The Experts below are selected from a list of 180 Experts worldwide ranked by ideXlab platform
Hans Lilja - One of the best experts on this subject based on the ideXlab platform.
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a common prostate cancer risk variant 5 of msmb Microseminoprotein Beta is a strong predictor of circulating msp Microseminoprotein in multiple populations
Cancer Epidemiology Biomarkers & Prevention, 2010Co-Authors: Kevin M Waters, Robert J. Klein, Hans Lilja, Camilla Valtonenandre, Daniel O Stram, Loic Le Marchand, Mari T Peltola, Laurence N Kolonel, Brian E Henderson, Christopher A HaimanAbstract:Background: Beta-Microseminoprotein (MSP) is one of the three most abundantly secreted proteins of the prostate, and has been suggested as a biomarker for prostate cancer risk. A common variant, rs10993994, in the 5' region of the gene which encodes MSP (MSMB), has recently been identified as a risk factor for prostate cancer. Methods: We examined the association between rs10993994 genotype and MSP levels in a sample of 500 prostate cancer-free men from four racial/ethnic populations in the Multiethnic Cohort (European Americans, African Americans, Latinos, and Japanese Americans). Generalized linear models were used to estimate the association between rs10993994 genotype and MSP levels. Results: We observed robust associations between rs10994994 genotype and MSP levels in each racial/ethnic population (all P<10-8) with carriers of the C allele having lower geometric mean MSP levels (ng/mL) (CC/CT/TT genotypes: European Americans, 28.8/20.9/10.0; African Americans, 29.0/21.9/10.9; Latinos, 29.2/17.1/8.3; and Japanese Americans 25.8/16.4/6.7). We estimated the variant accounts for 30-50% of the variation in MSP levels in each population. We also observed significant differences in MSP levels between populations (P=3.5x10-6), with MSP levels observed to be highest in African Americans and lowest in Japanese Americans. Conclusions: Rs10993994 genotype is strongly associated with plasma MSP levels in multiple racial/ethnic populations. Impact: This supports the hypothesis that rs10993994 may be the biologically functional allele. Impact:
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a common prostate cancer risk variant 5 of Microseminoprotein Beta msmb is a strong predictor of circulating Beta Microseminoprotein msp levels in multiple populations
Cancer Epidemiology Biomarkers & Prevention, 2010Co-Authors: Kevin M Waters, Robert J. Klein, Hans Lilja, Camilla Valtonenandre, Daniel O Stram, Loic Le Marchand, Mari T Peltola, Laurence N Kolonel, Brian E Henderson, Christopher A HaimanAbstract:Background: Beta-Microseminoprotein (MSP) is one of the three most abundantly secreted proteins of the prostate and has been suggested as a biomarker for prostate cancer risk. A common variant, rs10993994, in the 5' region of the gene that encodes MSP (MSMB) has recently been identified as a risk factor for prostate cancer. Methods: We examined the association between rs10993994 genotype and MSP levels in a sample of 500 prostate cancer-free men from four racial/ethnic populations in the Multiethnic Cohort (European Americans, African Americans, Latinos, and Japanese Americans). Generalized linear models were used to estimate the association between rs10993994 genotype and MSP levels. Results: We observed robust associations between rs10994994 genotype and MSP levels in each racial/ethnic population (all P < 10(-8)), with carriers of the C allele having lower geometric mean MSP levels (ng/mL; CC/CT/TT genotypes: European Americans, 28.8/20.9/10.0; African Americans, 29.0/21.9/10.9; Latinos, 29.2/17.1/8.3; and Japanese Americans, 25.8/16.4/6.7). We estimated the variant accounts for 30% to 50% of the variation in MSP levels in each population. We also observed significant differences in MSP levels between populations (P = 3.5 x 10(-6)), with MSP levels observed to be highest in African Americans and lowest in Japanese Americans. Conclusions: Rs10993994 genotype is strongly associated with plasma MSP levels in multiple racial/ethnic populations. Impact: This supports the hypothesis that rs10993994 may be the biologically functional allele. Cancer Epidemiol Biomarkers Prev; 19(10); 2639-46. (C) 2010 AACR. (Less)
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polymorphisms at the Microseminoprotein Beta locus associated with physiologic variation in Beta Microseminoprotein and prostate specific antigen levels
