|Grant Number:||5R01CA100264-05 Interpret this number|
|Primary Investigator:||Wei, Qingyi|
|Organization:||University Of Tx Md Anderson Can Ctr|
|Project Title:||Genetic Predictors for DNA Repair Phenotype in Cmm|
DESCRIPTION (provided by applicant): Cutaneous malignant melanoma (CMM) is the most serious form of skin cancer. Sunlight has for a long time been suspected to cause CMM. It is predicted that the incidence of CMM will continue to increase as a result of the continuous decrease in the concentration of stratospheric ozone and increased leisure time for sunlight-related recreations such as sunbathing, which will increase exposure to solar ultraviolet (UV) B radiation responsible for inducing DNA damage in humans. Our recently completed case-control study provides evidence that low DNA repair for UV-induced DNA damage (as measured by a host-cell reactivation (HCR) assay) may contribute to sporadic CMM in the general population. These seven xeroderma pigmentosum (XP) genes (i.e., XPA, XPB/excision repair cross-complementing group 3 (ERCC3), XPC, XPD/ERCC2, XPE/damaged DNA-binding protein (DDB1), XPF/ERCC4 and XPG/ERCC5)code for core proteins involved in the nucleotide excision repair (NER) pathway that effectively repairs UV-damaged DNA including photoproducts such as cyclobutane pyrimidine dimers (CPDs) and (6-4) photoproducts (6-4PPs). Our preliminary data suggest that a combined genotype of XPC and XPD predicts DNA repair phenotype as measured by the HCR assay. We propose to identify a combination of functional polymorphisms of these seven NER genes that predicts DNA repair phenotype in CMM using a case series analysis. Our specific Aims are: Aim 1. To accrue a case series of 800 incident CMM with blood sample collection and to develop a comprehensive database of complete assessment of epidemiological risk factors, whole body skin examination, and genotypic and phenotypic biomarkers for the NER. Aim 2. To determine phenotypic and genotypic characteristics of NER in these CMM patients; and Aim 3. To determine the correlation between DNA repair genotype and phenotype and identify a combined NER pathway genotype that best predicts the DNA repair phenotype. These aims are achievable, because it is biologically plausible that DRC may be determined by genetic polymorphisms of genes that participate in NER, which is measured by DRC. Our preliminary data have shown that individuals with suboptimal DRC are at risk of developing CMM and that a combined genotype of three polymorphisms of XPC and XPD is a reasonable predictor of the DRC phenotype. Because the phenotypic DNA repair assay requires cell cultures with viable cells and is too labor-intensive for large molecular epidemiological studies, it is important to identify genotypic markers that predict such DNA repair phenotype so that they can be used for future screening for individuals with genetic susceptibility to development of CMM in the general population. When the combined NER genotype representing genetic susceptibility to CMM is identified and is confirmed in the general population, it may have a significant impact on primary prevention of CMM.
Integrated pathway and epistasis analysis reveals interactive effect of genetic variants at TERF1 and AFAP1L2 loci on melanoma risk.
Authors: Brossard M, Fang S, Vaysse A, Wei Q, Chen WV, Mohamdi H, Maubec E, Lavielle N, Galan P, Lathrop M, Avril MF, Lee JE, Amos CI, Demenais F
Source: Int J Cancer, 2015 Oct 15;137(8), p. 1901-9.
EPub date: 2015 May 26.
Genetic variants in Hippo pathway genes YAP1, TEAD1 and TEAD4 are associated with melanoma-specific survival.
Authors: Yuan H, Liu H, Liu Z, Zhu D, Amos CI, Fang S, Lee JE, Wei Q
Source: Int J Cancer, 2015 Aug 1;137(3), p. 638-45.
EPub date: 2015 Jan 28.
Risk factors for head and neck cancer in young adults: a pooled analysis in the INHANCE consortium.
Authors: Toporcov TN, Znaor A, Zhang ZF, Yu GP, Winn DM, Wei Q, Vilensky M, Vaughan T, Thomson P, Talamini R, Szeszenia-Dabrowska N, Sturgis EM, Smith E, Shangina O, Schwartz SM, Schantz S, Rudnai P, Richiardi L, Ramroth H, Purdue MP, Olshan AF, Eluf-Neto J, Muscat J, Moyses RA, Morgenstern H, Menezes A, McClean M, Matsuo K, Mates D, Macfarlane TV, Lissowska J, Levi F, Lazarus P, La Vecchia C, Lagiou P, Koifman S, Kjaerheim K, Kelsey K, Holcatova I, Herrero R, Healy C, Hayes RB, Franceschi S, Fernandez L, Fabianova E, Daudt AW, Curioni OA, Maso LD, Curado MP, Conway DI, Chen C, Castellsague X, Canova C, Cadoni G, Brennan P, Boccia S, Antunes JL, Ahrens W, Agudo A, Boffetta P, Hashibe M, Lee YC, Filho VW
Source: Int J Epidemiol, 2015 Feb;44(1), p. 169-85.
