Polymorphic genes and gender difference: analysis of a European sample


  • Pieranna Chiarella INAIL-DiMEILA, Roma
  • Pasquale Capone INAIL-DiMEILA, Roma
  • Renata Sisto INAIL-DiMEILA, Roma




gender, susceptibility, gene polymorhpisms, xenobiotics, occupational exposure


Human beings respond in different ways to similar health risks and exposures. Their physiological and genomic variation plausibly contributes to each individual response. Such variability depends on the genotype, inherited from ancestors, as well as on the surrounding environment that shapes the phenotype. Gene polymorphisms are responsible for the phenotypic differences, including not only physical traits but also susceptibility to several diseases as well as in the response to drugs and xenobiotics enocounterd in the daily life. The interest in these genes, referring to those with single nucleotide substitution (SNPs) increased further in the last decades, raising much interest in the field of public health, workplace and demographic studies. In this work we have analyzed a specific number of polymorphic genes involved in detoxification, oxidative stress and repair of DNA damage, to identify potential differences in susceptibility between males and females.


Arizono, K., Osada, Y., Kuroda, Y., 2008. DNA repair gene hOGG1 codon 326 and XRCC1 codon 399 polymorphisms and bladder cancer risk in a Japanese population. Jpn. J. Clin. Oncol., 38 (3), 186-191. https://doi.org/10.1093/jjco/hym176

Baccarelli, A., Calista, D., Minghetti, P., Marinelli, B., Albetti, B., Tseng, T., Hedayati, M., Grossman, L., Landi, G., Struewing, J.P., Landi, M.T., 2004. XPD gene polymorphism and host characteristics in the association with cutaneous malignant melanoma risk. Br. J. Cancer., 90 (2), 497-502. https://doi.org/10.1038/sj.bjc.6601385

Barford, A., Dorling, D., Smith, G.D., Shaw, M., 2006. Life expectancy: women now on top everywhere. BMJ., 332, (7545), 808. https://doi.org/10.1136/bmj.332.7545.808

Berneburg, M., Lehmann, A.R., 2001. Xeroderma pigmentosum and related disorders: defects in DNA repair and transcription. Adv. Genet., 43, 71-102. https://doi.org/10.1016/s0065-2660(01)43004-5

Chiarella, P., Capone, P., Carbonari, D., Sisto, R., 2019. A predictive model assessing genetic susceptibility risk at workplace. Int. J. Environ. Res. Public Health., 16, (11), 2012 https://doi.org/10.3390/ijerph16112012

Chiarella, P., Capone, P., Sisto, R., The role of genetic polymorphisms in the occupational exposure. Chapter book of Intechopen., in The recent topics in genetic polymorphisms. Ed. Çalışkan, M., Erol, O., Oz, G.C., 2019. https://doi.org/10.5772/intechopen.86975

Crimmins, E.M., Shim, H., Zhang, Y.S., Kim, J.K., 2019. Differences between men and women in mortality and the health dimensions of the morbidity process. Clin. Chem., 65 (1), 135-145. https://doi.org/10.1373/clinchem.2018.288332

Ensembl Grch 37, Available online: http://grch37.ensembl.org/Homo_sapiens/Variation (accessed on 05/01/2022).

Faramawy, M.M., Mohammed, T.O., Hossaini, A.M., Kashem, R.A., Abu Rahma, R.M., 2009. Genetic polymorphism of GSTT1 and GSTM1 and susceptibility to chronic obstructive pulmonary disease (COPD). J Crit Care., 24 (3), e7-10. https://doi.org/10.1016/j.jcrc.2009.06.004

Gender gap and accident risk in female workers, “Gender gap e rischio infortunistico al femminile nel nuovo numero di Dati Inail”. Inail report. 10 march 2020 Available online: https://www.inail.it/cs/internet/comunicazione/news-ed-eventi/news/news-dati-inail-donne-2020.html

Haga, H., Yamada, R., Ohnishi, Y., Nakamura, Y., Tanaka, T., 2002. Gene-based SNP discovery as part of the Japanese Millennium Genome Project: identification of 190 562 genetic variations in the human genome. Single-nucleotide polymorphism. J. Hum. Genet., 47 (11), 605-610. https://doi.org/10.1007/s100380200092

Honkura, Y., Matsuo, H., Murakami, S., Sakiyama, M., Mizutari, K., Shiotani, A., Yamamoto, M., Morita, I., Shinomiya, N., Kawase, T., Katori, Y., Motohashi, H., 2016. NRF2 is a key target for prevention of noise-induced hearing loss by reducing oxidative damage of cochlea. Sci. Rep., 6, 19329. https://doi.org/10.1038/srep19329

Hu, Z., Wei, Q., Wang, X., Shen, H., 2004. DNA repair gene XPD polymorphism and lung cancer risk: a meta-analysis. Lung Cancer., 46 (1), 1-10. https://doi.org/10.1016/j.lungcan.2004.03.016

