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Published in: Journal of Occupational Medicine and Toxicology 1/2017

Open Access 01-12-2017 | Research

An etiologic prediction model incorporating biomarkers to predict the bladder cancer risk associated with occupational exposure to aromatic amines: a pilot study

Authors: Giuseppe Mastrangelo, Angela Carta, Cecilia Arici, Sofia Pavanello, Stefano Porru

Published in: Journal of Occupational Medicine and Toxicology | Issue 1/2017

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Abstract

Background

No etiological prediction model incorporating biomarkers is available to predict bladder cancer risk associated with occupational exposure to aromatic amines.

Methods

Cases were 199 bladder cancer patients. Clinical, laboratory and genetic data were predictors in logistic regression models (full and short) in which the dependent variable was 1 for 15 patients with aromatic amines related bladder cancer and 0 otherwise. The receiver operating characteristics approach was adopted; the area under the curve was used to evaluate discriminatory ability of models.

Results

Area under the curve was 0.93 for the full model (including age, smoking and coffee habits, DNA adducts, 12 genotypes) and 0.86 for the short model (including smoking, DNA adducts, 3 genotypes). Using the “best cut-off” of predicted probability of a positive outcome, percentage of cases correctly classified was 92% (full model) against 75% (short model). Cancers classified as “positive outcome” are those to be referred for evaluation by an occupational physician for etiological diagnosis; these patients were 28 (full model) or 60 (short model). Using 3 genotypes instead of 12 can double the number of patients with suspect of aromatic amine related cancer, thus increasing costs of etiologic appraisal.

