Unravelling the genetics of prostate cancer

Edwards, Stephen M.; Eeles, Rosalind

doi:10.1002/ajmg.c.30027

Cited by 57 publications

(44 citation statements)

References 94 publications

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“…Although empirical data are available to counsel men about their risk based on family history, 24 providing information about the genetics of prostate cancer is less straightforward because the molecular basis of hereditary prostate cancer predisposition is poorly understood. 13 Still, there may be benefit in responding to misconceptions held by these men about the effect of (hypothetical) genetic testing on health outcomes (Ruth Cowan, BSc, unpublished data) and to lay beliefs about inheritance that are commonly held by families with inherited conditions. 39,40 Although items relating to counseling and peer support were the least endorsed by respondents, approximately half of the respondents did indicate some level of interest in each of these services, and the majority indicated they had not had any or enough support in relation to their family history.…”

Section: Sample Considerationsmentioning

confidence: 99%

“…12 Nonetheless, the molecular basis of susceptibility remains unclear. 13 Currently, it is uncommon for men with a family history suggestive of hereditary prostate cancer to be seen in cancer genetics clinics. In Australia and possibly other countries, this may be due in part to the minimal guidelines for screening or referral of men with a family history of prostate cancer to cancer genetic services.…”

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confidence: 99%

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Genetic services for men: The preferences of men with a family history of prostate cancer

Gaff

Cowan

Meiser

et al. 2006

Genetics in Medicine

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Purpose: Men have a lower uptake of genetic services than women; however, the specific needs and preferences of men at risk of genetic conditions other than hereditary breast ovarian cancer are not known. We ascertain the information preferences of men with a family history of prostate cancer. Methods: Unaffected men and their partners were administered a written questionnaire. Results: Responses were received from 280 men (response rate: 59.2%) and 174 partners (response rate: 74%). Most men (59.6%) reported having insufficient information about their risk and wanted further information about personal risk (93.2%) and risk management (93.6%). Strikingly, 56.3% preferred to receive information related only to positive outcomes. Urologists were the preferred source of information, but there was considerable interest in a multidisciplinary service approach significantly associated with the number of affected relatives (odds ratio ϭ 1.94, P Ͻ .002). Partners' level of concern was not associated with interest in multidisciplinary services, satisfaction with information, or support received. Conclusions: Delivering services to men at risk will require a multifaceted approach by primary care providers and specialists. Challenges include meeting men's expectations in the face of uncertain medical knowledge, engaging those at high risk in multidisciplinary services, and delivering tailored information to those at lower risk. Men have a lower uptake of genetic services 1,2 and genetic testing 3 than women and may have different responses to coping with and disclosing genetic information. 3,4 Despite these differences, men's preferences for genetic service delivery have not been sought or identified. In cancer genetics particularly, the delivery of genetic services has been largely influenced by the experiences of women with, or at risk of developing, hereditary breast-ovarian cancer. 5-7 One retrospective study examined the needs of men with BRCA1 and BRCA2 mutations and found them generally satisfied with genetic counseling, but this did not ascertain preferences. It cannot be assumed that men at risk of other hereditary cancer predispositions have the same needs as men with mutations predisposing predominantly to breast cancer. Understanding men's preferences for the delivery of cancer genetic information becomes important when considering services for men with a family history of prostate cancer. These men have a risk of developing prostate cancer that increases with the number of affected relatives and a decreasing age of diagnosis. 8 -11 An autosomal dominant form (hereditary prostate cancer) has been defined, 8 and 2% to 3% of all prostate cancer cases meet these criteria, with up to one third of cases diagnosed before 60 years possibly caused by dominantly inherited mutations in susceptibility genes. 12 Nonetheless, the molecular basis of susceptibility remains unclear. 13 Currently, it is uncommon for men with a family history suggestive of hereditary prostate cancer to be seen in cancer genetics clinics. In Aus...

