Genome‐wide scan of Swedish families with hereditary prostate cancer: Suggestive evidence of linkage at 5q11.2 and 19p13.3

Wiklund, Fredrik; Gillanders, Elizabeth M.; Albertus, Julie; Bergh, Anders; Damber, Jan Erik; Emanuelsson, Monica; Freas-Lutz, Diana; Gildea, Derek; Göransson, Ingela; Jones, Mary Pat; Jonsson, Björn; Lindmark, Fredrik; Markey, Carol; Riedesel, Erica L.; Stenman, Elisabeth; Trent, J.; Grönberg, Henrik

doi:10.1002/pros.10303

Cited by 61 publications

(35 citation statements)

References 38 publications

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“…Remarkable, however, is a pattern of three of our loci on 19p, 15q and 1p, which were recently reported from a genomewide scan on Swedish HPC families. 30 This similarity may possibly support the hypothesis of a population based genetic heterogeneity.…”

Section: Discussionsupporting

confidence: 55%

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A genomewide linkage analysis for prostate cancer susceptibility genes in families from Germany

et al. 2004

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Prostate cancer is a complex disease with a substantial genetic contribution involved in the disease risk. Several genomewide linkage studies conducted so far have demonstrated a strong heterogeneity of susceptibility. In order to assess candidate regions that are particularly relevant for the German population, we performed a genomewide linkage search on 139 prostate cancer families. A nonparametric method (Z lr scores), using GENEHUNTERPLUS, was applied at 500 markers (panel P1400, deCODE), with an average spacing of 7.25 cM. In the entire family collection, linkage was most evident at 8p22 (Z lr ¼ 2.47, P ¼ 0.0068), close to the previously identified susceptibility gene MSR1. Further local maxima with Z lr 42 (Po0.025) were observed at 1q, 5q and 15q. In a subgroup of 47 families, which matched the Johns Hopkins criteria of hereditary prostate cancer, suggestive linkage was found on 1p31 (Z lr ¼ 3.37, P ¼ 0.00038), a previously not described candidate region. The remaining 92 pedigrees, with no strong disease history, revealed a maximum Z lr ¼ 3.15 (P ¼ 0.00082) at 8q13, possibly indicating a gene with reduced penetrance or recessive inheritance. Our results suggest pronounced locus heterogeneity of prostate cancer susceptibility in Germany. In the present study population, the MSR1 gene could play a significant role. Other conspicuous loci, like 1p31 and 8q13, need further investigation in order to verify their relevance and to identify candidate genes.

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Section: Discussionsupporting

confidence: 55%

“…30 In the late-onset group of their sample, Wiklund et al observed a maximum hLOD score of 1.35 on 1p, 15 cM telomeric from the critical region in our scan. The coincidence of the two independent findings at 1p31 may indicate a new candidate region for hereditary prostate cancer.…”

Section: Discussionmentioning

confidence: 43%

A genomewide linkage analysis for prostate cancer susceptibility genes in families from Germany

et al. 2004

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“…The genomic location of human miR-449a is chromosome 5q11.2, a region identified as a susceptibility locus in a variety of malignancies, including prostate cancer (Pan et al, 2001;Wiklund et al, 2003). We found that miR-449a is frequently downregulated in prostate cancer tissues, relative to patientmatched control tissue.…”

Section: Introductionmentioning

confidence: 74%

“…miR-449a expression was lower in tumor tissue compared to normal patientmatched control tissue. The genomic location of human miR-449a is chromosome 5q11.2, a region identified as a susceptibility locus in prostate cancer (Pan et al, 2001;Wiklund et al, 2003). Loss of miR-449a, an endogenous HDAC-1 inhibitor, may promote aberrant expression of HDAC-1 in prostate cancer contributing to the etiology of the disease.…”

Section: Discussionmentioning

confidence: 99%

miR-449a targets HDAC-1 and induces growth arrest in prostate cancer

et al. 2009

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“…The present author and colleagues are investigating the effect of functional selenoprotein SNPs on prostate cancer risk using DNA samples from 1400 prostate cancer cases and 800 age-and location-matched controls from the Swedish prostate cancer study (Wiklund et al 2003). Careful speciation work (Goenaga-Infante et al 2004, 2005 is also being extended to identify low-molecularweight Se species in body tissues and fluids and in Se-enriched yeast and plants.…”

Section: Current and Future Selenium-cancer Projectsmentioning

confidence: 99%

Selenium in cancer prevention: a review of the evidence and mechanism of action

2005

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Se is an unusual trace element in having its own codon in mRNA that specifies its insertion into selenoproteins as selenocysteine (SeCys), by means of a mechanism requiring a large SeCysinsertion complex. This exacting insertion machinery for selenoprotein production has implications for the Se requirements for cancer prevention. If Se may protect against cancer, an adequate intake of Se is desirable. However, the level of intake in Europe and some parts of the world is not adequate for full expression of protective selenoproteins. The evidence for Se as a cancer preventive agent includes that from geographic, animal, prospective and intervention studies. Newly-published prospective studies on oesophageal, gastric-cardia and lung cancer have reinforced previous evidence, which is particularly strong for prostate cancer. Interventions with Se have shown benefit in reducing the risk of cancer incidence and mortality in all cancers combined, and specifically in liver, prostate, colo-rectal and lung cancers. The effect seems to be strongest in those individuals with the lowest Se status. As the level of Se that appears to be required for optimal effect is higher than that previously understood to be required to maximise the activity of selenoenzymes, the question has been raised as to whether selenoproteins are involved in the anti-cancer process. However, recent evidence showing an association between Se, reduction of DNA damage and oxidative stress together with data showing an effect of selenoprotein genotype on cancer risk implies that selenoproteins are indeed implicated. The likelihood of simultaneous and consecutive effects at different cancer stages still allows an important role for anti-cancer Se metabolites such as methyl selenol formed from g-glutamyl-selenomethyl-SeCys and selenomethyl-SeCys, components identified in certain plants and Se-enriched yeast that have anti-cancer effects. There is some evidence that Se may affect not only cancer risk but also progression and metastasis. Current primary and secondary prevention trials of Se are underway in the USA, including the Selenium and Vitamin E Cancer Prevention Trial (SELECT) relating to prostate cancer, although a large European trial is still desirable given the likelihood of a stronger effect in populations of lower Se status.

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Genome‐wide scan of Swedish families with hereditary prostate cancer: Suggestive evidence of linkage at 5q11.2 and 19p13.3

Abstract: Our results provide strong confirmatory evidence of linkage at 19q13.3 and 5q11.2. The lack of confirmation of linkage at several loci identified in other genome-wide scans emphasizes the need to combine linkage data between research groups.

Cited by 61 publications

References 38 publications

A genomewide linkage analysis for prostate cancer susceptibility genes in families from Germany

A genomewide linkage analysis for prostate cancer susceptibility genes in families from Germany

miR-449a targets HDAC-1 and induces growth arrest in prostate cancer

Selenium in cancer prevention: a review of the evidence and mechanism of action

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