Cancer Epidemiology Biomarkers & Prevention, 2010Co-Authors: Xing Xu, Hans Lilja, Christer Hallden, Camilla Valtonenandre, Charlotta Sävblom, Robert J. KleinAbstract:Background: rs10993994, a single nucleotide polymorphism (SNP) at the genetic locus encoding β-Microseminoprotein (β-MSP), is associated with both prostate cancer risk and levels of blood prostate-specific antigen (PSA), a biomarker used in prostate cancer screening. Therefore, we wished to determine the association between SNPs at MSMB , the gene encoding β-MSP, and the levels of prostate-produced biomarkers β-MSP, PSA, and human kallikrein 2 (hK2) in blood and semen. Methods: Blood and semen from 304 healthy young Swedish men (ages 18-21) were assayed for β-MSP, PSA, and hK2. SNPs around MSMB were genotyped from matched DNA and analyzed for quantitative association with biomarker levels. Empirical P values were multiple test–corrected and the independence of each SNP's effect was determined. Results: rs10993994 was significantly associated with the blood and semen levels of β-MSP (both P < 1.0 × 10−7) and PSA ( P = 0.00014 and P = 0.0019), and semen levels of hK2 ( P = 0.00027). Additional copies of the prostate cancer risk allele resulted in lower β-MSP but higher PSA levels, and singly explained 23% and 5% of the variation seen in semen β-MSP and PSA, respectively. Additional SNPs at MSMB are associated with β-MSP and PSA independently of rs10993994. Conclusions: SNPs at MSMB correlate with physiologic variation in β-MSP and PSA levels in the blood and semen of healthy young Swedish men. In particular, rs10993994 has a strong effect on β-MSP levels. Impact: Our results suggest a mechanism by which rs10993994 might predispose to prostate cancer and raise the possibility that genetic variation might need to be considered in interpreting the levels of these biomarkers. Cancer Epidemiol Biomarkers Prev; 19(8); 2035–42. ©2010 AACR. This article is featured in Highlights of This Issue, [p. 1887][1] [1]: /lookup/volpage/19/1887
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Beta Microseminoprotein in serum correlates with the levels in seminal plasma of young healthy males
Journal of Andrology, 2008Co-Authors: Camilla Valtonenandre, Hans Lilja, Per Fernlund, Charlotta Sävblom, Aleksander Giwercman, Ake LundwallAbstract:Beta-Microseminoprotein (MSP) is one of the most abundant proteins secreted by the prostate gland. Because MSP is also synthesized in nonreproductive organs, the establishment of a solid relationship between the levels of MSP in serum and semen is crucial for future studies connecting MSP with aging or diseases of the prostate gland. We developed a specific, competitive, europium-based immunoassay to measure MSP in serum and seminal plasma. We also produced recombinant MSP in insect cells using baculo virus and purified it to homogeneity by a novel approach with ethanol extraction and gel filtration. The median values of MSP in 205 young men were 12 mu g/L (2.5-97.5 percentile, 4.9-26 mu g/L) in serum and 0.53 g/L (2.5-97.5 percentile, 0.13-2.0 g/L) or 1.8 mg (2.5-97.5 percentile, 0.32-6.6 mg) in seminal plasma. MSP in serum showed significant correlation to MSP in seminal plasma (r =.50, P <.001). Significant correlations were also found in seminal plasma between MSP and prostate-specific antigen (PSA) (r =.65, P <.001) and between MSP and Zn2+ (r =.54, P <.001). The yield of recombinant MSP in culture medium was 35 mg/L or higher, and recovery following ethanol extraction was 80%-90%. MSP in serum reflects the prostate secretion of MSP, and correlations were also found in seminal plasma between MSP and PSA and Zn2+. This suggests that MSP in serum can be used as a marker of prostate secretion, despite the contribution from extra prostatic tissues. (Less)
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Beta‐Microseminoprotein in Serum Correlates With the Levels in Seminal Plasma of Young, Healthy Males
Journal of Andrology, 2008Co-Authors: Camilla Valtonen-andré, Hans Lilja, Per Fernlund, Charlotta Sävblom, Aleksander Giwercman, Ake LundwallAbstract:Beta-Microseminoprotein (MSP) is one of the most abundant proteins secreted by the prostate gland. Because MSP is also synthesized in nonreproductive organs, the establishment of a solid relationship between the levels of MSP in serum and semen is crucial for future studies connecting MSP with aging or diseases of the prostate gland. We developed a specific, competitive, europium-based immunoassay to measure MSP in serum and seminal plasma. We also produced recombinant MSP in insect cells using baculo virus and purified it to homogeneity by a novel approach with ethanol extraction and gel filtration. The median values of MSP in 205 young men were 12 mu g/L (2.5-97.5 percentile, 4.9-26 mu g/L) in serum and 0.53 g/L (2.5-97.5 percentile, 0.13-2.0 g/L) or 1.8 mg (2.5-97.5 percentile, 0.32-6.6 mg) in seminal plasma. MSP in serum showed significant correlation to MSP in seminal plasma (r =.50, P
Ake Lundwall - One of the best experts on this subject based on the ideXlab platform.
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Rapidly evolving marmoset MSMB genes are differently expressed in the male genital tract.
Reproductive Biology and Endocrinology, 2009Co-Authors: Ake Lundwall, P L Nayudu, Olivia Larne, Yvonne Ceder, Camilla Valtonen-andréAbstract:Background Beta-Microseminoprotein, an abundant component in prostatic fluid, is encoded by the potential tumor suppressor gene MSMB. Some New World monkeys carry several copies of this gene, in contrast to most mammals, including humans, which have one only. Here we have investigated the background for the species difference by analyzing the chromosomal organization and expression of MSMB in the common marmoset (Callithrix jacchus).
