Candidate regions for a testicular cancer susceptibility gene

Leahy, Michael; Tonks, Susan; Moses, J. H.; Brett, Adina; Huddart, Robert; Forman, David; Oliver, R. T. D.; Bishop, D. Timothy; Bodmer, Julia G.

doi:10.1093/hmg/4.9.1551

Cited by 42 publications

(21 citation statements)

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“…However, if a single gene were involved then the magnitude of the increased risk to first-degree relatives indicates that such a gene should be readily mapped (Risch, 1990). In the first major effort to map such a gene, brothers with testicular cancer have been identified and sampled and then a genomic search was performed (Leahy et al, 1995). Evidence for a number of genetic regions has been shown but no one region is unequivocally the site of a testis cancer gene.…”

Section: Discussionmentioning

confidence: 99%

A segregation analysis of testicular cancer based on Norwegian and Swedish families

Heimdal

Olsson²,

Tretli³

et al. 1997

Br J Cancer

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Summary Clustering of testicular cancer cases in families is well known, although the aetiology is not. We present the results of a segregation analysis performed with the algorithm Pointer on familial data on 978 Scandinavian patients with testicular cancer. The segregation analysis favoured the involvement of major gene effects over models incorporating solely polygenic effects in testicular cancer aetiology. Overall, a recessive model best fits the family observations with an estimated gene frequency of 3.8% and a lifetime risk for homozygous men of developing the disease of 43%. This implies that 7.6% of men in the general population will be carriers of the mutant allele and that 0.1% would be homozygote and are, therefore, at high risk of developing the cancer. The testicular cancer incidence has changed greatly during the last generation. Also, the lethality of the disease has changed because of the introduction of new therapy. As failure to take account of such time trends might lead to inappropriate evidence for a recessive model, the analyses were repeated under different assumptions. The analyses favoured a recessive model of inheritance under all assumptions tested. However, the assumptions underlying the analyses are complex and, as this is the first segregation analysis of testicular cancer, the results must be interpreted cautiously.

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Section: Discussionmentioning

confidence: 99%

A segregation analysis of testicular cancer based on Norwegian and Swedish families

Heimdal

Olsson²,

Tretli³

et al. 1997

Br J Cancer

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“…A preliminary linkage study of testicular cancer kindreds identi®ed a number of candidate sites in the human genome, albeit at low LOD scores, including loci at D5S428 and D5S409 (International Testicular Cancer Linkage Consortium, 1998;Leahy et al, 1995). Interestingly, these are precisely the same markers that identify two of the three deleted regions in this study.…”

Section: Discussionmentioning

confidence: 53%

Chromosomal deletions occur in restricted regions of 5q in testicular germ cell cancer

et al. 1999

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Since the biologic behavior and molecular genetic changes observed in testicular germ cell cancer di er from those seen in more common epithelial tumors, it is likely that hitherto uncharacterized genes play a role in the development of germ cell tumors. Our previous work on testicular germ cell cancer suggested that chromosome 5q might contain one or more novel tumor suppressor genes that play a role in this malignancy. In this study, we performed a high resolution loss of heterozygosity (LOH) study of testicular cancer using 37 informative markers on chromosome 5. We detected allelic losses in 20/48 (42%) specimens and identi®ed three common sites of loss on chromosome 5q14, 5q21 and 5q34-qter, de®ned respectively by minimal regions of deletion of 41 cM, 10 cM and *20 (cM). Using an overlapping series of YACs and radiation hybrid mapping, we have constructed a physical map of the 5q14 deletion that should aid in the isolation and characterization of the putative tumor suppressor gene located therein.

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“…Although several candidate genes have been proposed, further research is indicated to clarify the molecular genetic basis and to identify the testicular cancer susceptibility gene(s) (Leahy et al, 1995;International Testicular Cancer Linkage Consortium, 1998;Murty and Chaganti, 1998). Individuals in stable founder populations share a relatively high frequency of genes from common ancestors, i.e.…”

Section: Discussionmentioning

confidence: 99%

Geographic clustering of testicular cancer incidence in the northern part of The Netherlands

et al. 1999

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Geographic variations in testicular cancer incidence may be caused by differences in environmental factors, genetic factors, or both. In the present study, geographic patterns of age-adjusted testicular cancer incidence rates (IRs) in 12 provinces in The Netherlands in the period 1989–1995 were analysed. In addition, the age-adjusted IR of testicular cancer by degree of urbanization was evaluated. Cancer incidence data were obtained from the Netherlands Cancer Registry. The overall annual age-adjusted IR of testicular cancer in The Netherlands in the period 1989–1995 was 4.4 per 100 000 men. The province Groningen in the north of the country showed the highest annual IR with 5.8 per 100 000 men, which was higher ( P < 0.05) than the overall IR in The Netherlands (incidence rate ratio (IRR) 1.3, 95% confidence interval (CI) 1.1–1.6). The highest IR in Groningen was seen for both seminomas and non-seminomas. In addition, Groningen showed the highest age-specific IRs in all relevant younger age groups (15–29, 30–44 and 45–59 years), illustrating the consistency of data. The province Friesland, also situated in the northern part of the country, showed the second highest IR of testicular cancer with 5.3 cases per 100 000 men per year (IRR 1.2, 95% Cl 1.0–1.5, not significant). This mainly resulted from the high IR of seminoma in Friesland. Analysis of age-adjusted IRs of testicular cancer by degree of urbanization in The Netherlands showed no urban–rural differences at analysis of all histological types combined, or at separate analyses of seminomas and non-seminomas. Geographic clustering of testicular cancer seems to be present in the rural north of The Netherlands with some stable founder populations, which are likely to share a relatively high frequency of genes from common ancestors including genes possibly related to testicular cancer. Although this finding does not exclude the involvement of shared environmental factors in the aetiology of testicular cancer, it may also lend support to a genetic susceptibility to testicular cancer development. Testicular cancer cases in stable founder populations seem particularly suitable for searching for testicular cancer susceptibility genes because such genes are likely to be more frequent among affected men in such populations. © 1999 Cancer Research Campaign

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Candidate regions for a testicular cancer susceptibility gene

Cited by 42 publications

References 0 publications

A segregation analysis of testicular cancer based on Norwegian and Swedish families

A segregation analysis of testicular cancer based on Norwegian and Swedish families

Chromosomal deletions occur in restricted regions of 5q in testicular germ cell cancer

Geographic clustering of testicular cancer incidence in the northern part of The Netherlands

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