11 research outputs found

    Cycles climatiques et hydrothermalisme en Mer Rouge

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    Cette étude pluridisciplinaire couplant des approches de biostratigraphie, de sédimentologie et de géochimie isotopique et élémentaire a permis d'établir une relation entre les cycles climatiques et l'hydrothermalisme en mer Rouge. La mer Rouge est un jeune océan semi-fermé dans lequel l'activité hydrothermale se manifeste au sein de la zone axiale par la présence de fosses à saumure et/ou de sédiments minéralisés. Le caractère confiné de ce bassin, le rend extrêmement sensible aux variations océanographiques globales, en particulier celles liées à la cyclicité glaciaire et aux variations du niveau marin qui en résultent. L'étude porte sur cinq carottes prélevées au cours de la mission RedSed MD73 (1992) dans la partie centrale de la mer Rouge. Elles sont localisées du nord au sud dans la fosse Thétis, la fosse Valdivia, hors de l'axe, dans la fosse Suakin et dans la plaine Suakin. Le cadre chrono-stratigraphique des carottes a été défini à partir des données isotopiques de G. ruber couplé à des datations AMS 14C. Ces colonnes sédimentaires couvrent les derniers cycles climatiques du Quaternaire correspondant aux stades isotopiques 1 à 5. L'enregistrement haute résolution des variations de Globigerinoides ruber et de G. sacculifer à l'Holocène (un échantillon environ tous les 146 ans) a permis d'établir une nouvelle biozonation plus détaillée de cette période, qui est caractérisée par la succession de trois biozones. L'enregistrement des variations du carbone organique et de celles du soufre le long des carottes a permis d'identifier des niveaux de sapropèles aux stades 2 et 3, en plus de celui déjà répertorié au stade 1. La présence de ces sapropèles est un indice de sous-oxygénation des eaux de fond. L'enregistrement des métaux hydrothermaux (Fe, Mn, Zn) pendant les périodes climatiques prédéfinies, fait ressortir une abondance de ces métaux dans les sédiments de la plaine Suakin au Dernier Maximum Glaciaire (DMG) et au stade 3 et un appauvrissement en ces métaux des sédiments de la fosse Suakin au DMG, comme cela a déjà été observé dans la fosse Atlantis II. Le stade 1 est caractérisé dans les fosses Atlantis II, Thétis et Suakin par de fortes concentrations en métaux hydrothermaux dans les sédiments. L'évolution spatiale et temporelle des concentrations métallifères dans les sédiments, nous permet de proposer le mécanisme suivant qui rend compte de cette répartition : - En période d'oxygénation "normale" (stade 1), l'interface saumure-eau de mer assure une double fonction de barrière de densité et de barrière redox. Les métaux précipitent à cette interface et forment des niveaux hautement minéralisés dans les fosses, comme c'est le cas dans les fosses Atlantis II, Thétis et Suakin. - En période de sous-oxygénation des eaux de fond, cette interface saumure-eau de mer se réduit à une interface de densité et on assiste à la formation d'une nouvelle interface redox moins profonde. Les métaux des saumures diffusent vers l'eau de fond anoxique. Ils s'oxydent à la nouvelle interface redox, qui est plus étendue et se répandent hors fosse. Peu de métaux sédimentent pendant ces périodes dans les fosses. D'où la formation de sédiments enrichis en métaux hydrothermaux dans la plaine Suakin et de sédiments peu minéralisés dans les fosses Atlantis II et Suakin au DMG. Un bilan de matière, basé sur les résultats acquis dans la plaine Suakin a permis de placer le front redox au DMG à 1600 m de profondeur, avec une superficie de 5500 km2This multidisciplinary study yields approches, including biostratigraphy, sedimentology, elementary and isotopic geochemistry, allowed us to establish a relation between climatic events and hydrothermalism in the Red Sea. The Red Sea is a marginal basin, with bathymetric depressions located along the axis, filled with hot brines and/or metalliferous sediments owing to hydrothermal activity. This enclosed basin is extremely sensitive to global climate changes and sea level variations. This study is carried out on five cores collected in the central part of the Red Sea, during the RedSed MD73 cruise (1992). They have been taken from the north-to the south in the Thétis Deep, Valdivia Deep, outside the axis, in the Suakin Deep and Suakin plain. Time stratigraphic frameworks have been obtained for these cores on the basis of the oxygen isotope record based on single specimens of G. ruber, supported by AMS 14C results. They provide an uninterrupted record that covers isotopic stages 1 to 5. High-resolution records of planktonic foraminifera Globigerinoides ruber and G. sacculifer in the Holocene (one sample each 146 yrs) allow us to establish a new biostratigraphic assemblage characterized by three zonations in this climatic period. Down-core organic carbon and sulfur variations show sapropelic horizons in stages 2 (Last Glacial Maximum) and 3 together with the one already identified in stage 1. These sapropelic horizons indicate the occurrence of a low oxygen content of the deep waters during that time. Metalliferous sediments have been found in the Suakin plain during LGM and stage 3, whereas the Suakin Deep, sediments formed during the LGM, contained little metalliferous particles, as in the one of the Atlantis II Deep. Deposits of stage 1 in the Thétis, Suakin and Atlantis II Deep are very rich in metalliferous particules. Spatial and temporal variations of metalliferous concentrations in sediments allow us to suggest a mechanism of distribution of hydrothermal particles : - When deep waters are well oxygenated (stage 1), the brine/water interface plays the role of redox and density boundaries. Metalliferous particles precipitate at this interface. Thus, highly metalliferous deposits are formed in deeps, such as Suakin, Thétis and Atlantis II. - During periods of low oxygen content of deep waters, this brine water interface plays only the role of a density barrier, and a new shallow redox interface is formed. Metalliferous particles migrate to this new interface and spread over a large area. Sediments which are formed during these periods in the deeps, are poorly enriched in metals, such as in the Atlantis II and Suakin Deeps during LGM because of metal dispersion. Outside the deeps, sediments are enriched in metalliferous particles, like in the Suakin plain sediments. Balance calculation suggest that during LGM, the redox interface was located at 1600 m covering a surface of 5500 km2