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Rapidly evolving marmoset MSMB genes are differently expressed in the male genital tract
Reproductive Biology and Endocrinology, 2009Co-Authors: Ake Lundwall, Olivia Larne, Yvonne Ceder, Penelope L Nayudu, Camilla Valtonen-andréAbstract:Background Beta-Microseminoprotein, an abundant component in prostatic fluid, is encoded by the potential tumor suppressor gene MSMB. Some New World monkeys carry several copies of this gene, in contrast to most mammals, including humans, which have one only. Here we have investigated the background for the species difference by analyzing the chromosomal organization and expression of MSMB in the common marmoset (Callithrix jacchus). Methods Genes were identified in the Callithrix jacchus genome database using bioinformatics and transcripts were analyzed by RT-PCR and quantified by real time PCR in the presence of SYBR green. Results The common marmoset has five MSMB: one processed pseudogene and four functional genes. The latter encompass homologous genomic regions of 32-35 kb, containing the genes of 12-14 kb and conserved upstream and downstream regions of 14-19 kb and 3-4 kb. One gene, MSMB1, occupies the same position on the chromosome as the single human gene. On the same chromosome, but several Mb away, is another MSMB locus situated with MSMB2, MSMB3 and MSMB4 arranged in tandem. Measurements of transcripts demonstrated that all functional genes are expressed in the male genital tract, generating very high transcript levels in the prostate. The transcript levels in seminal vesicles and testis are two and four orders of magnitude lower. A single gene, MSMB3, accounts for more than 90% of MSMB transcripts in both the prostate and the seminal vesicles, whereas in the testis around half of the transcripts originate from MSMB2. These genes display rapid evolution with a skewed distribution of mutated nucleotides; in MSMB2 they affect nucleotides encoding the N-terminal Greek key domain, whereas in MSMB3 it is the C-terminal MSMB-unique domain that is affected. Conclusion Callitrichide monkeys have four functional MSMB that are all expressed in the male genital tract, but the product from one gene, MSMB3, will predominate in seminal plasma. This gene and MSMB2, the predominating testicular gene, have accumulated mutations that affect different parts of the translation products, suggesting an ongoing molecular specialization that presumably yields functional differences in accessory sex glands and testis.
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Beta Microseminoprotein in serum correlates with the levels in seminal plasma of young healthy males
Journal of Andrology, 2008Co-Authors: Camilla Valtonenandre, Hans Lilja, Per Fernlund, Charlotta Sävblom, Aleksander Giwercman, Ake LundwallAbstract:Beta-Microseminoprotein (MSP) is one of the most abundant proteins secreted by the prostate gland. Because MSP is also synthesized in nonreproductive organs, the establishment of a solid relationship between the levels of MSP in serum and semen is crucial for future studies connecting MSP with aging or diseases of the prostate gland. We developed a specific, competitive, europium-based immunoassay to measure MSP in serum and seminal plasma. We also produced recombinant MSP in insect cells using baculo virus and purified it to homogeneity by a novel approach with ethanol extraction and gel filtration. The median values of MSP in 205 young men were 12 mu g/L (2.5-97.5 percentile, 4.9-26 mu g/L) in serum and 0.53 g/L (2.5-97.5 percentile, 0.13-2.0 g/L) or 1.8 mg (2.5-97.5 percentile, 0.32-6.6 mg) in seminal plasma. MSP in serum showed significant correlation to MSP in seminal plasma (r =.50, P <.001). Significant correlations were also found in seminal plasma between MSP and prostate-specific antigen (PSA) (r =.65, P <.001) and between MSP and Zn2+ (r =.54, P <.001). The yield of recombinant MSP in culture medium was 35 mg/L or higher, and recovery following ethanol extraction was 80%-90%. MSP in serum reflects the prostate secretion of MSP, and correlations were also found in seminal plasma between MSP and PSA and Zn2+. This suggests that MSP in serum can be used as a marker of prostate secretion, despite the contribution from extra prostatic tissues. (Less)
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Beta‐Microseminoprotein in Serum Correlates With the Levels in Seminal Plasma of Young, Healthy Males
Journal of Andrology, 2008Co-Authors: Camilla Valtonen-andré, Hans Lilja, Per Fernlund, Charlotta Sävblom, Aleksander Giwercman, Ake LundwallAbstract:Beta-Microseminoprotein (MSP) is one of the most abundant proteins secreted by the prostate gland. Because MSP is also synthesized in nonreproductive organs, the establishment of a solid relationship between the levels of MSP in serum and semen is crucial for future studies connecting MSP with aging or diseases of the prostate gland. We developed a specific, competitive, europium-based immunoassay to measure MSP in serum and seminal plasma. We also produced recombinant MSP in insect cells using baculo virus and purified it to homogeneity by a novel approach with ethanol extraction and gel filtration. The median values of MSP in 205 young men were 12 mu g/L (2.5-97.5 percentile, 4.9-26 mu g/L) in serum and 0.53 g/L (2.5-97.5 percentile, 0.13-2.0 g/L) or 1.8 mg (2.5-97.5 percentile, 0.32-6.6 mg) in seminal plasma. MSP in serum showed significant correlation to MSP in seminal plasma (r =.50, P
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the cotton top tamarin saguinus oedipus has five Beta Microseminoprotein genes two of which are pseudogenes
DNA and Cell Biology, 2008Co-Authors: Camilla Valtonenandre, Ake LundwallAbstract:Beta-Microseminoprotein (MSP) is one of the most abundant proteins in human seminal plasma and is secreted from the prostate gland. Its evolution can be traced from primates down to nonvertebrate species such as amphioxus, despite substantial differences in the primary structure. Most mammals are known to have one single MSP gene, but we have previously shown that the cotton-top tamarin and the common marmoset-two New World monkeys-carry several MSP genes. In this study we continue our characterization of MSP genes in the cotton-top tamarin by presenting the full nucleotide sequence of the three previously identified genes, mspA, mspE, and mspJ. A promoter analysis using luciferase reporter showed that mspE is as transcriptionally active as the single human MSP gene, whereas mspA and mspJ display no activity with this assay. Two novel MSP genes were also identified, mspB and mspH, both of which are pseudogenes. MspB has a frameshift mutation in the third exon resulting in a new C-terminus and premature stop of translation. MspH has the features of a processed pseudogene, originating from a transcript of mspE. It is integrated into the genome together with another processed pseudogene originating from a transcript of the nucleoporin gene NUP88. The MSP genes described in this study probably arose by phylogenetically rather late duplication or retrotransposition, suggesting that they are confined to a limited number of New World monkeys.
