Literature DB >> 28626070

Potential Susceptibility Loci Identified for Renal Cell Carcinoma by Targeting Obesity-Related Genes.

Xiang Shu1, Mark P Purdue2, Yuanqing Ye1, Huakang Tu1, Christopher G Wood3, Nizar M Tannir4, Zhaoming Wang2, Demetrius Albanes2, Susan M Gapstur5, Victoria L Stevens5, Nathaniel Rothman2, Stephen J Chanock2, Xifeng Wu6.   

Abstract

Background: Obesity is an established risk factor for renal cell carcinoma (RCC). Although genome-wide association studies (GWAS) of RCC have identified several susceptibility loci, additional variants might be missed due to the highly conservative selection.
Methods: We conducted a multiphase study utilizing three independent genome-wide scans at MD Anderson Cancer Center (MDA RCC GWAS and MDA RCC OncoArray) and National Cancer Institute (NCI RCC GWAS), which consisted of a total of 3,530 cases and 5,714 controls, to investigate genetic variations in obesity-related genes and RCC risk.
Results: In the discovery phase, 32,946 SNPs located at ±10 kb of 2,001 obesity-related genes were extracted from MDA RCC GWAS and analyzed using multivariable logistic regression. Proxies (R2 > 0.8) were searched or imputation was performed if SNPs were not directly genotyped in the validation sets. Twenty-one SNPs with P < 0.05 in both MDA RCC GWAS and NCI RCC GWAS were subsequently evaluated in MDA RCC OncoArray. In the overall meta-analysis, significant (P < 0.05) associations with RCC risk were observed for SNP mapping to IL1RAPL2 [rs10521506-G: ORmeta = 0.87 (0.81-0.93), Pmeta = 2.33 × 10-5], PLIN2 [rs2229536-A: ORmeta = 0.87 (0.81-0.93), Pmeta = 2.33 × 10-5], SMAD3 [rs4601989-A: ORmeta = 0.86 (0.80-0.93), Pmeta = 2.71 × 10-4], MED13L [rs10850596-A: ORmeta = 1.14 (1.07-1.23), Pmeta = 1.50 × 10-4], and TSC1 [rs3761840-G: ORmeta = 0.90 (0.85-0.97), Pmeta = 2.47 × 10-3]. We did not observe any significant cis-expression quantitative trait loci effect for these SNPs in the TCGA KIRC data.Conclusions: Taken together, we found that genetic variation of obesity-related genes could influence RCC susceptibility.Impact: The five identified loci may provide new insights into disease etiology that reveal importance of obesity-related genes in RCC development. Cancer Epidemiol Biomarkers Prev; 26(9); 1436-42. ©2017 AACR. ©2017 American Association for Cancer Research.

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Year:  2017        PMID： 28626070      PMCID： PMC5581698          DOI： 10.1158/1055-9965.EPI-17-0141

Source DB:  PubMed          Journal:  Cancer Epidemiol Biomarkers Prev        ISSN： 1055-9965            Impact factor:   4.254


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Authors:  Cecilia Garlanda; Charles A Dinarello; Alberto Mantovani
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2.  A frameshift mutation in MC4R associated with dominantly inherited human obesity.

Authors:  G S Yeo; I S Farooqi; S Aminian; D J Halsall; R G Stanhope; S O'Rahilly
Journal:  Nat Genet       Date:  1998-10       Impact factor: 38.330

3.  A frameshift mutation in human MC4R is associated with a dominant form of obesity.

Authors:  C Vaisse; K Clement; B Guy-Grand; P Froguel
Journal:  Nat Genet       Date:  1998-10       Impact factor: 38.330

Review 4.  The TSC1-TSC2 complex: a molecular switchboard controlling cell growth.

Authors:  Jingxiang Huang; Brendan D Manning
Journal:  Biochem J       Date:  2008-06-01       Impact factor: 3.857

Review 5.  The interleukin-1 receptor family.