Conclusions

Integrating clinical, laboratory and genetic factors, we developed the first etiologic prediction model for aromatic amine related bladder cancer. Discriminatory ability was excellent, particularly for the full model, allowing individualized predictions. Validation of our model in external populations is essential for practical use in the clinical setting.
Literature
1.
go back to reference Ferlay J, Parkin DM, Steliarova-Foucher E. Estimates of cancer incidence and mortality in Europe in 2008. Eur J Cancer. 2010;46:765–81.CrossRefPubMed Ferlay J, Parkin DM, Steliarova-Foucher E. Estimates of cancer incidence and mortality in Europe in 2008. Eur J Cancer. 2010;46:765–81.CrossRefPubMed
2.
go back to reference Burger M, Catto JW, Dalbagni G, Grossman HB, Herr H, Karakiewicz P, Kassouf W, Kiemeney LA, La Vecchia C, Shariat S, Lotan Y. Epidemiology and risk factors of urothelial bladder cancer. Eur Urol. 2013;63:234–41.CrossRefPubMed Burger M, Catto JW, Dalbagni G, Grossman HB, Herr H, Karakiewicz P, Kassouf W, Kiemeney LA, La Vecchia C, Shariat S, Lotan Y. Epidemiology and risk factors of urothelial bladder cancer. Eur Urol. 2013;63:234–41.CrossRefPubMed
4.
go back to reference Kogevinas M, Sala M, Boffetta P, Kazerouni N, Kromhout H, Hoar-Zahm S. Cancer risk in the rubber industry: a review of the recent epidemiological evidence. Occup Environ Med. 1998;55:1–12.CrossRefPubMedPubMedCentral Kogevinas M, Sala M, Boffetta P, Kazerouni N, Kromhout H, Hoar-Zahm S. Cancer risk in the rubber industry: a review of the recent epidemiological evidence. Occup Environ Med. 1998;55:1–12.CrossRefPubMedPubMedCentral
5.
go back to reference Baan R, Straif K, Grosse Y, Secretan B, El Ghissassi F, Bouvard V, Benbrahim-Tallaa L, Cogliano V. WHO International Agency for Research on Cancer monograph working group, carcinogenicity of some aromatic amines, organic dyes, and related exposures. Lancet Oncol. 2008;9:322–3.CrossRefPubMed Baan R, Straif K, Grosse Y, Secretan B, El Ghissassi F, Bouvard V, Benbrahim-Tallaa L, Cogliano V. WHO International Agency for Research on Cancer monograph working group, carcinogenicity of some aromatic amines, organic dyes, and related exposures. Lancet Oncol. 2008;9:322–3.CrossRefPubMed
6.
go back to reference Talaska G. Aromatic amines and human urinary bladder cancer: exposure sources and epidemiology. J Environ Sci Health C Environ Carcinog Ecotoxicol Rev. 2003;21:29–43.CrossRefPubMed Talaska G. Aromatic amines and human urinary bladder cancer: exposure sources and epidemiology. J Environ Sci Health C Environ Carcinog Ecotoxicol Rev. 2003;21:29–43.CrossRefPubMed
7.
go back to reference Barone-Adesi F, Richiardi L, Merletti F. Population attributable risk for occupational cancer in Italy. Int J Occup Environ Health. 2005;11:23–31.CrossRefPubMed Barone-Adesi F, Richiardi L, Merletti F. Population attributable risk for occupational cancer in Italy. Int J Occup Environ Health. 2005;11:23–31.CrossRefPubMed
8.
go back to reference Scarselli A, Scano P, Marinaccio A, Iavicoli S. Occupational cancer in Italy: evaluating the extent of compensated cases in the period 1994-2006. Am J Ind Med. 2009;52:859–67.CrossRefPubMed Scarselli A, Scano P, Marinaccio A, Iavicoli S. Occupational cancer in Italy: evaluating the extent of compensated cases in the period 1994-2006. Am J Ind Med. 2009;52:859–67.CrossRefPubMed
9.
go back to reference AIRT Working Group. Italian cancer figures -- report 2006: 1. Incidence, mortality and estimates. Epidemiol Prev. 2006;30(1 Suppl 2):8–10. AIRT Working Group. Italian cancer figures -- report 2006: 1. Incidence, mortality and estimates. Epidemiol Prev. 2006;30(1 Suppl 2):8–10.
11.
go back to reference Pavanello S, Pulliero A, Clonfero E. Influence of GSTM1 null and low repair XPC PAT+ on anti-B[a]PDE-DNA adduct in mononuclear white blood cells of subjects low exposed to PAHs through smoking and diet. Mutat Res. 2008;638:195–204.CrossRefPubMed Pavanello S, Pulliero A, Clonfero E. Influence of GSTM1 null and low repair XPC PAT+ on anti-B[a]PDE-DNA adduct in mononuclear white blood cells of subjects low exposed to PAHs through smoking and diet. Mutat Res. 2008;638:195–204.CrossRefPubMed
12.
go back to reference Lotan Y, Svatek RS, Krabbe LM, Xylinas E, Klatte T, Shariat SF. Prospective external validation of a bladder cancer detection model. J Urol. 2014;192:1343–8. Lotan Y, Svatek RS, Krabbe LM, Xylinas E, Klatte T, Shariat SF. Prospective external validation of a bladder cancer detection model. J Urol. 2014;192:1343–8.
13.