Camilla Valtonenandre - One of the best experts on this subject based on the ideXlab platform.
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levels of Beta Microseminoprotein in blood and risk of prostate cancer in multiple populations
Journal of the National Cancer Institute, 2013Co-Authors: Christopher A Haiman, Camilla Valtonenandre, Kevin M Waters, Daniel O Stram, Mari T Peltola, Andrew J Vickers, Lynne R Wilkens, Katharina Braun, Kim Pettersson, Loic Le MarchandAbstract:Although prostate cancer is the most common cancer among men in the United States, risk factors for the disease remain largely unknown. More than 40 common low-risk genetic variants have been discovered through genome-wide association studies of prostate cancer (1–6). One such variant is a single nucleotide polymorphism (rs10993994) in the 5’ region of the Microseminoprotein-β (MSMB) gene, which encodes for β-Microseminoprotein (MSP) (2,6). The risk allele (T nucleotide) for prostate cancer has been shown to be strongly associated with lower circulating MSP levels in multiple populations, with the variant accounting for as much as 50% of the variation in MSP levels in blood or seminal fluid (7,8). MSP is one of the most highly secreted proteins from the prostate, and circulating levels have been shown to be positively correlated (r = approximately 0.2) with both levels of total and free prostate-specific antigen (PSA) (8). In contrast with PSA, whereby risk of prostate cancer increases with higher PSA levels, MSP levels measured in serum, urine, and prostate tissue have been shown to be statistically significantly lower in men with prostate cancer and even lower in men with aggressive disease (9,10). The reproducible association of rs10993994 with prostate cancer risk and circulating MSP levels implicates MSP in the etiology of prostate cancer (11). However, a prospective study has yet to examine MSP levels as a risk factor for incident prostate cancer and as a potentially clinically informative marker for early detection. To determine the prospective relationship between circulating prediagnostic levels of MSP and prostate cancer risk, we measured MSP and PSA in a nested, multiethnic, case–control study of prostate cancer among men in the Multiethnic Cohort.
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a common prostate cancer risk variant 5 of Microseminoprotein Beta msmb is a strong predictor of circulating Beta Microseminoprotein msp levels in multiple populations
Cancer Epidemiology Biomarkers & Prevention, 2010Co-Authors: Kevin M Waters, Robert J. Klein, Hans Lilja, Camilla Valtonenandre, Daniel O Stram, Loic Le Marchand, Mari T Peltola, Laurence N Kolonel, Brian E Henderson, Christopher A HaimanAbstract:Background: Beta-Microseminoprotein (MSP) is one of the three most abundantly secreted proteins of the prostate and has been suggested as a biomarker for prostate cancer risk. A common variant, rs10993994, in the 5' region of the gene that encodes MSP (MSMB) has recently been identified as a risk factor for prostate cancer. Methods: We examined the association between rs10993994 genotype and MSP levels in a sample of 500 prostate cancer-free men from four racial/ethnic populations in the Multiethnic Cohort (European Americans, African Americans, Latinos, and Japanese Americans). Generalized linear models were used to estimate the association between rs10993994 genotype and MSP levels. Results: We observed robust associations between rs10994994 genotype and MSP levels in each racial/ethnic population (all P < 10(-8)), with carriers of the C allele having lower geometric mean MSP levels (ng/mL; CC/CT/TT genotypes: European Americans, 28.8/20.9/10.0; African Americans, 29.0/21.9/10.9; Latinos, 29.2/17.1/8.3; and Japanese Americans, 25.8/16.4/6.7). We estimated the variant accounts for 30% to 50% of the variation in MSP levels in each population. We also observed significant differences in MSP levels between populations (P = 3.5 x 10(-6)), with MSP levels observed to be highest in African Americans and lowest in Japanese Americans. Conclusions: Rs10993994 genotype is strongly associated with plasma MSP levels in multiple racial/ethnic populations. Impact: This supports the hypothesis that rs10993994 may be the biologically functional allele. Cancer Epidemiol Biomarkers Prev; 19(10); 2639-46. (C) 2010 AACR. (Less)
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a common prostate cancer risk variant 5 of msmb Microseminoprotein Beta is a strong predictor of circulating msp Microseminoprotein in multiple populations