EPub date: 2015 Jan 22.
Obesity and risk of esophageal adenocarcinoma and Barrett's esophagus: a Mendelian randomization study.
Authors: Thrift AP, Shaheen NJ, Gammon MD, Bernstein L, Reid BJ, Onstad L, Risch HA, Liu G, Bird NC, Wu AH, Corley DA, Romero Y, Chanock SJ, Chow WH, Casson AG, Levine DM, Zhang R, Ek WE, MacGregor S, Ye W, Hardie LJ, Vaughan TL, Whiteman DC
Source: J Natl Cancer Inst, 2014 Nov;106(11), p. null.
EPub date: 2014 Sep 30.
Genetic variants in fanconi anemia pathway genes BRCA2 and FANCA predict melanoma survival.
Authors: Yin J, Liu H, Liu Z, Wang LE, Chen WV, Zhu D, Amos CI, Fang S, Lee JE, Wei Q
Source: J Invest Dermatol, 2015 Feb;135(2), p. 542-50.
EPub date: 2014 Sep 22.
Estimating and explaining the effect of education and income on head and neck cancer risk: INHANCE consortium pooled analysis of 31 case-control studies from 27 countries.
Authors: Conway DI, Brenner DR, McMahon AD, Macpherson LM, Agudo A, Ahrens W, Bosetti C, Brenner H, Castellsague X, Chen C, Curado MP, Curioni OA, Dal Maso L, Daudt AW, de Gois Filho JF, D'Souza G, Edefonti V, Fabianova E, Fernandez L, Franceschi S, Gillison M, Hayes RB, Healy CM, Herrero R, Holcatova I, Jayaprakash V, Kelsey K, Kjaerheim K, Koifman S, La Vecchia C, Lagiou P, Lazarus P, Levi F, Lissowska J, Luce D, Macfarlane TV, Mates D, Matos E, McClean M, Menezes AM, Menvielle G, Merletti F, Morgenstern H, Moysich K, Müller H, Muscat J, Olshan AF, Purdue MP, Ramroth H, Richiardi L, Rudnai P, Schantz S, Schwartz SM, Shangina O, Simonato L, Smith E, Stucker I, Sturgis EM, Szeszenia-Dabrowska N, Talamini R, Thomson P, Vaughan TL, Wei Q, Winn DM, Wunsch-Filho V, Yu GP, Zhang ZF, Zheng T, Znaor A, Boffetta P, Chuang SC, Ghodrat M, Amy Lee YC, Hashibe M, Brennan P
Source: Int J Cancer, 2015 Mar 1;136(5), p. 1125-39.
EPub date: 2014 Aug 23.
4-Nitroquinoline-1-oxide-induced mutagen sensitivity and risk of cutaneous melanoma: a case-control analysis.
Authors: Wang LE, Li C, Xiong P, Gershenwald JE, Prieto VG, Duvic M, Lee JE, Grimm EA, Hsu TC, Wei Q
Source: Melanoma Res, 2014 Jun 27;null, p. null.
EPub date: 2014 Jun 27.
Risk of esophageal adenocarcinoma decreases with height, based on consortium analysis and confirmed by Mendelian randomization.
Authors: Thrift AP, Risch HA, Onstad L, Shaheen NJ, Casson AG, Bernstein L, Corley DA, Levine DM, Chow WH, Reid BJ, Romero Y, Hardie LJ, Liu G, Wu AH, Bird NC, Gammon MD, Ye W, Whiteman DC, Vaughan TL
Source: Clin Gastroenterol Hepatol, 2014 Oct;12(10), p. 1667-76.e1.
EPub date: 2014 Feb 12.
Replication of associations between GWAS SNPs and melanoma risk in the Population Architecture Using Genomics and Epidemiology (PAGE) Study.
