Association between cervical dysplasia and female genital schistosomiasis diagnosed by genital PCR in Zambian women.

BACKGROUND: Female genital schistosomiasis (FGS) is a neglected tropical gynaecological disease that affects millions of women in sub-Saharan Africa (SSA). FGS is caused by Schistosoma haematobium, a parasitic carcinogen involved in the pathogenesis of squamous cell carcinoma of the bladder. Cervical cancer incidence and mortality are highest in SSA, where pre-cancerous cervical dysplasia is often detected on screening with visual inspection with acetic acid (VIA). There are no studies evaluating the association between VIA positivity and FGS diagnosed by genital PCR. METHODS: Women were recruited from the Bilharzia and HIV (BILHIV) study in Zambia a community-based study comparing genital self-sampling to provider obtained cervicovaginal-lavage for the diagnosis of FGS in women aged 18-31. FGS was defined as positive Schistosoma DNA from any genital PCR. Urogenital schistosomiasis diagnostics included urine circulating anodic antigen, urine microscopy and portable colposcopy. Participants were offered cervical cancer screening using VIA at Livingstone Central Hospital. Associations of PCR confirmed FGS and other diagnostics with VIA positivity were assessed using multivariable logistic regression. RESULTS: VIA results were available from 237 BILHIV participants. A positive Schistosoma PCR in any genital specimen was detected in 14 women (5.9%), 28.6% (4/14) of these women had positive VIA compared to 9.0% without PCR evidence of schistosome infection (20/223). Schistosoma PCR positivity in any genital specimen was strongly associated with VIA positivity (OR: 6.08, 95% CI: 1.58-23.37, P = 0.02). CONCLUSIONS: This is the first study to find an association between FGS and positive VIA, a relationship that may be causal. Further longitudinal studies are needed.

Schistosoma mansoni-specific immune responses and allergy in Uganda.

Low allergy-related disease (ARD) prevalence in low-income countries may be partly attributed to helminth infections. In the Schistosoma mansoni (Sm)-endemic Lake Victoria islands (Uganda), we recently observed positive helminth-allergy associations, despite low ARD prevalence. To understand how Sm-induced cytokine and antibody profiles might influence allergic response profiles in this population, we assessed Schistosoma worm (SWA)- and egg antigen (SEA)-specific Th1 (IFN-γ), Th2 (IL-5, IL-13) and regulatory (IL-10) cytokine profiles (n = 407), and total (n = 471), SWA-, SEA- and allergen (house dust mite [HDM] and cockroach)-specific (as)IgE and IgG4 profiles (n = 2117) by ELISA. Wheeze was inversely associated with SWA-specific IFN-γ (P < .001) and IL-10 (P = .058), and SEA-specific IL-5 (P = .004). Conversely, having a detectable asIgE response was positively associated with SWA-specific IL-5 (P = .006) and IL-10 (P < .001). Total, SWA-, SEA- and allergen-specific IgE and IgG4 responses were higher among Sm Kato-Katz positive (SmKK+) and skin prick test (SPT)+ individuals compared to SmKK- and SPT- individuals. However, total and asIgG4/IgE ratios were lower among SPT+ and wheezing individuals. We conclude that, in this population, helminth-induced antibody and cytokine responses may underlie individual positive helminth-atopy associations, while the overall IgG4-IgE balance may contribute to the low overall prevalence of clinical allergies in such settings.

Further observations on the relationship between the FGFR4 Gly388Arg polymorphism and lung cancer prognosis.

The Gly388Arg polymorphism in the fibroblast growth factor receptor 4 (FGFR4) gene has been reported to influence prognosis in a wide variety of cancer types. To determine whether Gly388Arg is a marker for lung cancer prognosis, we genotyped 619 lung cancer patients with incident disease and examined the relationship between genotype and overall survival. While we employed a comprehensive set of statistical tests, including those sensitive to the detection of differences in early survival, our data provide little evidence to support the tenet that the FGFR4 Gly388Arg polymorphism is a clinically useful marker for lung cancer prognosis.

Prognostic significance of folate metabolism polymorphisms for lung cancer.

Functional nonsynonymous single-nucleotide polymorphisms (nsSNPs) of folate metabolism genes can influence the methylation of tumour suppressor genes, thereby potentially impacting on tumour behaviour. To investigate whether such polymorphisms influence lung cancer survival, we genotyped 14 nsSNPs mapping to methylene-tetrahydrofolate reductase (MTHFR), methionine synthase (MTR), methionine synthase reductase (MTRR); DNA methyltransferase (DNMT2), methylenetetrahydrofolate dehydrogenase (MTHFD1) and methenyltetrahydrofolate synthetase (MTHFS) in 619 Caucasian women with incident disease, 465 with non-small cell (NSCLC) and 154 with small cell lung cancer (SCLC). The most significant association detected was with MTHFS Thr202Ala, with carriers of variant alleles having a worse prognosis (hazard ratio (HR)=1.49; 95% confidence interval: 1.14-1.94). Associations were also detected between overall survival (OS) in SCLC and homozygosity for MTHFR 222Val (HR=1.92; 1.03-3.58) and between OS from NSCLC and MTRR 175Leu carrier status (HR=1.36; 1.06-1.75). While there is evidence that variation in the folate metabolism genes may influence prognosis from lung cancer, current data are insufficiently robust to distinguish individual patient outcome.

Case-control, kin-cohort and meta-analyses provide no support for STK15 F31I as a low penetrance colorectal cancer allele.

Recently, homozygosity for T91A single-nucleotide polymorphism (SNP) in the serine/threonine kinase (STK15) gene, which generates the substitution F31I has been proposed to increase the risk of a number of tumours including colorectal cancer (CRC). To further evaluate the relationship between STK15 F31I and risk of CRC, we genotyped 2558 CRC cases and 2680 controls for this polymorphism. We found no evidence that homozygosity for the STK15 31I genotype confers an increased risk of CRC (odds ratio=0.95, 95% confidence interval (CI): 0.74-1.24). We also conducted a kin-cohort analysis to assess risk among first-degree relatives of the CRC cases. The hazard ratio for I/I homozygotes compared to F/F homozygotes was 1.65 (95% CI: 0.39-3.17). A meta-analysis of our case-control data and three previous studies also provided no evidence of an elevated risk of CRC associated with homozygosity. These data provide no support for the hypothesis that sequence variation in STK15 defined by SNP F31I per se confers an elevated risk of CRC.