    Evaluation de la Pollution Métallique des Sédiments Superficiels de la Lagune Potou en Période d’étiage (Littoral de la Côte d’Ivoire)

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    La présente étude vise à évaluer la pollution métallique des sédiments superficiels de la lagune Potou (littoral de la Côte d’Ivoire en période d’étiage). La méthode utilisée à cet effet repose en premier sur l’échantillonnage des sédiments et sur la détermination de leurs concentrations en ETM (Élément Trace Métallique) à l’aide de la technique spectrométrique. Ensuite, l’estimation du niveau de la pollution métallique des sédiments, a été faite en comparant les concentrations des métaux obtenues à celles de la croûte continentale de Wedepohl (1995) et à celles des sédiments non pollués de Calamari et Naeve (1994) et Kikouama et al. (2009). De même, l’estimation du niveau de la pollution métallique des sédiments a été réalisée par le calcul de plusieurs indices de pollution dont le facteur d’enrichissement et l’index de géo-accumulation. L’approche méthodologique s’est enfin achevée par l’évaluation des risques des sédiments en place à partir des valeurs guides TEC (Threshold Effects Concentrations) et PEC (Probable Effect Concentration) et par l’étude de la distribution spatiale des différents contaminants au sein de la zone étudiée. Au total, 15 ETM ont été identifiés dans les sédiments du milieu, à savoir l’aluminium (Al), l’arsenic (As), le calcium (Ca), le cadmium (Cd), le chrome (Cr), le cuivre (Cu), le fer (Fe), le potassium (K), le magnésium (Mg), le manganèse (Mn), le sodium (Na), le nickel (Ni), le plomb (Pb), l’antimoine (Sb), et le zinc (Zn). Ces ETM ont des teneurs variables évoluant en moyenne entre 0,81 et 46693,33mg/Kg. Cette importante variabilité est aussi constatée au niveau des valeurs d’enrichissement en ETM. Celles-ci sont comprises en moyenne entre 0,03 et 4,15mg/Kg. Concernant l’index de géo-accumulation, les valeurs trouvées sont en majorité négatives sauf chez le zinc (0,77mg/Kg) et l’antimoine (1,4 mg/Kg). L’ensemble de ces résultats a montré que les sédiments de la lagune Potou sont de mauvaise qualité car pollués par le cuivre, le fer, le zinc et l’antimoine. Ces métaux, en particulier le zinc et l’antimoine, peuvent exercer un effet néfaste sur les organismes aquatiques du milieu lagunaire ainsi que sur l’Homme. This paper focuses on evaluating the metallic pollution of the superficial sediments of the Potou lagoon (Coast of Côte d'Ivoire) during the low water period. The method used for this study is based, first of all, on the sampling of the sediments and on the determination of their respective concentrations in MTE (Metal Trace Element) using the spectrometric technique. The estimation of the level of metallic pollution of the sediments was made by comparing the concentrations of the metals obtained with those of the continental Wedepohl crust (1995) and those of the unpolluted sediments of Calamari and Naeve (1994) and Kikouama et al. (2009). It was also achieved by calculating several pollution indices including the enrichment factor and the geo-accumulation index. The methodological approach was finally completed by assessing the risks of sediments in place from the TEC (Threshold Effects Concentrations) and PEC (Probable Effect Concentration) guide values and by studying the spatial distribution of the various contaminants at the site within the study area. A total of 15 MTE were identified in the sediments of the medium, namely: aluminium (Al), arsenic (As), calcium (Ca), cadmium (Cd), chromium (Cr), copper (Cu), iron (Fe), potassium (K), magnesium (Mg), manganese (Mn), sodium (Na), nickel (Ni), lead (Pb), antimony (Sb), and zinc (Zn). These MTE have variable contents ranging on average between 0.81 and 46693.33 mg / kg. This important variability is also found in the MTE enrichment values. These are on average between 0.03 and 4.15. Regarding the geo-accumulation index, the values found are mostly negative except for zinc (0.77) and antimony (1.4). All of these results showed that the sediments of the Potou lagoon are of poor quality because they are polluted by copper, iron, zinc, and antimony. These metals, in particular zinc and antimony, can have a detrimental effect on the aquatic organisms that inhabit the environment as well as humans