go back to reference Kluth LA, Black PC, Bochner BH, Catto J, Lerner SP, Stenzl A, Sylvester R, Vickers AJ, Xylinas E, Shariat SF. Prognostic and prediction tools in bladder cancer: a comprehensive review of the literature. Eur Urol. 2015;68:238–53.CrossRefPubMed Kluth LA, Black PC, Bochner BH, Catto J, Lerner SP, Stenzl A, Sylvester R, Vickers AJ, Xylinas E, Shariat SF. Prognostic and prediction tools in bladder cancer: a comprehensive review of the literature. Eur Urol. 2015;68:238–53.CrossRefPubMed
14.
go back to reference Terracciano D, Ferro M, Terreri S, Lucarelli G, D'Elia C, Musi G, de Cobelli O, Mirone V, Cimmino A. Urinary long noncoding RNAs in nonmuscle-invasive bladder cancer: new architects in cancer prognostic biomarkers. Transl Res. 2017;184:108–17.CrossRefPubMed Terracciano D, Ferro M, Terreri S, Lucarelli G, D'Elia C, Musi G, de Cobelli O, Mirone V, Cimmino A. Urinary long noncoding RNAs in nonmuscle-invasive bladder cancer: new architects in cancer prognostic biomarkers. Transl Res. 2017;184:108–17.CrossRefPubMed
15.
go back to reference Terreri S, Durso M, Colonna V, Romanelli A, Terracciano D, Ferro M, Perdonà S, Castaldo L, Febbraio F, de Nigris F, Cimmino A. New Cross-Talk Layer between Ultraconserved Non-Coding RNAs, MicroRNAs and Polycomb Protein YY1 in Bladder Cancer. Genes (Basel). 2016;7:127. Terreri S, Durso M, Colonna V, Romanelli A, Terracciano D, Ferro M, Perdonà S, Castaldo L, Febbraio F, de Nigris F, Cimmino A. New Cross-Talk Layer between Ultraconserved Non-Coding RNAs, MicroRNAs and Polycomb Protein YY1 in Bladder Cancer. Genes (Basel). 2016;7:127.
16.
go back to reference Olivieri M, Ferro M, Terreri S, Durso M, Romanelli A, Avitabile C, De Cobelli O, Messere A, Bruzzese D, Vannini I, Marinelli L, Novellino E, Zhang W, Incoronato M, Ilardi G, Staibano S, Marra L, Franco R, Perdonà S, Terracciano D, Czerniak B, Liguori GL, Colonna V, Fabbri M, Febbraio F, Calin GA, Cimmino A. Long non-coding RNA containing ultraconserved genomic region 8 promotes bladder cancer tumorigenesis. Oncotarget. 2016;7:20636–54. Olivieri M, Ferro M, Terreri S, Durso M, Romanelli A, Avitabile C, De Cobelli O, Messere A, Bruzzese D, Vannini I, Marinelli L, Novellino E, Zhang W, Incoronato M, Ilardi G, Staibano S, Marra L, Franco R, Perdonà S, Terracciano D, Czerniak B, Liguori GL, Colonna V, Fabbri M, Febbraio F, Calin GA, Cimmino A. Long non-coding RNA containing ultraconserved genomic region 8 promotes bladder cancer tumorigenesis. Oncotarget. 2016;7:20636–54.
17.
go back to reference Shen M, Hung RJ, Brennan P, Malaveille C, Donato F, Placidi D, Carta A, Hautefeuille A, Boffetta P, Porru S. Polymorphisms of the DNA repair genes XRCC1, XRCC3, XPD, interaction with environmental exposures, and bladder cancer risk in a case–control study in northern Italy. Cancer Epidemiol Biomark Prev. 2003;12:1234–40. Shen M, Hung RJ, Brennan P, Malaveille C, Donato F, Placidi D, Carta A, Hautefeuille A, Boffetta P, Porru S. Polymorphisms of the DNA repair genes XRCC1, XRCC3, XPD, interaction with environmental exposures, and bladder cancer risk in a case–control study in northern Italy. Cancer Epidemiol Biomark Prev. 2003;12:1234–40.
18.
go back to reference Covolo L, Placidi D, Gelatti U, Carta A, Scotto Di Carlo A, Lodetti P, Piccichè A, Orizio G, Campagna M, Arici C, Porru S. Bladder cancer, GSTs, NAT1, NAT2, SULT1A1, XRCC1, XRCC3, XPD genetic polymorphisms and coffee consumption: a case-control study. Eur J Epidemiol. 2008;23:355–62.CrossRefPubMed Covolo L, Placidi D, Gelatti U, Carta A, Scotto Di Carlo A, Lodetti P, Piccichè A, Orizio G, Campagna M, Arici C, Porru S. Bladder cancer, GSTs, NAT1, NAT2, SULT1A1, XRCC1, XRCC3, XPD genetic polymorphisms and coffee consumption: a case-control study. Eur J Epidemiol. 2008;23:355–62.CrossRefPubMed
19.
go back to reference Pavanello S, Mastrangelo G, Placidi D, Campagna M, Pulliero A, Carta A, Arici C, Porru S. CYP1A2 polymorphisms, occupational and environmental exposures and risk of bladder cancer. Eur J Epidemiol. 2010;25:491–500.CrossRefPubMed Pavanello S, Mastrangelo G, Placidi D, Campagna M, Pulliero A, Carta A, Arici C, Porru S. CYP1A2 polymorphisms, occupational and environmental exposures and risk of bladder cancer. Eur J Epidemiol. 2010;25:491–500.CrossRefPubMed
20.
go back to reference Porru S, Pavanello S, Carta A, Arici C, Simeone C, Izzotti A, Mastrangelo G. Complex relationships between occupation, environment, DNA adducts, genetic polymorphisms and bladder cancer in a case-control study using a structural equation modeling. PLoS One. 2014;9(4):e94566.CrossRefPubMedPubMedCentral Porru S, Pavanello S, Carta A, Arici C, Simeone C, Izzotti A, Mastrangelo G. Complex relationships between occupation, environment, DNA adducts, genetic polymorphisms and bladder cancer in a case-control study using a structural equation modeling. PLoS One. 2014;9(4):e94566.CrossRefPubMedPubMedCentral