Cancer Epidemiology Biomarkers & Prevention, 2010Co-Authors: Kevin M Waters, Robert J. Klein, Hans Lilja, Camilla Valtonenandre, Daniel O Stram, Loic Le Marchand, Mari T Peltola, Laurence N Kolonel, Brian E Henderson, Christopher A HaimanAbstract:Background: Beta-Microseminoprotein (MSP) is one of the three most abundantly secreted proteins of the prostate, and has been suggested as a biomarker for prostate cancer risk. A common variant, rs10993994, in the 5' region of the gene which encodes MSP (MSMB), has recently been identified as a risk factor for prostate cancer. Methods: We examined the association between rs10993994 genotype and MSP levels in a sample of 500 prostate cancer-free men from four racial/ethnic populations in the Multiethnic Cohort (European Americans, African Americans, Latinos, and Japanese Americans). Generalized linear models were used to estimate the association between rs10993994 genotype and MSP levels. Results: We observed robust associations between rs10994994 genotype and MSP levels in each racial/ethnic population (all P<10-8) with carriers of the C allele having lower geometric mean MSP levels (ng/mL) (CC/CT/TT genotypes: European Americans, 28.8/20.9/10.0; African Americans, 29.0/21.9/10.9; Latinos, 29.2/17.1/8.3; and Japanese Americans 25.8/16.4/6.7). We estimated the variant accounts for 30-50% of the variation in MSP levels in each population. We also observed significant differences in MSP levels between populations (P=3.5x10-6), with MSP levels observed to be highest in African Americans and lowest in Japanese Americans. Conclusions: Rs10993994 genotype is strongly associated with plasma MSP levels in multiple racial/ethnic populations. Impact: This supports the hypothesis that rs10993994 may be the biologically functional allele. Impact:
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polymorphisms at the Microseminoprotein Beta locus associated with physiologic variation in Beta Microseminoprotein and prostate specific antigen levels
Cancer Epidemiology Biomarkers & Prevention, 2010Co-Authors: Xing Xu, Hans Lilja, Christer Hallden, Camilla Valtonenandre, Charlotta Sävblom, Robert J. KleinAbstract:Background: rs10993994, a single nucleotide polymorphism (SNP) at the genetic locus encoding β-Microseminoprotein (β-MSP), is associated with both prostate cancer risk and levels of blood prostate-specific antigen (PSA), a biomarker used in prostate cancer screening. Therefore, we wished to determine the association between SNPs at MSMB , the gene encoding β-MSP, and the levels of prostate-produced biomarkers β-MSP, PSA, and human kallikrein 2 (hK2) in blood and semen. Methods: Blood and semen from 304 healthy young Swedish men (ages 18-21) were assayed for β-MSP, PSA, and hK2. SNPs around MSMB were genotyped from matched DNA and analyzed for quantitative association with biomarker levels. Empirical P values were multiple test–corrected and the independence of each SNP's effect was determined. Results: rs10993994 was significantly associated with the blood and semen levels of β-MSP (both P < 1.0 × 10−7) and PSA ( P = 0.00014 and P = 0.0019), and semen levels of hK2 ( P = 0.00027). Additional copies of the prostate cancer risk allele resulted in lower β-MSP but higher PSA levels, and singly explained 23% and 5% of the variation seen in semen β-MSP and PSA, respectively. Additional SNPs at MSMB are associated with β-MSP and PSA independently of rs10993994. Conclusions: SNPs at MSMB correlate with physiologic variation in β-MSP and PSA levels in the blood and semen of healthy young Swedish men. In particular, rs10993994 has a strong effect on β-MSP levels. Impact: Our results suggest a mechanism by which rs10993994 might predispose to prostate cancer and raise the possibility that genetic variation might need to be considered in interpreting the levels of these biomarkers. Cancer Epidemiol Biomarkers Prev; 19(8); 2035–42. ©2010 AACR. This article is featured in Highlights of This Issue, [p. 1887][1] [1]: /lookup/volpage/19/1887
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Beta Microseminoprotein in serum correlates with the levels in seminal plasma of young healthy males
Journal of Andrology, 2008Co-Authors: Camilla Valtonenandre, Hans Lilja, Per Fernlund, Charlotta Sävblom, Aleksander Giwercman, Ake LundwallAbstract:Beta-Microseminoprotein (MSP) is one of the most abundant proteins secreted by the prostate gland. Because MSP is also synthesized in nonreproductive organs, the establishment of a solid relationship between the levels of MSP in serum and semen is crucial for future studies connecting MSP with aging or diseases of the prostate gland. We developed a specific, competitive, europium-based immunoassay to measure MSP in serum and seminal plasma. We also produced recombinant MSP in insect cells using baculo virus and purified it to homogeneity by a novel approach with ethanol extraction and gel filtration. The median values of MSP in 205 young men were 12 mu g/L (2.5-97.5 percentile, 4.9-26 mu g/L) in serum and 0.53 g/L (2.5-97.5 percentile, 0.13-2.0 g/L) or 1.8 mg (2.5-97.5 percentile, 0.32-6.6 mg) in seminal plasma. MSP in serum showed significant correlation to MSP in seminal plasma (r =.50, P <.001). Significant correlations were also found in seminal plasma between MSP and prostate-specific antigen (PSA) (r =.65, P <.001) and between MSP and Zn2+ (r =.54, P <.001). The yield of recombinant MSP in culture medium was 35 mg/L or higher, and recovery following ethanol extraction was 80%-90%. MSP in serum reflects the prostate secretion of MSP, and correlations were also found in seminal plasma between MSP and PSA and Zn2+. This suggests that MSP in serum can be used as a marker of prostate secretion, despite the contribution from extra prostatic tissues. (Less)
Per Fernlund - One of the best experts on this subject based on the ideXlab platform.
