Genome-wide association study identified SNP on 15q24 associated with bladder cancer risk in Japanese population

Matsuda, Koichi; Takahashi, Atsushi; Middlebrooks, Candace D.; Obara, Wataru; Nasu, Yasutomo; Inoue, Keiji; Tamura, Kenji; Yamasaki, Ichiro; Naya, Yoshio; Tanikawa, Chizu; Cui, Ri; Figueroa, Jonine D.; Silverman, Debra T.; Rothman, Nathaniel; Namiki, Mikio; Tomita, Yoshihiko; Nishiyama, Hiroyuki; Kohri, Kenjiro; Deguchi, Takashi; Nakagawa, Masayuki; Yokoyama, Masayoshi; Miki, Tsuneharu; Kumon, Hiromi; Fujioka, Tomoaki; Prokunina‐Olsson, Ludmila; Kubo, Michiaki; Nakamura, Yusuke; Shuin, Taro

doi:10.1093/hmg/ddu512

Cited by 37 publications

(33 citation statements)

References 45 publications

(44 reference statements)

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“…Furthermore, genome-wide association studies (GWAS) have identified a subset of common variants associated with bladder cancer risk (5)(6)(7)(8)(9)(10)(11)(12)(13)(14). However, these studies have primarily been conducted in individuals of European descent, and only one GWAS reported by Matsuda and colleagues had been performed in Japanese (14).…”

Section: Introductionmentioning

confidence: 99%

Genome-Wide Association Study of Bladder Cancer in a Chinese Cohort Reveals a New Susceptibility Locus at 5q12.3

Wang

Chu

et al. 2016

Cancer Research

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Genome-wide association studies (GWAS) of bladder cancer have identified a number of susceptibility loci in European populations but have yet to uncover the genetic determinants underlying bladder cancer incidence among other ethnicities. Therefore, we performed the first GWAS in a Chinese cohort comprising 3,406 cases of bladder cancer and 4,645 controls. We identified a new susceptibility locus for bladder cancer at 5q12.3, located in the intron of CWC27

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Section: Introductionmentioning

confidence: 99%

Genome-Wide Association Study of Bladder Cancer in a Chinese Cohort Reveals a New Susceptibility Locus at 5q12.3

Wang

Chu

et al. 2016

Cancer Research

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“…A small-scale case-control study has revealed the association of CYP2A6*1/*4 or *4/ *4 genotypes with decreased susceptibility to bladder cancer [48]; however, the relationship between CYP2A6 SNPs and bladder cancer risk has not been demonstrated by GWASs [13–17]. Recently, Matsuda et al have reported that CYP1A2, another member of the CYP family of enzymes thought to metabolize tobacco-derived carcinogens, is associated with bladder cancer risk in Japanese population [18]. However, that study did not discriminate between non-invasive and invasive bladder cancers; therefore, CYP2A6 contribution to the risk of developing invasive bladder cancer phenotype could not be clearly determined.…”

Section: Discussionmentioning

confidence: 99%

“…Using candidate-gene approach, a previous study has demonstrated the association between an increased risk of bladder cancer and deletion of the GSTM1 gene on human chromosome 1p13.3, which is involved in the metabolism of carcinogens [12]. Many GWASs revealed a correlation between an increased risk of bladder cancer and single nucleotide polymorphisms (SNPs) [13–18]. …”

Section: Introductionmentioning

confidence: 99%

Genomic Landscape of Experimental Bladder Cancer in Rodents and Its Application to Human Bladder Cancer: Gene Amplification and Potential Overexpression of Cyp2a5/CYP2A6 Are Associated with the Invasive Phenotype