    Genome-wide SNP analysis of Plasmodium falciparum shows differentiation at drug-resistance-associated loci among malaria transmission settings in southern Mali.

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    Plasmodium falciparum malaria cases in Africa represent over 90% of the global burden with Mali being amongst the 11 highest burden countries that account for 70% of this annual incidence. The persistence of P. falciparum despite massive global interventions is because of its genetic diversity that drives its ability to adapt to environmental changes, develop resistance to drugs, and evade the host immune system. Knowledge on P. falciparum genetic diversity across populations and intervention landscape is thus critical for the implementation of new strategies to eliminate malaria. This study assessed genetic variation with 12,177 high-quality SNPs from 830 Malian P. falciparum isolates collected between 2007 and 2017 from seven locations. The complexity of infections remained high, varied between sites, and showed a trend toward overall decreasing complexity over the decade. Though there was no significant substructure, allele frequencies varied geographically, partly driven by temporal variance in sampling, particularly for drug resistance and antigen loci. Thirty-two mutations in known drug resistance markers (pfcrt, pfdhps, pfdhfr, pfmdr1, pfmdr2, and pfk13) attained a frequency of at least 2% in the populations. SNPs within and around the major markers of resistance to quinolines (pfmdr1 and pfcrt) and antifolates (pfdhfr and pfdhps) varied temporally and geographically, with strong linkage disequilibrium and signatures of directional selection in the genome. These geo-temporal populations also differentiated at alleles in immune-related loci, including, protein E140, pfsurfin8, pfclag8, and pfceltos, as well as pftrap, which showed signatures of haplotype differentiation between populations. Several regions across the genomes, including five known drug resistance loci, showed signatures of differential positive selection. These results suggest that drugs and immune pressure are dominant selective forces against P. falciparum in Mali, but their effect on the parasite genome varies temporally and spatially. Interventions interacting with these genomic variants need to be routinely evaluated as malaria elimination strategies are implemented

    Different Plasmodium falciparum clearance times in two Malian villages following artesunate monotherapy.