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Hyperplasia of gastric antral β-Microseminoprotein endocrine-like cells and increased serum levels of β-Microseminoprotein in atrophic corpus gastritis
Scandinavian Journal of Gastroenterology, 2009Co-Authors: Hakan Weiber, Kurt Borch, Clas Lindström, E. Toth, Per FernlundAbstract:BACKGROUND: Beta-Microseminoprotein is a 94-kDa protein present on most mucosal surfaces in the body. It is produced in mucin cells but is also found in a particular type of cells (E-cells) in the gastric antral mucosa. Most of these cells also contain gastrin. In atrophic corpus gastritis the gastrin-producing cells become hyperplastic, and the patients have hypergastrinemia. We wanted to ascertain whether there is a similar effect on the E-cells and on the concentration of Beta-Microseminoprotein in serum. METHODS: Antral biopsy specimens from 10 patients with atrophic corpus gastritis and 10 controls were stained immunohistochemically for Beta-Microseminoprotein and gastrin. Beta-Microseminoprotein and gastrin were measured by radioimmunoassay in serum from 15 women with atrophic corpus gastritis and 31 healthy female blood donors. RESULTS: There was a 3.5-fold increase of the number of E-cells (which also were hypertrophic) and a 2.1 times higher serum concentration of Beta-Microseminoprotein in the patients with atrophic corpus gastritis than in the control subjects. Gastrin was seen in 28% of the E-cells in patients with atrophic corpus gastritis, compared with 87% in normal antral mucosa. There was no correlation between the serum concentrations of Beta-Microseminoprotein and gastrin. CONCLUSIONS: In atrophic corpus gastritis antrum E-cells undergo hyperplasia and hypertrophy, and the proportion of E-cells containing gastrin decreases. Increased amounts of Beta-Microseminoprotein are secreted to the blood but uncorrelated with gastrin.
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Cysteine-rich secretory proteins in snake venoms form high affinity complexes with human and porcine Beta-Microseminoproteins.
Toxicon, 2009Co-Authors: Karin M Hansson, Margareta Kjellberg, Per FernlundAbstract:Beta-Microseminoprotein (MSP), a 10kDa protein in human seminal plasma, binds human cysteine-rich secretory protein-3 (CRISP-3) with high affinity. CRISP-3 is a member of the family of CRISPs, which are widespread among animals. In this work we show that human as well as porcine MSP binds catrin, latisemin, pseudecin, and triflin, which are CRISPs present in the venoms of the snakes Crotalus atrox, Laticauda semifasciata, Pseudechis porphyriacus, and Trimeresurus flavoviridis, respectively. The CRISPs were purified from the venoms by affinity chromatography on a human MSP column and their identities were settled by gel electrophoresis and mass spectrometry. Their interactions with human and porcine MSPs were studied with size exclusion chromatography and surface plasmon resonance measurements. The binding affinities at 25 degrees C were between 10(-10)M and 10(-7)M for most of the interactions, with higher affinities for the interactions with porcine MSP compared to human MSP and with Elapidae CRISPs compared to Viperidae CRISPs. The high affinities of the bindings in spite of the differences in amino acid sequence between the MSPs as well as between the CRISPs indicate that the binding is tolerant to amino acid sequence variation and raise the question how universal this cross-species reaction between MSPs and CRISPs is.
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a model of the complex between human Beta Microseminoprotein and crisp 3 based on nmr data
Biochemical and Biophysical Research Communications, 2009Co-Authors: Houman Ghasriani, Per Fernlund, Lene Udby, Torbjorn DrakenbergAbstract:Beta-Microseminoprotein (MSP), a 10kDa seminal plasma protein, forms a tight complex with cysteine-rich secretory protein 3 (CRISP-3) from granulocytes. The 3D structure of human MSP has been determined but there is as yet no 3D structure for CRISP-3. We have now studied the complex between human MSP and CRISP-3 with multidimensional NMR. (15)N-HSQC spectra show substantial differences between free and complexed hMSP. Using several 3D-NMR spectra of triply labeled hMSP in complex with a recombinant N-terminal domain of CRISP-3, most of the backbone of hMSP could be assigned. The data show that only one side of hMSP, comprising Beta-strands 1, 4, 5, and 8 are affected by the complex formation, indicating that Beta-strands 1 and 8 form the main binding surface. Based on this we present a tentative structure for the hMSP-CRISP-3 complex using the known crystal structure of triflin as a model of CRISP-3.