Authors: Kocarnik JM, Park SL, Han J, Dumitrescu L, Cheng I, Wilkens LR, Schumacher FR, Kolonel L, Carlson CS, Crawford DC, Goodloe RJ, Dilks H, Baker P, Richardson D, Ambite JL, Song F, Quresh AA, Zhang M, Duggan D, Hutter C, Hindorff LA, Bush WS, Kooperberg C, Le Marchand L, Peters U
Source: J Invest Dermatol, 2014 Jul;134(7), p. 2049-52.
EPub date: 2014 Jan 30.
Association of marijuana smoking with oropharyngeal and oral tongue cancers: pooled analysis from the INHANCE consortium.
Authors: Marks MA, Chaturvedi AK, Kelsey K, Straif K, Berthiller J, Schwartz SM, Smith E, Wyss A, Brennan P, Olshan AF, Wei Q, Sturgis EM, Zhang ZF, Morgenstern H, Muscat J, Lazarus P, McClean M, Chen C, Vaughan TL, Wunsch-Filho V, Curado MP, Koifman S, Matos E, Menezes A, Daudt AW, Fernandez L, Posner M, Boffetta P, Lee YC, Hashibe M, D'Souza G
Source: Cancer Epidemiol Biomarkers Prev, 2014 Jan;23(1), p. 160-71.
EPub date: 2013 Dec 18.
A genome-wide association study identifies new susceptibility loci for esophageal adenocarcinoma and Barrett's esophagus.
Authors: Levine DM, Ek WE, Zhang R, Liu X, Onstad L, Sather C, Lao-Sirieix P, Gammon MD, Corley DA, Shaheen NJ, Bird NC, Hardie LJ, Murray LJ, Reid BJ, Chow WH, Risch HA, Nyrén O, Ye W, Liu G, Romero Y, Bernstein L, Wu AH, Casson AG, Chanock SJ, Harrington P, Caldas I, Debiram-Beecham I, Caldas C, Hayward NK, Pharoah PD, Fitzgerald RC, Macgregor S, Whiteman DC, Vaughan TL
Source: Nat Genet, 2013 Dec;45(12), p. 1487-93.
EPub date: 2013 Oct 13.
Association between a rare novel TP53 variant (rs78378222) and melanoma, squamous cell carcinoma of head and neck and lung cancer susceptibility in non-Hispanic Whites.
Authors: Guan X, Wang LE, Liu Z, Sturgis EM, Wei Q
Source: J Cell Mol Med, 2013 Jul;17(7), p. 873-8.
EPub date: 2013 Jun 7.
Genome-wide association studies identify several new loci associated with pigmentation traits and skin cancer risk in European Americans.
Authors: Zhang M, Song F, Liang L, Nan H, Zhang J, Liu H, Wang LE, Wei Q, Lee JE, Amos CI, Kraft P, Qureshi AA, Han J
Source: Hum Mol Genet, 2013 Jul 15;22(14), p. 2948-59.
EPub date: 2013 Apr 1.
Gene variants in angiogenesis and lymphangiogenesis and cutaneous melanoma progression.
Authors: Park JY, Amankwah EK, Anic GM, Lin HY, Walls B, Park H, Krebs K, Madden M, Maddox K, Marzban S, Fang S, Chen W, Lee JE, Wei Q, Amos CI, Messina JL, Sondak VK, Sellers TA, Egan KM
Source: Cancer Epidemiol Biomarkers Prev, 2013 May;22(5), p. 827-34.
EPub date: 2013 Mar 5.
A variant in FTO shows association with melanoma risk not due to BMI.
Authors: Iles MM, Law MH, Stacey SN, Han J, Fang S, Pfeiffer R, Harland M, Macgregor S, Taylor JC, Aben KK, Akslen LA, Avril MF, Azizi E, Bakker B, Benediktsdottir KR, Bergman W, Scarrà GB, Brown KM, Calista D, Chaudru V, Fargnoli MC, Cust AE, Demenais F, de Waal AC, D?bniak T, Elder DE, Friedman E, Galan P, Ghiorzo P, Gillanders EM, Goldstein AM, Gruis NA, Hansson J, Helsing P, Ho?evar M, Höiom V, Hopper JL, Ingvar C, Janssen M, Jenkins MA, Kanetsky PA, Kiemeney LA, Lang J, Lathrop GM, Leachman S, Lee JE, Lubi?ski J, Mackie RM, Mann GJ, Martin NG, Mayordomo JI, Molven A, Mulder S, Nagore E, Novakovi? S, Okamoto I, Olafsson JH, Olsson H, Pehamberger H, Peris K, Grasa MP, Planelles D, Puig S, Puig-Butille JA, Randerson-Moor J, Requena C, Rivoltini L, Rodolfo M, Santinami M, Sigurgeirsson B, Snowden H, Song F, Sulem P, Thorisdottir K, Tuominen R, Van Belle P, van der Stoep N, van Rossum MM, Wei Q, Wendt J, Zelenika D, Zhang M, Landi MT, Thorleifsson G, Bishop DT, Amos CI, Hayward NK, Stefansson K, Bishop JA, Barrett JH, GenoMEL Consortium, Q-MEGA and AMFS Investigators
Source: Nat Genet, 2013 Apr;45(4), p. 428-32, 432e1.