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    BACKGROUND: Artemisinin resistance described as increased parasite clearance time (PCT) is rare in Africa. More sensitive methods such as qPCR might better characterize the clearance phenotype in sub-Saharan Africa. METHODS: PCT is explored in Mali using light microscopy and qPCR after artesunate for uncomplicated malaria. In two villages, patients were followed for 28 days. Blood smears and spots were collected respectively for microscopy and qPCR. Parasitemia slope half-life was calculated after microscopy. Patient residual parasitemia were measured by qPCR. RESULTS: Uncorrected adequate clinical and parasitological responses (ACPR) observed in Faladje and Bougoula-Hameau were 78% and 92%, respectively (p=0.01). This reached 100% for both after molecular correction. Proportions of 24H microscopy positive patients in Faladje and Bougoula-Hameau were 97.2% and 72%, respectively (p<0.0001). Slope half-life was 2.8h in Faladje vs 2H in Bougoula-Hameau (p<0.001) and Proportions of 72H patients with residual parasitemia were 68.5% and 40% in Faladje and Bougoula-Hameau, respectively (p=0.003). The mean residual parasitemia was 2.9 in Faladje vs. 0.008 in Bougoula-Hameau (p=0.002). Although artesunate is efficacious in Mali, the longer parasite clearance time with submicroscopic parasitemia observed may represent early signs of developing P. falciparum resistance to artemisinins

    Cycles climatiques et hydrothermalisme en mer Rouge

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    Cette étude pluridisciplinaire couplant des approches de biostratigraphie, de sédimentologie et de géochimie isotopique et élémentaire a permis d'établir une relation entre les cycles climatiques et l'hydrothermalisme en mer Rouge. La mer Rouge est un jeune océan semi-fermé dans lequel l'activité hydrothermale se manifeste au sein de la zone axiale par la présence de fosses à saumure et/ou de sédiments minéralisés. Le caractère confiné de ce bassin, le rend extrêmement sensible aux variations océanographiques globales, en particulier celles liées à la cyclicité glaciaire et aux variations du niveau marin qui en résultent. L'étude porte sur cinq carottes prélevées au cours de la mission RedSed MD73 (1992) dans la partie centrale de la mer Rouge. Elles sont localisées du nord au sud dans la fosse Thétis, la fosse Valdivia, hors de l'axe, dans la fosse Suakin et dans la plaine Suakin. Le cadre chrono-stratigraphique des carottes a été défini à partir des données isotopiques de G. ruber couplé à des datations AMS14C. Ces colonnes sédimentaires couvrent les derniers cycles climatiques du Quaternaire correspondant aux stades isotopiques 1 à 5. L'enregistrement haute résolution des variations de Globigerinoides ruber et de G. sacculifer à l'Holocène (un échantillon environ tous les 146 ans) a permis d'établir une nouvelle biozonation plus détaillée de cette période, qui est caractérisée par la succession de trois biozones. L'enregistrement des variations du carbone organique et de celles du soufre le long des carottes a permis d'identifier des niveaux de sapropèles aux stades 2 et 3, en plus de celui déjà répertorié au stade 1. La présence de ces sapropèles est un indice de sous-oxygénation des eaux de fond...BORDEAUX1-BU Sciences-Talence (335222101) / SudocSudocFranceF

    Clinical, Paraclinical, and Evolutionary Profiles of Kidney Failure in Gold Miners Hospitalized in a Nephrological Service in a Sub-Saharan African Country

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    Introduction. The purpose of this preliminary study is to describe the clinical, paraclinical, and evolutionary profiles of gold miner patients with kidney failure hospitalized in the nephrology and haemodialysis service in the Yalgado Ouédraogo University Hospital of Ouagadougou (CHU-YO). Patients and Methods. This was a longitudinal and descriptive study with a retrospective collection of data for the period from February 1, 2013, to March 31, 2018. Included were all gold miner patients who stayed and worked at an artisanal gold mining site for at least three months and who were diagnosed with acute or chronic kidney failure during hospitalization in the nephrology service. We collected sociodemographic, clinical, and paraclinical variables at admission and then three months later. Results. We included 50 patients; all were male and the average age was 29.4 ± 7.7 years. All patients were exposed to mercury and/or cyanide for an average of 4.5 ± 2.8 years. The average consultation/referral time for patients at the CHU-YO was 25.4 ± 14.9 days. The average of creatininemia was 2338.0 ± 791.4 μmol/L. Kidney failure was acute in five cases (10%) and chronic in the remaining 45 cases or 90%. Extrarenal purification was indicated in 43 cases (86%). It was not performed in nine of the 43 cases due to lack of financial resources for patients (six cases) or death prior to the onset of haemodialysis (three cases). Thirty-two of the 50 patients in the study (64% of cases) died. Conclusion. Chronic kidney failure in gold miners appears to be common and late-managed. A prospective study of kidney disease and its causes at gold mining sites and surrounding areas will assess the extent of the problem in the country and better clarify the prevention of these diseases in our country