21.
go back to reference Porru S, Placidi D, Carta A, Gelatti U, Ribero ML, Tagger A, Boffetta P, Donato F. Primary liver cancer and occupation in men: a case-control study in high-incidence area in northern Italy. Int J Cancer. 2001;94:878–83.CrossRefPubMed Porru S, Placidi D, Carta A, Gelatti U, Ribero ML, Tagger A, Boffetta P, Donato F. Primary liver cancer and occupation in men: a case-control study in high-incidence area in northern Italy. Int J Cancer. 2001;94:878–83.CrossRefPubMed
22.
go back to reference Coggon D, Martyn C, Palmer KT, Evanoff B. Assessing case definitions in the absence of a diagnostic gold standard. Int J Epidemiol. 2005;34:949–52.CrossRefPubMed Coggon D, Martyn C, Palmer KT, Evanoff B. Assessing case definitions in the absence of a diagnostic gold standard. Int J Epidemiol. 2005;34:949–52.CrossRefPubMed
23.
go back to reference Pira E, Piolatto G, Negri E, Romano C, Boffetta P, Lipworth L, McLaughlin JK, La Vecchia C. Bladder cancer mortality of workers exposed to aromatic amines: a 58-year follow-up. J Natl Cancer Inst. 2010;102:1096–9.CrossRefPubMed Pira E, Piolatto G, Negri E, Romano C, Boffetta P, Lipworth L, McLaughlin JK, La Vecchia C. Bladder cancer mortality of workers exposed to aromatic amines: a 58-year follow-up. J Natl Cancer Inst. 2010;102:1096–9.CrossRefPubMed
24.
go back to reference Miyakawa M, Tachibana M, Miyakawa A, Yoshida K, Shimada N, Murai M, Kondo T. Re-evaluation of the latent period of bladder cancer in dyestuff-plant workers in Japan. Int J Urol. 2001;8:423–30.CrossRefPubMed Miyakawa M, Tachibana M, Miyakawa A, Yoshida K, Shimada N, Murai M, Kondo T. Re-evaluation of the latent period of bladder cancer in dyestuff-plant workers in Japan. Int J Urol. 2001;8:423–30.CrossRefPubMed
25.
go back to reference Swets JA. Measuring the accuracy of diagnostic systems. Science. 1998;240:1285–93.CrossRef Swets JA. Measuring the accuracy of diagnostic systems. Science. 1998;240:1285–93.CrossRef
28.
go back to reference Vickers AJ, Calster BV, Steyerberg EW. Net benefit approaches to the evaluation of prediction models, molecular markers, and diagnostic tests. BMJ. 2016;352:i6.CrossRefPubMedPubMedCentral Vickers AJ, Calster BV, Steyerberg EW. Net benefit approaches to the evaluation of prediction models, molecular markers, and diagnostic tests. BMJ. 2016;352:i6.CrossRefPubMedPubMedCentral
29.
go back to reference Kerr KF, Brown MD, Zhu K, Janes H. Assessing the clinical impact of risk prediction models with decision curves: guidance for correct interpretation and appropriate use. J Clin Oncol. 2016;34:2534–40.CrossRefPubMedPubMedCentral Kerr KF, Brown MD, Zhu K, Janes H. Assessing the clinical impact of risk prediction models with decision curves: guidance for correct interpretation and appropriate use. J Clin Oncol. 2016;34:2534–40.CrossRefPubMedPubMedCentral
30.
go back to reference Demidenko E. Sample size and optimal design for logistic regression with binary interaction. Stat Med. 2008;27:36–46.CrossRefPubMed Demidenko E. Sample size and optimal design for logistic regression with binary interaction. Stat Med. 2008;27:36–46.CrossRefPubMed
31.
go back to reference Armitage P. Statistical methods in medical research. 1st ed. Oxford: Blackwell Science; 1971. Armitage P. Statistical methods in medical research. 1st ed. Oxford: Blackwell Science; 1971.
32.
go back to reference Fan ZJ, Bonauto DK, Foley MP, Silverstein BA. Underreporting of work-related injury or illness to workers’ compensation: individual and industry factors. J Occup Environ Med. 2006;48:914–22.CrossRefPubMed Fan ZJ, Bonauto DK, Foley MP, Silverstein BA. Underreporting of work-related injury or illness to workers’ compensation: individual and industry factors. J Occup Environ Med. 2006;48:914–22.CrossRefPubMed
Metadata
Title
An etiologic prediction model incorporating biomarkers to predict the bladder cancer risk associated with occupational exposure to aromatic amines: a pilot study
Authors
Giuseppe Mastrangelo
Angela Carta
Cecilia Arici
Sofia Pavanello
Stefano Porru
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Journal of Occupational Medicine and Toxicology / Issue 1/2017
Electronic ISSN: 1745-6673
DOI
https://doi.org/10.1186/s12995-017-0167-4

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