|Grant Number:||7R01CA102484-04 Interpret this number|
|Primary Investigator:||Ahsan, Habibul|
|Organization:||University Of Chicago|
|Project Title:||Genetic Susceptibility to Arsenic-Induced Skin Cancer|
Between 30 and 50 million people in Bangladesh have been chronically exposed to high levels of arsenic, a class I human carcinogen, through contaminated drinking water. Although not clearly understood, based on current evidence, arsenic most likely exerts its carcinogenic effect through oxidative stress mediated DNA damage. While skin cancer and its precursor lesions are the most common arsenic-related conditions, there are wide variations in risk. We propose to examine the novel hypotheses that variants in the oxidative stress genes involved in arsenic-induced oxidative DNA damage and in DNA repair genes involved in the repair of this damage, are related to the risk of skin cancers and their precursor skin lesions, either independently or by modifying the effects of arsenic and these effects may be influenced by host antioxidant status measured by serum carotenoids, tocopherol and selenium. These hypotheses are supported by our strong preliminary data. Using existing resources (stored genomic DNA and comprehensive arsenic exposure and clinical data) from our ongoing prospective cohort study of 12,000 individuals, we propose to examine our hypotheses through a series of case-control and case-cohort analyses among 1,200 already identified skin lesions cases, 400 yet-to-be diagnosed skin cancer cases and 1,200 already identified random cohort members as controls. We will genotype the skin lesion, skin cancer and control subjects for 13 polymorphisms in the 4 oxidative stress genes (MPO, CAT, MnSOD, and GPX) and 6 DNA repair genes (OGG1, XPD, XRCC1, XRCC3, LIG1 and LIG4) using the high-throughput FP-TDI method established in our laboratory. The effect of the polymorphisms on arsenic-induced skin cancers and premalignant skin lesions, both independently and jointly with arsenic exposure, will be evaluated by estimating relatives risks from Cox's proportional hazards regression models. The proposed study is the first to investigate these novel hypotheses and has several scientific, methodological, logistic and practical strengths. Data generated will have implications not only for the massive public health issue relevant for millions of people in an underdeveloped country but also for arsenic exposed populations in other countries, including the US.
Arsenic metabolism efficiency has a causal role in arsenic toxicity: Mendelian randomization and gene-environment interaction.
Authors: Pierce BL, Tong L, Argos M, Gao J, Farzana J, Roy S, Paul-Brutus R, Rahaman R, Rakibuz-Zaman M, Parvez F, Ahmed A, Quasem I, Hore SK, Alam S, Islam T, Harjes J, Sarwar G, Slavkovich V, Gamble MV, Chen Y, Yunus M, Rahman M, Baron JA, Graziano JH, Ahsan H
Source: Int J Epidemiol, 2013 Dec;42(6), p. 1862-71.
Association between body mass index and cardiovascular disease mortality in east Asians and south Asians: pooled analysis of prospective data from the Asia Cohort Consortium.
Authors: Chen Y, Copeland WK, Vedanthan R, Grant E, Lee JE, Gu D, Gupta PC, Ramadas K, Inoue M, Tsugane S, Tamakoshi A, Gao YT, Yuan JM, Shu XO, Ozasa K, Tsuji I, Kakizaki M, Tanaka H, Nishino Y, Chen CJ, Wang R, Yoo KY, Ahn YO, Ahsan H, Pan WH, Chen CS, Pednekar MS, Sauvaget C, Sasazuki S, Yang G, Koh WP, Xiang YB, Ohishi W, Watanabe T, Sugawara Y, Matsuo K, You SL, Park SK, Kim DH, Parvez F, Chuang SY, Ge W, Rolland B, McLerran D, Sinha R, Thornquist M, Kang D, Feng Z, Boffetta P, Zheng W, He J, Potter JD
Source: BMJ, 2013 Oct 1;347, p. f5446.
EPub date: 2013 Oct 1.
Meat intake and cause-specific mortality: a pooled analysis of Asian prospective cohort studies.