Kanemoto¹,

Fukuta

Kawai

et al. 2016

PLoS ONE

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Non-muscle invasive (superficial) bladder cancer is a low-grade malignancy with good prognosis, while muscle invasive (invasive) bladder cancer is a high-grade malignancy with poor prognosis. N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) induces superficial bladder cancers with papillary morphology in rats and invasive bladder cancers with infiltrating phenotype in mice. In this study, we analyzed genomic landscapes of rodent BBN-induced bladder cancers using array-based comparative genomic hybridization (array CGH). While no significant copy number alterations were detected in superficial bladder tumors in rats, copy number gains in chromosomal regions 2D-E1, 7qA3, 9F2, and 11C-D were detected in invasive bladder tumors in mice. Amplification of representative genes located on 2D-E1 and 7qA3 chromosomal regions was confirmed by quantitative PCR. Cyp2a22 and Cyp2a5 genes but not Cyp2g1, Cyp2a12, and Rab4b genes on mouse chromosome 7qA3 were amplified in invasive bladder cancers. Although the human ortholog gene of Cyp2a22 has not been confirmed, the mouse Cyp2a5 gene is the ortholog of the human CYP2A6 gene located in chromosomal region 19q13.2, and CYP2A6 was identified by database search as one of the closest human homolog to mouse Cyp2a22. Considering a possibility that this region may be related to mouse 7qA3, we analyzed CYP2A6 copy number and expression in human bladder cancer using cell lines and resected tumor specimens. Although only one of eight cell lines showed more than one copy increase of the CYP2A6 gene, CYP2A6 amplification was detected in six out of 18 primary bladder tumors where it was associated with the invasive phenotype. Immunohistochemical analyses of 118 primary bladder tumors revealed that CYP2A6 protein expression was also higher in invasive tumors, especially in those of the scattered type. Together, these findings indicate that the amplification and overexpression of the CYP2A6 gene are characteristic of human bladder cancers with increased malignancy and that CYP2A6 can be a candidate prognostic biomarker in this type of cancer.

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“…We used UCSC Genome Browser to select SNPs within the gene region and SNPs flanking 500 bp of the gene boundary. (41,42). The standard protocol for genome-wide analyses was used for quality control (43).…”

Section: Selection Of Et-1 Pathway Candidate Genesmentioning

confidence: 99%

Endothelin-1 Pathway Polymorphisms and Outcomes in Pulmonary Arterial Hypertension

Benza

Gomberg‐Maitland

DeMarco

et al. 2015

Am J Respir Crit Care Med

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Rationale: Pulmonary arterial hypertension (PAH) is a progressive fatal disease. Variable response and tolerability to PAH therapeutics suggests that genetic differences may influence outcomes. The endothelin pathway is central to pulmonary vascular function, and several polymorphisms and/or mutations in the genes coding for endothelin (ET)-1 and its receptors correlate with the clinical manifestations of other diseases.Objectives: To examine the interaction of ET-1 pathway polymorphisms and treatment responses of patients with PAH treated with ET receptor antagonists (ERAs).Methods: A total of 1,198 patients with PAH were prospectively enrolled from 45 U.S. and Canadian pulmonary hypertension centers or retrospectively from global sites participating in the STRIDE (Sitaxsentan To Relieve Impaired Exercise) trials. Comprehensive objective measures including a 6-minute-walk test, Borg dyspnea score, functional class, and laboratory studies were completed at baseline, before the initiation of ERAs, and repeated serially. Singlenucleotide polymorphisms from ET-1 pathway candidate genes were selected from a completed genome-wide association study performed on the study cohort.Measurements and Main Results: Patient efficacy outcomes were analyzed for a relationship between ET-1 pathway polymorphisms and clinical efficacy using predefined, composite positive and negative outcome measures in 715 European descent samples. A single-nucleotide polymorphism (rs11157866) in the G-protein alpha and gamma subunits gene was significantly associated, accounting for multiple testing, with a combined improvement in functional class and 6-minute-walk distance at 12 and 18 months and marginally significant at 24 months.Conclusions: ET-1 pathway associated polymorphisms may influence the clinical efficacy of ERA therapy for PAH. Further prospective studies are needed.

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Genome-wide association study identified SNP on 15q24 associated with bladder cancer risk in Japanese population

Cited by 37 publications

References 45 publications

Genome-Wide Association Study of Bladder Cancer in a Chinese Cohort Reveals a New Susceptibility Locus at 5q12.3

Genome-Wide Association Study of Bladder Cancer in a Chinese Cohort Reveals a New Susceptibility Locus at 5q12.3

Genomic Landscape of Experimental Bladder Cancer in Rodents and Its Application to Human Bladder Cancer: Gene Amplification and Potential Overexpression of Cyp2a5/CYP2A6 Are Associated with the Invasive Phenotype

Endothelin-1 Pathway Polymorphisms and Outcomes in Pulmonary Arterial Hypertension

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