Common variants at 11q12, 10q26 and 3p11.2 are associated with prostate cancer susceptibility in Japanese

Akamatsu, Shusuke; Takata, Ryo; Haiman, Christopher A.; Takahashi, Atsushi; Inoue, Takahiro; Kubo, Michiaki; Furihata, Mutsuo; Kamatani, Naoyuki; Inazawa, Johji; Chen, Gary K.; Marchand, Loı̈c Le; Kolonel, Laurence N.; Katoh, Takahiko; Yamano, Yuko; Yamakado, Minoru; Takahashi, Hiroyuki; Yamada, Hiroki; Egawa, Shin; Fujioka, Tomoaki; Henderson, Brian E.; Habuchi, Tomonori; Ogawa, Osamu; Nakamura, Yusuke; Nakagawa, Hidewaki

doi:10.1038/ng.1104

Cited by 97 publications

(99 citation statements)

References 25 publications

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“…The remaining 18 of 26 genome-wide significant associations were clear replications of previously-reported findings at 2p11.2, 3p11.2, 4q24, 6q22.1, 7p15.2, 8p21.2, 8q24.21, 10q11.23, 11q13.3, 12q13.12, 12q13.13, 17q12, 17q24.3, 19q13.33, and 22q13.2 (Figure 1) (7–9,9–16,24–28). Our 18 lead risk SNPs did not appear to improve upon or exhibit independence from those previously-reported.…”

Section: Resultssupporting

confidence: 84%

“…Eight years of genome-wide association studies (GWAS) identified at least 105 risk variants for PCa (7–28); most are common with modest effects, and alone explain little heritability. However, an overall genetic risk score combining these variants could be substantially more predictive of disease and explain a reasonable heritability proportion, although there still remain undiscovered loci.…”

Section: Introductionmentioning

confidence: 99%

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A Large Multiethnic Genome-Wide Association Study of Prostate Cancer Identifies Novel Risk Variants and Substantial Ethnic Differences

et al. 2015

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A genome-wide association study of prostate cancer in Kaiser Permanente health plan members (7,783 cases, 38,595 controls; 80.3% non-Hispanic white, 4.9% African-American, 7.0% East Asian, 7.8% Latino) revealed a new independent risk indel rs4646284 at the previously-identified locus 6q25.3 that replicated in PEGASUS (N=7,539) and MEC (N=4,679) (p=1.0×10−19, OR=1.18). Across the 6q25.3 locus, rs4646284 exhibited the strongest association with expression of SLC22A1 (p=1.3×10−23) and SLC22A3 (p=3.2×10−52). At the known 19q13.33 locus rs2659124 (p=1.3×10−13, OR=1.18) nominally replicated in PEGASUS. A risk score of 105 known risk SNPs was strongly associated with prostate cancer (p<1.0×10−8). Comparing the highest to lowest risk score deciles, the OR was 6.22 for non-Hispanic Whites, 5.82 for Latinos, 3.77 for African-Americans, and 3.38 for East Asians. In non-Hispanic whites, the 105 risk SNPs explained ~7.6% of disease heritability. The entire GWAS array explained ~33.4% of heritability, with a 4.3-fold enrichment within DNaseI hypersensitivity sites (p=0.004).

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Section: Resultssupporting

confidence: 84%

Section: Introductionmentioning

confidence: 99%

A Large Multiethnic Genome-Wide Association Study of Prostate Cancer Identifies Novel Risk Variants and Substantial Ethnic Differences

et al. 2015

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“…It is therefore likely that VK2-induced ROS generation occurs upstream of Bak and induces apoptosis in a Bakdependent manner, possibly by controlling its modification by VK2-O. Fourth, a recent study in human prostate cancer LNCaP cells demonstrated that VK2-induced anticancer effects are abrogated by GGCX knockdown (Akamatsu et al, 2012), which probably inhibits the generation of VK2-O and prevents the covalent modification of Bak. Thus we established a strong correlation between the covalent attachment of VK2-O and apoptosis induction.…”

Section: Discussionmentioning

confidence: 99%

Vitamin K2 Covalently Binds to Bak and Induces Bak-Mediated Apoptosis

et al. 2012

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Vitamin K2 (VK2, menaquinone) is known to have anticancer activity in vitro and in vivo. Although its effect is thought to be mediated, at least in part, by the induction of apoptosis, the underlying molecular mechanism remains elusive. Here, we identified Bcl-2 antagonist killer 1 (Bak) as a molecular target of VK2-induced apoptosis. VK2 directly interacts with Bak and induces mitochondrial-mediated apoptosis. Although Bak and Bcl-2-associated X protein (Bax), another member of the Bcl-2 family, are generally thought to be functionally redundant, only Bak is necessary and sufficient for VK2-induced cytochrome c (cyt c) release and cell death. Moreover, VK2-2,3 epoxide, an intracellular metabolite of VK2, was shown to covalently bind to the cysteine-166 residue of Bak. Several lines of evidence suggested that the covalent attachment of VK2 is critical for apoptosis induction. Thus this study reveals a specific role for Bak in mitochondria-mediated apoptosis. This study also provides insight into the anticancer effects of VK2 and suggests that Bak may be a potential target of cancer therapy.

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“…The upregulated genes were also enriched in genes involved in cell cycle, DNA metabolism, biopolymer metabolism, and homeobox genes involved in development. This included well-known pan-cancer genes such as TERT, PRAME, and TOP2A (17, 18) and MYEOV and MNX1, which are implicated in blood malignancies (19,20) and FAM111B in prostate cancer (21).…”

Section: Potential Pan-cancer Biomarkersmentioning

confidence: 99%

Transcriptome Analysis of Recurrently Deregulated Genes across Multiple Cancers Identifies New Pan-Cancer Biomarkers

Kaczkowski¹,

Tanaka

Kawaji

et al. 2016

Cancer Research

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Genes that are commonly deregulated in cancer are clinically attractive as candidate pan-diagnostic markers and therapeutic targets. To globally identify such targets, we compared Cap Analysis of Gene Expression profiles from 225 different cancer cell lines and 339 corresponding primary cell samples to identify transcripts that are deregulated recurrently in a broad range of cancer types. Comparing RNA-seq data from 4,055 tumors and 563 normal tissues profiled in the The Cancer Genome Atlas and FANTOM5 datasets, we identified a core transcript set with theranostic potential. Our analyses also revealed enhancer RNAs, which are upregulated in cancer, defining promoters that overlap with repetitive elements (especially SINE/Alu and LTR/ERV1 elements) that are often upregulated in cancer. Lastly, we documented for the first time upregulation of multiple copies of the REP522 interspersed repeat in cancer. Overall, our genomewide expression profiling approach identified a comprehensive set of candidate biomarkers with pan-cancer potential, and extended the perspective and pathogenic significance of repetitive elements that are frequently activated during cancer progression.Cancer Res; 76(2); 216-26. Ó2015 AACR.

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Common variants at 11q12, 10q26 and 3p11.2 are associated with prostate cancer susceptibility in Japanese

Cited by 97 publications

References 25 publications

A Large Multiethnic Genome-Wide Association Study of Prostate Cancer Identifies Novel Risk Variants and Substantial Ethnic Differences

A Large Multiethnic Genome-Wide Association Study of Prostate Cancer Identifies Novel Risk Variants and Substantial Ethnic Differences

Vitamin K2 Covalently Binds to Bak and Induces Bak-Mediated Apoptosis

Transcriptome Analysis of Recurrently Deregulated Genes across Multiple Cancers Identifies New Pan-Cancer Biomarkers

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