Authors: Lee JE, McLerran DF, Rolland B, Chen Y, Grant EJ, Vedanthan R, Inoue M, Tsugane S, Gao YT, Tsuji I, Kakizaki M, Ahsan H, Ahn YO, Pan WH, Ozasa K, Yoo KY, Sasazuki S, Yang G, Watanabe T, Sugawara Y, Parvez F, Kim DH, Chuang SY, Ohishi W, Park SK, Feng Z, Thornquist M, Boffetta P, Zheng W, Kang D, Potter J, Sinha R
Source: Am J Clin Nutr, 2013 Oct;98(4), p. 1032-41.
EPub date: 2013 Jul 31.
The broad scope of health effects from chronic arsenic exposure: update on a worldwide public health problem.
Authors: Naujokas MF, Anderson B, Ahsan H, Aposhian HV, Graziano JH, Thompson C, Suk WA
Source: Environ Health Perspect, 2013 Mar;121(3), p. 295-302.
EPub date: 2012 Dec 21.
Arsenic exposure and oral cavity lesions in Bangladesh.
Authors: Syed EH, Melkonian S, Poudel KC, Yasuoka J, Otsuka K, Ahmed A, Islam T, Parvez F, Slavkovich V, Graziano JH, Ahsan H, Jimba M
Source: J Occup Environ Med, 2013 Jan;55(1), p. 59-66.
Association of body mass index and risk of death from pancreatic cancer in Asians: findings from the Asia Cohort Consortium.
Authors: Lin Y, Fu R, Grant E, Chen Y, Lee JE, Gupta PC, Ramadas K, Inoue M, Tsugane S, Gao YT, Tamakoshi A, Shu XO, Ozasa K, Tsuji I, Kakizaki M, Tanaka H, Chen CJ, Yoo KY, Ahn YO, Ahsan H, Pednekar MS, Sauvaget C, Sasazuki S, Yang G, Xiang YB, Ohishi W, Watanabe T, Nishino Y, Matsuo K, You SL, Park SK, Kim DH, Parvez F, Rolland B, McLerran D, Sinha R, Boffetta P, Zheng W, Thornquist M, Feng Z, Kang D, Potter JD
Source: Eur J Cancer Prev, 2013 May;22(3), p. 244-50.
Better cancer biomarker discovery through better study design.
Authors: Rundle A, Ahsan H, Vineis P
Source: Eur J Clin Invest, 2012 Dec;42(12), p. 1350-9.
EPub date: 2012 Sep 23.
Unidentified genetic variants influence pancreatic cancer risk: an analysis of polygenic susceptibility in the PanScan study.
Authors: Pierce BL, Tong L, Kraft P, Ahsan H
Source: Genet Epidemiol, 2012 Jul;36(5), p. 517-24.
EPub date: 2012 May 29.
Prospective investigation of major dietary patterns and risk of cardiovascular mortality in Bangladesh.
Authors: Chen Y, McClintock TR, Segers S, Parvez F, Islam T, Ahmed A, Rakibuz-Zaman M, Hasan R, Sarwar G, Ahsan H
Source: Int J Cardiol, 2013 Aug 20;167(4), p. 1495-501.
EPub date: 2012 May 4.
Genome-wide association study identifies chromosome 10q24.32 variants associated with arsenic metabolism and toxicity phenotypes in Bangladesh.
Authors: Pierce BL, Kibriya MG, Tong L, Jasmine F, Argos M, Roy S, Paul-Brutus R, Rahaman R, Rakibuz-Zaman M, Parvez F, Ahmed A, Quasem I, Hore SK, Alam S, Islam T, Slavkovich V, Gamble MV, Yunus M, Rahman M, Baron JA, Graziano JH, Ahsan H
Source: PLoS Genet, 2012;8(2), p. e1002522.
EPub date: 2012 Feb 23.
A genome-wide study of cytogenetic changes in colorectal cancer using SNP microarrays: opportunities for future personalized treatment.
Authors: Jasmine F, Rahaman R, Dodsworth C, Roy S, Paul R, Raza M, Paul-Brutus R, Kamal M, Ahsan H, Kibriya MG
Source: PLoS One, 2012;7(2), p. e31968.
EPub date: 2012 Feb 20.
Interpretation of genome-wide infinium methylation data from ligated DNA in formalin-fixed, paraffin-embedded paired tumor and normal tissue.
