Familial Factors in Bladder Carcinoma

Lynch, Henry T.; Walzak, Myron P.; Fried, Rainer; Domina, Alan H.; Lynch, Jane F.

doi:10.1016/s0022-5347(17)56461-7

Cited by 38 publications

(12 citation statements)

References 13 publications

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“…Previously published clinical reports have indicated a possible familial component to bladder cancer. [2][3][4][5] Early age at onset in probands and aggregation of cases within families are consistent with a hereditary etiology. There have been a limited number of epidemiologic studies investigating the familial risk of bladder cancer, and the results have been inconsistent.…”

mentioning

confidence: 79%

“…Familial aggregation of bladder cancer has been described in several clinical case reports. [2][3][4][5] It has been proposed that the aggregation pattern represents an example of Lynch syndrome II, a form of hereditary nonpolyposis colorectal cancer with extracolonic cancer sites, including transitional cell carcinoma of the bladder and urinary tract. [18][19][20] Among epidemiologic studies that support familial aggregation of bladder cancer, Kramer et al 6 compared bladder cancer incidence between first-degree relatives of 319 case probands and 319 control probands.…”

Section: Discussionmentioning

confidence: 99%

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Bladder cancer risk as modified by family history and smoking

Lin

Spitz

Dinney

et al. 2006

Cancer

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This study investigated the ability of MnCl2 as a cellular MRI contrast agent to determine the in vitro viability of human embryonic stem cells (hESC) and human bone marrow stromal cells (hBMSC). Basic MRI parameters including T1 and T2 values of MnCl2‐labeled hESC and hBMSC were measured and viability signal of manganese (Mn2+)‐labeled cells was validated. Furthermore, the biological activity of Ca2+‐channels was modulated utilizing both Ca2+‐channel agonist and antagonist to evaluate concomitant signal changes. Metabolic effects of MnCl2‐labeling were also assessed using assays for cell viability, proliferation, and apoptosis. Finally, in vivo Mn2+‐guided MRI of the transplanted hESC was successfully achieved and validated by bioluminescence imaging. Magn Reson Med, 2009. © 2009 Wiley‐Liss, Inc.

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mentioning

confidence: 79%

Section: Discussionmentioning

confidence: 99%

Bladder cancer risk as modified by family history and smoking

Lin

Spitz

Dinney

et al. 2006

Cancer

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“…17 Previously published clinical reports have indicated a possible familial component to bladder cancer. [31][32][33][34] There is a significantly increased risk of bladder cancer among firstdegree relatives of individuals who have bladder cancer, with an earlier age of disease onset. [35][36][37] In a large twin study, environmental factors were estimated to contribute a significant 69% to bladder cancer risk, whereas inherited genetic factors contributed a nonsignificant 31% of risk.…”

Section: Bladder Cancer Carcinogenesismentioning

confidence: 99%

The origins of bladder cancer

Crawford

2008

Laboratory Investigation

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Bladder cancer, arising from the transitional cells of the mucosal urothelium, may present as a noninvasive, papillary tumor protruding from the mucosal surface, or as a solid, nonpapillary tumor that invades the bladder wall and has a high propensity for metastasis. The nonpapillary tumors originate from in situ dysplasia. The most common environmental risk for bladder cancer is active smoking; occupational exposure to arsenic or other carcinogens is also a risk factor. A possible familial component to bladder cancer has been described. Conventional models of carcinogenesis suppose the existence of successive mutation events within a specific cell clone, enabling its eventual escape from regulation of cell division and maintenance of genomic integrity. Important new information has emerged from whole-organ mapping of the mucosal genome in bladders resected for invasive cancer (Majewski et al, Lab Invest; published online 5 May 2008). Mapping of genetic hits across the entire mucosa demonstrates genetic alterations in six chromosomal regions, not only in mucosal regions of evident dysplasia, but also in morphologically normal mucosa. These clonally expanded regions cover vast expanses of the bladder surface, as a 'first wave' of pre-neoplasia. Target genes in these regions are termed 'forerunner genes' (FR genes), based on the concept that these genes enable the initial clonal expansion of in situ urothelial neoplasia. Extensive further analysis of human populations with urothelial cancer implicates genetic polymorphisms in one of these genes, P2RY5, as being present in a familial cluster of cancers of multiple organs, and as imparting risk for development of bladder cancer in active smokers. P2RY5 is a gene encoded within intron 17 of RB1, a prototypic tumor suppressor gene whose expression is lost at a later stage of bladder carcinogenesis. Alterations of the FR gene status provide a novel opportunity to screen individuals at risk for the earliest stage of bladder pre-neoplasia and represent attractive targets for therapeutic and chemopreventive interventions. These findings support the hypothesis that bladder carcinogenesis is initiated by clonal expansion of genetically altered but histologically normal cells that cover broad expanses of the mucosa. Effort must now be given to identifying the biological function of these novel FR genes. KEYWORDS: bladder cancer; forerunner genes; P2RY5; RB1; whole-organ mapping; genomic mapping EPIDEMIOLOGY OF BLADDER CANCER Bladder cancer is the fourth most incident cancer in males and ninth most incident in females. In the United States, over 67 000 new cases are diagnosed per year, 1 and over 350 000 cases diagnosed worldwide. 2 In the United States, the annual age-adjusted incidence rate for men is approximately 32 per 100 000. 3 Men have a higher risk of bladder cancer than women, by a rate ratio of at least 3:1. Approximately 66% of bladder cancers are diagnosed among individuals age 65 years or older.Bladder cancer arises primarily from the transitional cells of the b...