    Enrichissement des sédiments de la lagune Ebrié (Côte d’Ivoire) en éléments traces métalliques (ETM) : influence sur la qualité des sédiments et les organismes benthiques

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    Problématique : Les travaux réalisés dans certaines baies de la lagune Ebrié (Côte d’Ivoire), ont montré une forte concentration des éléments traces métalliques (ETM) dans les sédiments en saison pluvieuse par rapport aux saisons sèche et de crue. Ces informations sont très importantes mais ne permettent pas de connaitre le niveau de concentration des ETM et la qualité de l’environnement lagunaire Ebrié en période pluvieuse ; car ces travaux se sont intéressés seulement à quelques baies au niveau d’Abidjan. Objectif : La présente étude pour combler ce déficit d’informations, se donne pour objectif de connaitre le niveau de pollution des sédiments de la lagune Ebrié en période pluvieuse par les éléments traces. Méthodologie et Résultats: Une campagne d’échantillonnage effectuée en juillet 2015, dans la lagune Ebrié, a permis de visiter 46 stations de prélèvement. Les sédiments ont été séchés et homogénéisés. Une quantité de 0,5 g de sédiments de taille inférieure à 63 µm a été digérée à chaud par un mélange d’eau régale et d’acide fluorhydrique. Le niveau d’enrichissement, de pollution et du risque toxique ont été calculé. Les teneurs moyennes sont de 55,20 µg/g pour le cobalt, 55,64 µg/g pour le nickel, 54,02 µg/g pour le cuivre, 132,33 µg/g pour le zinc, 0,75 µg/g pour le cadmium et de 118,88 µg/g pour le plomb. L’intensité de l’enrichissement des ETM se situe dans l’ensemble entre absence d’enrichissement et très fort enrichissement. Le cadmium est le plus enrichi. L’intensité de pollution des sédiments quant à elle se situe entre absence de pollution et fortement pollué. Le cuivre, le cadmium et le plomb constituent les polluants les plus importants. La qualité des sédiments expose les organismes benthiques à un risque toxique de 21 %, 49 % et de 76 %. Conclusion et application des résultats : Les sédiments de la lagune au niveau d’Abidjan sont les plus impactés par l’enrichissement en ETM. Ils présentent un risque pour les organismes benthiques. Le milieu lagunaire étant dynamique, ce risque toxique pourrait se propager et atteindre les zones éloignées. Les résultats de ces travaux permettent d’attirer l’attention des décideurs sur la qualité des sédiments qui arrivent dans la lagune Ebrié. Aussi, ils aident dans le choix des lieux d’installation des maquis, des restaurants et autres espaces de loisirs aux abords de la lagune Ebrié.Mots clés : ETM, enrichissement, qualité des sédiments, organismes benthiques, lagune Ebri

    Evidence of HIV-1 Genital Shedding after One Year of Antiretroviral Therapy in Females Recently Diagnosed in Bamako, Mali

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    Little is known about the dynamic of HIV-1 shedding and resistance profiles in the female genital reservoir after antiretroviral therapy (ART) initiation in resource-limited countries (RLCs), which is critical for evaluating the residual sexual HIV-1 transmission risk. The present study aimed to evaluate the efficacy of 1 year duration ART at blood and genital levels in females newly diagnosed for HIV-1 from three centers in Bamako, Mali. Seventy-eight consenting females were enrolled at the time of their HIV-1 infection diagnosis. HIV-1 RNA loads (Abbott Real-Time HIV-1 assay) were tested in blood and cervicovaginal fluids (CVF) before and 12 months after ART initiation. Primary and acquired resistances to ART were evaluated by ViroseqTM HIV-1 genotyping assay. The vaginal microbiota was analyzed using IonTorrentTM NGS technology (Thermo Fisher Scientific). Proportions of primary drug resistance mutations in blood and CVF were 13.4% and 25%, respectively. Discrepant profiles were observed in 25% of paired blood/CVF samples. The acquired resistance rate was 3.1% in blood. At month 12, undetectable HIV-1 RNA load was reached in 84.6% and 75% of blood and CVF samples, respectively. A vaginal dysbiosis was associated with HIV RNA shedding. Our findings emphasize the need of reinforcing education to improve retention in care system, as well as the necessity of regular virological monitoring before and during ART and of implementing vaginal dysbiosis diagnosis and treatment in RLCs