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Beta Microseminoprotein in serum correlates with the levels in seminal plasma of young healthy males
Journal of Andrology, 2008Co-Authors: Camilla Valtonenandre, Hans Lilja, Per Fernlund, Charlotta Sävblom, Aleksander Giwercman, Ake LundwallAbstract:Beta-Microseminoprotein (MSP) is one of the most abundant proteins secreted by the prostate gland. Because MSP is also synthesized in nonreproductive organs, the establishment of a solid relationship between the levels of MSP in serum and semen is crucial for future studies connecting MSP with aging or diseases of the prostate gland. We developed a specific, competitive, europium-based immunoassay to measure MSP in serum and seminal plasma. We also produced recombinant MSP in insect cells using baculo virus and purified it to homogeneity by a novel approach with ethanol extraction and gel filtration. The median values of MSP in 205 young men were 12 mu g/L (2.5-97.5 percentile, 4.9-26 mu g/L) in serum and 0.53 g/L (2.5-97.5 percentile, 0.13-2.0 g/L) or 1.8 mg (2.5-97.5 percentile, 0.32-6.6 mg) in seminal plasma. MSP in serum showed significant correlation to MSP in seminal plasma (r =.50, P <.001). Significant correlations were also found in seminal plasma between MSP and prostate-specific antigen (PSA) (r =.65, P <.001) and between MSP and Zn2+ (r =.54, P <.001). The yield of recombinant MSP in culture medium was 35 mg/L or higher, and recovery following ethanol extraction was 80%-90%. MSP in serum reflects the prostate secretion of MSP, and correlations were also found in seminal plasma between MSP and PSA and Zn2+. This suggests that MSP in serum can be used as a marker of prostate secretion, despite the contribution from extra prostatic tissues. (Less)
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Beta‐Microseminoprotein in Serum Correlates With the Levels in Seminal Plasma of Young, Healthy Males
Journal of Andrology, 2008Co-Authors: Camilla Valtonen-andré, Hans Lilja, Per Fernlund, Charlotta Sävblom, Aleksander Giwercman, Ake LundwallAbstract:Beta-Microseminoprotein (MSP) is one of the most abundant proteins secreted by the prostate gland. Because MSP is also synthesized in nonreproductive organs, the establishment of a solid relationship between the levels of MSP in serum and semen is crucial for future studies connecting MSP with aging or diseases of the prostate gland. We developed a specific, competitive, europium-based immunoassay to measure MSP in serum and seminal plasma. We also produced recombinant MSP in insect cells using baculo virus and purified it to homogeneity by a novel approach with ethanol extraction and gel filtration. The median values of MSP in 205 young men were 12 mu g/L (2.5-97.5 percentile, 4.9-26 mu g/L) in serum and 0.53 g/L (2.5-97.5 percentile, 0.13-2.0 g/L) or 1.8 mg (2.5-97.5 percentile, 0.32-6.6 mg) in seminal plasma. MSP in serum showed significant correlation to MSP in seminal plasma (r =.50, P
Robert J. Klein - One of the best experts on this subject based on the ideXlab platform.
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a common prostate cancer risk variant 5 of Microseminoprotein Beta msmb is a strong predictor of circulating Beta Microseminoprotein msp levels in multiple populations
Cancer Epidemiology Biomarkers & Prevention, 2010Co-Authors: Kevin M Waters, Robert J. Klein, Hans Lilja, Camilla Valtonenandre, Daniel O Stram, Loic Le Marchand, Mari T Peltola, Laurence N Kolonel, Brian E Henderson, Christopher A HaimanAbstract:Background: Beta-Microseminoprotein (MSP) is one of the three most abundantly secreted proteins of the prostate and has been suggested as a biomarker for prostate cancer risk. A common variant, rs10993994, in the 5' region of the gene that encodes MSP (MSMB) has recently been identified as a risk factor for prostate cancer. Methods: We examined the association between rs10993994 genotype and MSP levels in a sample of 500 prostate cancer-free men from four racial/ethnic populations in the Multiethnic Cohort (European Americans, African Americans, Latinos, and Japanese Americans). Generalized linear models were used to estimate the association between rs10993994 genotype and MSP levels. Results: We observed robust associations between rs10994994 genotype and MSP levels in each racial/ethnic population (all P < 10(-8)), with carriers of the C allele having lower geometric mean MSP levels (ng/mL; CC/CT/TT genotypes: European Americans, 28.8/20.9/10.0; African Americans, 29.0/21.9/10.9; Latinos, 29.2/17.1/8.3; and Japanese Americans, 25.8/16.4/6.7). We estimated the variant accounts for 30% to 50% of the variation in MSP levels in each population. We also observed significant differences in MSP levels between populations (P = 3.5 x 10(-6)), with MSP levels observed to be highest in African Americans and lowest in Japanese Americans. Conclusions: Rs10993994 genotype is strongly associated with plasma MSP levels in multiple racial/ethnic populations. Impact: This supports the hypothesis that rs10993994 may be the biologically functional allele. Cancer Epidemiol Biomarkers Prev; 19(10); 2639-46. (C) 2010 AACR. (Less)
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a common prostate cancer risk variant 5 of msmb Microseminoprotein Beta is a strong predictor of circulating msp Microseminoprotein in multiple populations