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“…[25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41] The number of cases per family was two (n=15), three (n=15), six (n=1), and one family with 5 TCCUT and one squamous cell bladder cancer. When tumor site was specified, eleven families had bladder TCC only, nine included TCC of the bladder and renal pelvis/ureter, and one presented only ureteral cancer.…”

Section: Case Reports Of Familial Tccutmentioning

confidence: 99%

“…[2] Furthermore, a genetic predisposition to bladder cancer is suggested by the occurrence of TCCUT in several Mendelian disorders [8][9][10][11], epidemiologic studies showing that a positive TCCUT family history increases bladder cancer risk [12][13][14][15][16][17][18][19][20][21][22][23][24], and a limited number of case reports describing multiple-case TCCUT families. [25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41] Therefore, both genetic and environmental factors play a role in the development of bladder and related urinary tract cancers. Here we update a previously-reported family, report a new multiple-case kindred, critically review the familial TCCUT literature, and provide a brief summary of genetic factors that have been implicated in TCCUT risk.…”

Section: Introductionmentioning

confidence: 99%

Familial and genetic risk of transitional cell carcinoma of the urinary tract

Mueller¹,

Caporaso²,

Greene³

2008

Urologic Oncology: Seminars and Original Investigations

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Environmental exposures, including tobacco smoke and occupational exposure to aromatic amines, have been implicated in bladder cancer etiology. However, the pathogenesis of urinary bladder transitional cell carcinoma remains incompletely defined. In epidemiologic studies, family history confers a two-fold increase in bladder cancer risk, but it is uncertain whether this represents evidence of a genetic and/or a shared environmental basis for familial aggregation. Polymorphisms in genes involved in the metabolism of environmental toxins (e.g., NAT2) clearly modify individual susceptibility to bladder cancer. A genetic predisposition has also been suggested by case reports describing multiple-case families, and the development of bladder cancer in association with several well-described Mendelian disorders (e.g., HNPCC, retinoblastoma). Here we update a previouslyreported family, report a new multiple-case kindred, critically review previously-reported bladder cancer families and the epidemiologic literature related to family history of transitional cell carcinoma of the urinary tract (TCCUT) as a risk factor, as well as provide a brief summary of genetic factors that have been implicated in TCCUT risk. We conclude that familial TCCUT is either very uncommon or significantly under-reported, perhaps on the assumption that this is an environmental rather than a genetic disorder. The interaction between multiple genetic and environmental factors has made it challenging to identify genetic components responsible for many common diseases; therefore, a proposed genome-wide association study (GWAS) for urinary bladder cancer may help to clarify the etiologic role of the candidate genetic pathways reviewed here, as well as characterize gene/environment interactions that contribute to TCCUT carcinogenesis.

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Familial Factors in Bladder Carcinoma

Cited by 38 publications

References 13 publications

Bladder cancer risk as modified by family history and smoking

Bladder cancer risk as modified by family history and smoking

The origins of bladder cancer

Familial and genetic risk of transitional cell carcinoma of the urinary tract

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