    Table1_Genome-wide SNP analysis of Plasmodium falciparum shows differentiation at drug-resistance-associated loci among malaria transmission settings in southern Mali

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    Plasmodium falciparum malaria cases in Africa represent over 90% of the global burden with Mali being amongst the 11 highest burden countries that account for 70% of this annual incidence. The persistence of P. falciparum despite massive global interventions is because of its genetic diversity that drives its ability to adapt to environmental changes, develop resistance to drugs, and evade the host immune system. Knowledge on P. falciparum genetic diversity across populations and intervention landscape is thus critical for the implementation of new strategies to eliminate malaria. This study assessed genetic variation with 12,177 high-quality SNPs from 830 Malian P. falciparum isolates collected between 2007 and 2017 from seven locations. The complexity of infections remained high, varied between sites, and showed a trend toward overall decreasing complexity over the decade. Though there was no significant substructure, allele frequencies varied geographically, partly driven by temporal variance in sampling, particularly for drug resistance and antigen loci. Thirty-two mutations in known drug resistance markers (pfcrt, pfdhps, pfdhfr, pfmdr1, pfmdr2, and pfk13) attained a frequency of at least 2% in the populations. SNPs within and around the major markers of resistance to quinolines (pfmdr1 and pfcrt) and antifolates (pfdhfr and pfdhps) varied temporally and geographically, with strong linkage disequilibrium and signatures of directional selection in the genome. These geo-temporal populations also differentiated at alleles in immune-related loci, including, protein E140, pfsurfin8, pfclag8, and pfceltos, as well as pftrap, which showed signatures of haplotype differentiation between populations. Several regions across the genomes, including five known drug resistance loci, showed signatures of differential positive selection. These results suggest that drugs and immune pressure are dominant selective forces against P. falciparum in Mali, but their effect on the parasite genome varies temporally and spatially. Interventions interacting with these genomic variants need to be routinely evaluated as malaria elimination strategies are implemented

    COX-2 gene promoter haplotypes and prostate cancer risk

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    Cyclooxygenase-2 (COX-2) is a key rate-limiting enzyme that converts arachidonic acid into pro-inflamatory prostaglandins. COX-2 expression is strongly correlated with increased tumor microvasculature density and plays an important role in inhibiting apoptosis, stimulating angiogenesis and promoting tumor cell metastasis and invasion. However, little is known about the role that sequence variation of the COX-2 gene contributes to prostate cancer. Thus, we searched for polymorphisms in the promoter region of the COX-2 gene using denaturing high-performance liquid chromatography. Four single nucleotide polymorphisms (SNPs), -1285A/G, -1265G/A, -899G/C and -297C/G, were detected and confirmed by direct sequencing. Three of the SNPs in the promoter region of COX-2 gene create at least three putative transcription factor binding sites and eliminate CCAAT/enhancer binding protein alpha (C/EBPα) and NF-κB binding sites. A case-control study of the four SNPs in African American (n=288), Bini Nigerian (n=264) and European American (n=184) prostate cancer cases and age-matched controls revealed that SNP -297G was associated with a decreased risk for prostate cancer [odds ratio (OR)=0.49; CI= 0.2-0.9; P=0.01]. The effect on risk was observed in both African Americans (OR=0.51; CI=0.2-0.9; P=0.01) and European Americans (OR=0.33; CI=0.1-0.9; P=0.02). In addition, SNPs -1265A and -899C were associated with increased prostate cancer risk in African Americans (OR=2.72; CI=1.3-5.8; P=0.007 and OR=3.67; CI= 1.4-9.9; P=0.007, respectively). Haplotype analyses revealed modest effects on susceptibility to prostate cancer across populations. Haplotype GGCC conferred increased risk in the African American and Nigerian populations. Conversely, haplotype AGGG exhibited a negative association with prostate cancer risk in African Americans (OR=0.4; CI= 0.1-0.9; P=0.02) and European Americans (OR=0.2; CI=0.1-0.9; P=0.03). These data suggest that variation of the COX-2 promoter may influence the risk and development of prostate cancer. © Oxford University Press 2004; all rights reserved
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