Cancer Epidemiology Biomarkers & Prevention, 2010Co-Authors: Kevin M Waters, Robert J. Klein, Hans Lilja, Camilla Valtonenandre, Daniel O Stram, Loic Le Marchand, Mari T Peltola, Laurence N Kolonel, Brian E Henderson, Christopher A HaimanAbstract:Background: Beta-Microseminoprotein (MSP) is one of the three most abundantly secreted proteins of the prostate, and has been suggested as a biomarker for prostate cancer risk. A common variant, rs10993994, in the 5' region of the gene which encodes MSP (MSMB), has recently been identified as a risk factor for prostate cancer. Methods: We examined the association between rs10993994 genotype and MSP levels in a sample of 500 prostate cancer-free men from four racial/ethnic populations in the Multiethnic Cohort (European Americans, African Americans, Latinos, and Japanese Americans). Generalized linear models were used to estimate the association between rs10993994 genotype and MSP levels. Results: We observed robust associations between rs10994994 genotype and MSP levels in each racial/ethnic population (all P<10-8) with carriers of the C allele having lower geometric mean MSP levels (ng/mL) (CC/CT/TT genotypes: European Americans, 28.8/20.9/10.0; African Americans, 29.0/21.9/10.9; Latinos, 29.2/17.1/8.3; and Japanese Americans 25.8/16.4/6.7). We estimated the variant accounts for 30-50% of the variation in MSP levels in each population. We also observed significant differences in MSP levels between populations (P=3.5x10-6), with MSP levels observed to be highest in African Americans and lowest in Japanese Americans. Conclusions: Rs10993994 genotype is strongly associated with plasma MSP levels in multiple racial/ethnic populations. Impact: This supports the hypothesis that rs10993994 may be the biologically functional allele. Impact:
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polymorphisms at the Microseminoprotein Beta locus associated with physiologic variation in Beta Microseminoprotein and prostate specific antigen levels
Cancer Epidemiology Biomarkers & Prevention, 2010Co-Authors: Xing Xu, Hans Lilja, Christer Hallden, Camilla Valtonenandre, Charlotta Sävblom, Robert J. KleinAbstract:Background: rs10993994, a single nucleotide polymorphism (SNP) at the genetic locus encoding β-Microseminoprotein (β-MSP), is associated with both prostate cancer risk and levels of blood prostate-specific antigen (PSA), a biomarker used in prostate cancer screening. Therefore, we wished to determine the association between SNPs at MSMB , the gene encoding β-MSP, and the levels of prostate-produced biomarkers β-MSP, PSA, and human kallikrein 2 (hK2) in blood and semen. Methods: Blood and semen from 304 healthy young Swedish men (ages 18-21) were assayed for β-MSP, PSA, and hK2. SNPs around MSMB were genotyped from matched DNA and analyzed for quantitative association with biomarker levels. Empirical P values were multiple test–corrected and the independence of each SNP's effect was determined. Results: rs10993994 was significantly associated with the blood and semen levels of β-MSP (both P < 1.0 × 10−7) and PSA ( P = 0.00014 and P = 0.0019), and semen levels of hK2 ( P = 0.00027). Additional copies of the prostate cancer risk allele resulted in lower β-MSP but higher PSA levels, and singly explained 23% and 5% of the variation seen in semen β-MSP and PSA, respectively. Additional SNPs at MSMB are associated with β-MSP and PSA independently of rs10993994. Conclusions: SNPs at MSMB correlate with physiologic variation in β-MSP and PSA levels in the blood and semen of healthy young Swedish men. In particular, rs10993994 has a strong effect on β-MSP levels. Impact: Our results suggest a mechanism by which rs10993994 might predispose to prostate cancer and raise the possibility that genetic variation might need to be considered in interpreting the levels of these biomarkers. Cancer Epidemiol Biomarkers Prev; 19(8); 2035–42. ©2010 AACR. This article is featured in Highlights of This Issue, [p. 1887][1] [1]: /lookup/volpage/19/1887
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Blood biomarker levels to aid discovery of cancer-related single-nucleotide polymorphisms: Kallikreins and prostate cancer
Cancer Prevention Research, 2010Co-Authors: Robert J. Klein, Anders S. Bjartell, Angel M Cronin, Alexander Ploner, Peter T Scardino, Fredrik Wiklund, Pär Stattin, Jianfeng Xu, Christer Hallden, Kenneth OffitAbstract:Polymorphisms associated with prostate cancer include those in three genes encoding major secretory products of the prostate: KLK2 (encoding kallikrein-related peptidase 2; hK2), KLK3 (encoding prostate-specific antigen; PSA), and MSMB (encoding Beta-Microseminoprotein). PSA and hK2, members of the kallikrein family, are elevated in sera of men with prostate cancer. In a comprehensive analysis that included sequencing of all coding, flanking, and 2 kb of putative promoter regions of all 15 kallikrein (KLK) genes spanning approximately 280 kb on chromosome 19q, we identified novel single-nucleotide polymorphisms (SNP) and genotyped 104 SNPs in 1,419 cancer cases and 736 controls in Cancer Prostate in Sweden 1, with independent replication in 1,267 cases and 901 controls in Cancer Prostate in Sweden 2. This verified prior associations of SNPs in KLK2 and in MSMB (but not in KLK3) with prostate cancer. Twelve SNPs in KLK2 and KLK3 were associated with levels of PSA forms or hK2 in plasma of control subjects. Based on our comprehensive approach, this is likely to represent all common KLK variants associated with these phenotypes. A T allele at rs198977 in KLK2 was associated with increased cancer risk and a striking decrease of hK2 levels in blood. We also found a strong interaction between rs198977 genotype and hK2 levels in blood in predicting cancer risk. Based on this strong association, we developed a model for predicting prostate cancer risk from standard biomarkers, rs198977 genotype, and rs198977 x hK2 interaction; this model had greater accuracy than did biomarkers alone (area under the receiver operating characteristic curve, 0.874 versus 0.866), providing proof in principle to clinical application for our findings.
