its deficiency causes suppression of T cell response. We investigated the hypothesis that the clearance of genital chlamydial infection in CCR5-deficient mice could be delayed in the short term; however, a beneficial effect could include protection against inflammation-related complications such as TFI. In a translational study in humans, we investigated the effect of a functional 32 bp deletion in the CCR5 gene on the risk of developing tubal pathology in Dutch Caucasian women with immunologic evidence [i.e., immunoglobulin G (IgG) responses] of chlamydial infection. When genitally-infected wild-type (WT) and CCR5 knockout (CCR5KO) mice were evaluated for microbiologic shedding of chlamydiae, there was a greater intensity of infection and delayed resolution in the knockout mice. However, compared to WT mice, the fertility of infected CCR5KO mice (measured by pregnancy rate) was only mildly affected in the short term and unaffected in the long term (70% vs 30% reduction in the short term, and 50 vs 0% in the long term, respectively). Immunobiologic analysis revealed that the diminished capacity of CCR5KO to control acute chlamydial infection correlated with the relatively low chemokine [interferon-inducible protein 10 (IP-10) and regulated upon activation normal cell expressed and secreted (RANTES)] and cytokine (mainly interferon-gamma and tumor necrosis factor-alpha) expression corresponding to a poor early T-helper I response. However, the reduced incidence of complications in the CCR5KO mice appears to correlate with the low activity of long term inflammatory mediators. Besides, the translational studies in humans revealed that among patients with positive anti-chlamydial IgG responses, tubal pathology correlated with a low incidence of CCR5delta32 deletion (7%), while women without tubal pathology had higher incidence of the CCR5delta32 deletion (31%) as compared to controls (19%). Thus, in mice and humans the inflammation associated with CCR5 function may predispose to development of complications of chlamydial infection, such as TFI