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Section: Sample Considerationsmentioning

confidence: 99%

mentioning

confidence: 99%

Genetic services for men: The preferences of men with a family history of prostate cancer

Gaff

Cowan

Meiser

et al. 2006

Genetics in Medicine

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“…Excluding advanced age and African-American ancestries, the strongest risk factor for the disease is a family history of PCa. [4][5][6] PCa is one of the common cancers with a large genetic component, as up to 42% of the risk could be explained by inheritance from studies about twins. 7 Genome-wide association studies (GWAs) have identified 46 susceptibility loci associated with PCa [8][9][10][11][12][13][14][15][16][17][18][19][20] that individually contribute to a small increase in PCa risk, but which taken together, could explain more than 25% of the excess of PCa familial risk.…”

Section: Introductionmentioning

confidence: 99%

“…Higher risks have been shown for men with two or more affected relatives. [4][5][6][7][37][38][39][40] This increase is too great to be explained by non-genetic factors alone. Analyses based on the Nordic twin registries have found higher risks in monozygotic than dizygotic twins, supporting the hypothesis that much of this familial aggregation is due to genetic factors (42%), rather than shared lifestyle factors.…”

Section: Introductionmentioning

confidence: 99%

The role of BRCA1 and BRCA2 in prostate cancer

Castro¹,

Eeles²

2012

Asian J Androl

135

105

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One of the strongest risk factors for prostate cancer is a family history of the disease. Germline mutations in the breast cancer predisposition gene 2 (BRCA2) are the genetic events known to date that confer the highest risk of prostate cancer (8.6-fold in men f65 years). Although the role of BRCA2 and BRCA1 in prostate tumorigenesis remains unrevealed, deleterious mutations in both genes have been associated with more aggressive disease and poor clinical outcomes. The increasing incidence of prostate cancer worldwide supports the need for new methods to predict outcome and identify patients with potentially lethal forms of the disease. As we present here, BRCA germline mutations, mainly in the BRCA2 gene, are one of those predictive factors. We will also discuss the implications of these mutations in the management of prostate cancer and hypothesize on the potential for the development of strategies for sporadic cases with similar characteristics.

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“…Younger ages at diagnosis and multiple affected relatives with the disease tend to be associated with even higher relative risk (2). The disease has a complex etiology, with genetic studies suggesting that multiple genes are important in the onset, progression, and treatment response (9)(10)(11)(12)(13)(14).…”

Section: Introductionmentioning

confidence: 99%

Evaluation of a variant in the transcription factor 7‐like 2 (TCF7L2) gene and prostate cancer risk in a population‐based study

et al. 2008

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Transcription factor 7-like 2 (TCF7L2) is a high mobility group -box containing protein that is a critical member of the Wnt/β-catenin signaling pathway. In addition to its recently recognized role in diabetes, aberrant TCF7L2 expression has been implicated in cancer through regulation of cell proliferation and apoptosis by c-MYC and cyclin D. It has been hypothesized that germline variants within the TCF7L2 gene previously associated with diabetes may affect cancer risk through the Wnt/ β-catenin signaling pathway. Specifically, the same risk allele of single nucleotide polymorphism (SNP) rs12255372 that is associated with diabetes (T allele) has recently been associated with an increased risk of breast cancer.Here, we investigated associations between rs12255372 and prostate cancer risk among 597 cases and 548 controls from a population-based study. We also evaluated prostate cancer progression/ recurrence and prostate-specific mortality among these cases under long-term surveillance. The risk allele was associated with cancer progression/recurrence after primary treatment [hazard ratio (HR) =1.48, 95% confidence interval (CI) =1.01-2.19), but this association was attenuated when the model was further adjusted for Gleason score and tumor stage. There were no associations between this SNP and the risk of developing disease or prostate cancer-specific mortality. Our findings suggest that this variant in the TCF7L2 gene may enhance tumor progression or metastasis, but it does not contribute significantly to tumor initiation. These findings are of clinical importance for identification of patients that may develop more aggressive/recurrent disease after primary treatment.

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Unravelling the genetics of prostate cancer

Cited by 57 publications

References 94 publications

Genetic services for men: The preferences of men with a family history of prostate cancer

Genetic services for men: The preferences of men with a family history of prostate cancer

The role of BRCA1 and BRCA2 in prostate cancer

Evaluation of a variant in the transcription factor 7‐like 2 (TCF7L2) gene and prostate cancer risk in a population‐based study

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