Authors: Jasmine F, Rahaman R, Roy S, Raza M, Paul R, Rakibuz-Zaman M, Paul-Brutus R, Dodsworth C, Kamal M, Ahsan H, Kibriya MG
Source: BMC Res Notes, 2012 Feb 22;5, p. 117.
EPub date: 2012 Feb 22.
Betel quid chewing in rural Bangladesh: prevalence, predictors and relationship to blood pressure.
Authors: Heck JE, Marcotte EL, Argos M, Parvez F, Ahmed A, Islam T, Sarwar G, Hasan R, Ahsan H, Chen Y
Source: Int J Epidemiol, 2012 Apr;41(2), p. 462-71.
EPub date: 2011 Dec 25.
Body mass, tobacco smoking, alcohol drinking and risk of cancer of the small intestine--a pooled analysis of over 500,000 subjects in the Asia Cohort Consortium.
Authors: Boffetta P, Hazelton WD, Chen Y, Sinha R, Inoue M, Gao YT, Koh WP, Shu XO, Grant EJ, Tsuji I, Nishino Y, You SL, Yoo KY, Yuan JM, Kim J, Tsugane S, Yang G, Wang R, Xiang YB, Ozasa K, Nagai M, Kakizaki M, Chen CJ, Park SK, Shin A, Ahsan H, Qu CX, Lee JE, Thornquist M, Rolland B, Feng Z, Zheng W, Potter JD
Source: Ann Oncol, 2012 Jul;23(7), p. 1894-8.
EPub date: 2011 Dec 6.
Arsenic exposure from drinking water and dyspnoea risk in Araihazar, Bangladesh: a population-based study.
Authors: Pesola GR, Parvez F, Chen Y, Ahmed A, Hasan R, Ahsan H
Source: Eur Respir J, 2012 May;39(5), p. 1076-83.
EPub date: 2011 Nov 16.
Body mass index and diabetes in Asia: a cross-sectional pooled analysis of 900,000 individuals in the Asia cohort consortium.
Authors: Boffetta P, McLerran D, Chen Y, Inoue M, Sinha R, He J, Gupta PC, Tsugane S, Irie F, Tamakoshi A, Gao YT, Shu XO, Wang R, Tsuji I, Kuriyama S, Matsuo K, Satoh H, Chen CJ, Yuan JM, Yoo KY, Ahsan H, Pan WH, Gu D, Pednekar MS, Sasazuki S, Sairenchi T, Yang G, Xiang YB, Nagai M, Tanaka H, Nishino Y, You SL, Koh WP, Park SK, Shen CY, Thornquist M, Kang D, Rolland B, Feng Z, Zheng W, Potter JD
Source: PLoS One, 2011;6(6), p. e19930.
EPub date: 2011 Jun 22.
A genome-wide DNA methylation study in colorectal carcinoma.
Authors: Kibriya MG, Raza M, Jasmine F, Roy S, Paul-Brutus R, Rahaman R, Dodsworth C, Rakibuz-Zaman M, Kamal M, Ahsan H
Source: BMC Med Genomics, 2011 Jun 23;4, p. 50.
EPub date: 2011 Jun 23.
Late-onset asymmetric myoclonus: an emerging syndrome.
Authors: Katschnig P, Massano J, Edwards MJ, Schwingenschuh P, Cordivari C, Bhatia KP
Source: Mov Disord, 2011 Aug 1;26(9), p. 1744-8.
EPub date: 2011 May 26.
A prospective study of arsenic exposure from drinking water and incidence of skin lesions in Bangladesh.
Authors: Argos M, Kalra T, Pierce BL, Chen Y, Parvez F, Islam T, Ahmed A, Hasan R, Hasan K, Sarwar G, Levy D, Slavkovich V, Graziano JH, Rathouz PJ, Ahsan H
Source: Am J Epidemiol, 2011 Jul 15;174(2), p. 185-94.
EPub date: 2011 May 16.
Arsenic exposure from drinking water and mortality from cardiovascular disease in Bangladesh: prospective cohort study.
Authors: Chen Y, Graziano JH, Parvez F, Liu M, Slavkovich V, Kalra T, Argos M, Islam T, Ahmed A, Rakibuz-Zaman M, Hasan R, Sarwar G, Levy D, van Geen A, Ahsan H
Source: BMJ, 2011 May 5;342, p. d2431.
EPub date: 2011 May 5.