Authors:  Diana Boraschi; Aldo Tagliabue
Journal:  Semin Immunol       Date:  2013-11-15       Impact factor: 11.130

6.  Genome-wide association study of renal cell carcinoma identifies two susceptibility loci on 2p21 and 11q13.3.

Authors:  Mark P Purdue; Mattias Johansson; Diana Zelenika; Jorge R Toro; Ghislaine Scelo; Lee E Moore; Egor Prokhortchouk; Xifeng Wu; Lambertus A Kiemeney; Valerie Gaborieau; Kevin B Jacobs; Wong-Ho Chow; David Zaridze; Vsevolod Matveev; Jan Lubinski; Joanna Trubicka; Neonila Szeszenia-Dabrowska; Jolanta Lissowska; Péter Rudnai; Eleonora Fabianova; Alexandru Bucur; Vladimir Bencko; Lenka Foretova; Vladimir Janout; Paolo Boffetta; Joanne S Colt; Faith G Davis; Kendra L Schwartz; Rosamonde E Banks; Peter J Selby; Patricia Harnden; Christine D Berg; Ann W Hsing; Robert L Grubb; Heiner Boeing; Paolo Vineis; Françoise Clavel-Chapelon; Domenico Palli; Rosario Tumino; Vittorio Krogh; Salvatore Panico; Eric J Duell; José Ramón Quirós; Maria-José Sanchez; Carmen Navarro; Eva Ardanaz; Miren Dorronsoro; Kay-Tee Khaw; Naomi E Allen; H Bas Bueno-de-Mesquita; Petra H M Peeters; Dimitrios Trichopoulos; Jakob Linseisen; Börje Ljungberg; Kim Overvad; Anne Tjønneland; Isabelle Romieu; Elio Riboli; Anush Mukeria; Oxana Shangina; Victoria L Stevens; Michael J Thun; W Ryan Diver; Susan M Gapstur; Paul D Pharoah; Douglas F Easton; Demetrius Albanes; Stephanie J Weinstein; Jarmo Virtamo; Lars Vatten; Kristian Hveem; Inger Njølstad; Grethe S Tell; Camilla Stoltenberg; Rajiv Kumar; Kvetoslava Koppova; Olivier Cussenot; Simone Benhamou; Egbert Oosterwijk; Sita H Vermeulen; Katja K H Aben; Saskia L van der Marel; Yuanqing Ye; Christopher G Wood; Xia Pu; Alexander M Mazur; Eugenia S Boulygina; Nikolai N Chekanov; Mario Foglio; Doris Lechner; Ivo Gut; Simon Heath; Hélène Blanche; Amy Hutchinson; Gilles Thomas; Zhaoming Wang; Meredith Yeager; Joseph F Fraumeni; Konstantin G Skryabin; James D McKay; Nathaniel Rothman; Stephen J Chanock; Mark Lathrop; Paul Brennan
Journal:  Nat Genet       Date:  2010-12-05       Impact factor: 38.330

7.  Smad3 deficiency in mice protects against insulin resistance and obesity induced by a high-fat diet.

Authors:  Chek Kun Tan; Nicolas Leuenberger; Ming Jie Tan; Yew Wai Yan; Yinghui Chen; Ravi Kambadur; Walter Wahli; Nguan Soon Tan
Journal:  Diabetes       Date:  2011-02       Impact factor: 9.461

8.  HaploReg: a resource for exploring chromatin states, conservation, and regulatory motif alterations within sets of genetically linked variants.

Authors:  Lucas D Ward; Manolis Kellis
Journal:  Nucleic Acids Res       Date:  2011-11-07       Impact factor: 16.971

9.  MicroRNA profiling in clear cell renal cell carcinoma tissues potentially links tumorigenesis and recurrence with obesity.

Authors:  X Shu; M A Hildebrandt; J Gu; N M Tannir; S F Matin; J A Karam; C G Wood; X Wu
Journal:  Br J Cancer       Date:  2016-12-01       Impact factor: 7.640

10.  Obesity gene atlas in mammals.

Authors:  Tanja Kunej; Dasa Jevsinek Skok; Minja Zorc; Ana Ogrinc; Jennifer J Michal; Milena Kovac; Zhihua Jiang
Journal:  J Genomics       Date:  2013-12-01
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Review 1.  Renal Cell Cancer and Obesity.

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Journal:  Int J Mol Sci       Date:  2022-03-21       Impact factor: 5.923
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