EPub date: 2013 Mar 3.
Polymorphisms of nucleotide excision repair genes predict melanoma survival.
Authors: Li C, Yin M, Wang LE, Amos CI, Zhu D, Lee JE, Gershenwald JE, Grimm EA, Wei Q
Source: J Invest Dermatol, 2013 Jul;133(7), p. 1813-21.
EPub date: 2013 Feb 14.
Variants in melanocortin 1 receptor gene contribute to risk of melanoma--a direct sequencing analysis in a Texas population.
Authors: Guan X, Niu J, Liu Z, Wang LE, Amos CI, Lee JE, Gershenwald JE, Grimm EA, Wei Q
Source: Pigment Cell Melanoma Res, 2013 May;26(3), p. 422-5.
EPub date: 2013 Feb 19.
Association between putative functional variants in the PSMB9 gene and risk of melanoma--re-analysis of published melanoma genome-wide association studies.
Authors: Qian J, Liu H, Wei S, Liu Z, Li Y, Wang LE, Chen WV, Amos CI, Lee JE, GenoMEL investigators, Iles MM, Law MH, Q-MEGA AMFS investigators, Cust AE, Barrett JH, Montgomery GW, Taylor J, Bishop JA, Macgregor S, Bishop DT, Mann GJ, Hayward NK, Wei Q
Source: Pigment Cell Melanoma Res, 2013 May;26(3), p. 392-401.
EPub date: 2013 Mar 27.
Association between functional polymorphisms in genes involved in the MAPK signaling pathways and cutaneous melanoma risk.
Authors: Liu H, Wang LE, Liu Z, Chen WV, Amos CI, Lee JE, Q-MEGA and AMFS Investigators, GenoMEL Investigators, Iles MM, Law MH, Barrett JH, Montgomery GW, Taylor JC, MacGregor S, Cust AE, Newton Bishop JA, Hayward NK, Bishop DT, Mann GJ, Affleck P, Wei Q
Source: Carcinogenesis, 2013 Apr;34(4), p. 885-92.
EPub date: 2013 Jan 4.
Detectable clonal mosaicism from birth to old age and its relationship to cancer.
Authors: Laurie CC, Laurie CA, Rice K, Doheny KF, Zelnick LR, McHugh CP, Ling H, Hetrick KN, Pugh EW, Amos C, Wei Q, Wang LE, Lee JE, Barnes KC, Hansel NN, Mathias R, Daley D, Beaty TH, Scott AF, Ruczinski I, Scharpf RB, Bierut LJ, Hartz SM, Landi MT, Freedman ND, Goldin LR, Ginsburg D, Li J, Desch KC, Strom SS, Blot WJ, Signorello LB, Ingles SA, Chanock SJ, Berndt SI, Le Marchand L, Henderson BE, Monroe KR, Heit JA, de Andrade M, Armasu SM, Regnier C, Lowe WL, Hayes MG, Marazita ML, Feingold E, Murray JC, Melbye M, Feenstra B, Kang JH, Wiggs JL, Jarvik GP, McDavid AN, Seshan VE, Mirel DB, Crenshaw A, Sharopova N, Wise A, Shen J, Crosslin DR, Levine DM, Zheng X, Udren JI, Bennett S, Nelson SC, Gogarten SM, Conomos MP, Heagerty P, Manolio T, Pasquale LR, Haiman CA, Caporaso N, Weir BS
Source: Nat Genet, 2012 May 6;44(6), p. 642-50.
EPub date: 2012 May 6.
Influence of single nucleotide polymorphisms in the MMP1 promoter region on cutaneous melanoma progression.
Authors: Liu H, Wei Q, Gershenwald JE, Prieto VG, Lee JE, Duvic M, Grimm EA, Wang LE
Source: Melanoma Res, 2012 Apr;22(2), p. 169-75.