Ishikawa, T., 2014. Genetic polymorphism in the NRF2 gene as a prognosis marker for cancer chemotherapy. Front Genet., 5, 383. https://doi.org/10.3389/fgene.2014.00383

Iyanagi, T., 2007. Molecular Mechanism of Phase I and Phase II Drug‐Metabolizing Enzymes: Implications for Detoxification. Int. Rev. Cytol. 260, 35-112. https://doi.org/10.1016/S0074-7696(06)60002-8

Josephy, P.D., Guengerich, F.P, Miners, J.O., 2005. Phase I and Phase II Drug Metabolism: terminology that we should phase out? Drug Metab. Rev. 37 (4), 575-580. https://doi.org/10.1080/03602530500251220

Jozkowicz, A., Was, H., Dulak, J., 2007. Heme oxygenase-1 in tumors: is it a false friend? Antioxid Redox Signal., 9 (12), 2099-2117. https://doi.org/10.1089/ars.2007.1659

Ku, C.S., Loy, E.Y., Salim, A., Pawitan, Y., Chia, K.S., 2010. The discovery of human genetic variations and their use as disease markers: past, present and future. J. Hum. Genet., 55 (7), 403-415. https://doi.org/10.1038/jhg.2010.55

London, S.J., Lehman, T.A., Taylor, J.A., 1997. Myeloperoxidase genetic polymorphism and lung cancer Risk. Cancer Res. 57 (22), 5001-5003.

Ma, Q., Zhao, Y., Wang, S., Zhang, X., Zhang, J., Du, M., Li, L., Zhang, Y., 2014. Genetic polymorphisms of XRCC3 Thr241Met (C18067T, rs861539) and bladder cancer risk: a meta-analysis of 18 research studies. Tumour Biol. 35, (2), 1473-1480. DOI 10.1007/s13277-013-1203-3.

Mansi, A., Bruni, R., Capone, P., Paci, E., Pigini, D., Simeoni, C., Gnerre, R., Papacchini, M., Tranfo, G., 2012. Toxicol. Lett., 213, (1), 57-62. Low occupational exposure to benzene in a petrochemical plant: modulating effect of genetic polymorphisms and smoking habit on the urinary t,t-MA/SPMA ratio. http://dx.doi.org/10.1016/j.toxlet.2011.02.001

Migliore, L., Nicolì, V., Stoccoro, A., 2021. Gender specific differences in disease susceptibility: The role of epigenetics. Biomedicines., 9 (6), 652. https://doi.org/10.3390/biomedicines9060652

Nebert, D.W., Roe, A.L., Vandale, S.E., Bingham, E., Oakley, G.G., 2002. NAD(P)H:quinone oxidoreductase (NQO1) polymorphism, exposure to benzene, and predisposition to disease: a HuGE review. 4 (2), 62-70. https://doi.org/10.1097/00125817-200203000-00003

Ono, K., Goto, Y., Takagi, S., Baba, S., Tago, N., Nonogi, H., Iway, N., 2004. A promoter variant of the heme oxygenase-1 gene may reduce the incidence of ischemic heart disease in Japanese. Atherosclerosis. 173 (2), 315-319. https://doi.org/10.1016/j.atherosclerosis.2003.11.021

Pace, F, Sciotto, G., 2022. Gender differences in the relationship between work-life balance, career opportunities and general health perception. Sustainability., 14 (1), 357. https://doi.org/10.3390/su14010357

Paolicchi, E., Crea, F., 2011. Italian Society of Pharmacology Newsletter n.35 (Abstract December 2011).

Pizzino, G., Irrera, N., Cucinotta, M.P., Pallio, G., Mannino, F., Arcoraci, V., Squadrito, F., Altavilla, D., Bitto, A., 2017. Oxidative Stress: harms and benefits for human health. Oxid Med Cell Longev., 2017 (3), 8416763. https://doi.org/10.1155/2017/8416763

Poetsch, A.R., 2020. The genomics of oxidative DNA damage, repair, and resulting mutagenesis. Comput. Struct. Biotechnol. J. 18, 207-219. https://doi.org/10.1016/j.csbj.2019.12.013

Reszka, E., Jablonowski, Z., Wieczorek, E., Jablonska, E., Krol, M.B., Gromadzinska, J., Grzegorczyk, A., Sosnowski, M., Wasowicz, W., 2014. Polymorphisms of NRF2 and NRF2 target genes in urinary bladder cancer patients. J. Canc. Res. Clin. Oncol. 140, 1723-1731. https://dx.doi.org/10.1007%2Fs00432-014-1733-0

Sachidanandam, R., Weissman, D., Schmidt, S.C., Kakol, J.M., Stein, L.D., Marth, G., Sherry, S., Mullikin, J.C., Mortimore, B.J., Willey, D.L., Hunt, S.E., Cole, C.G., Coggill, P.C., Rice, C.M., Ning, Z., Rogers, J., Bentley, D.R., Kwok, P.Y., Mardis, E.R., Yeh, R.T., Schultz, B., Cook, L., Davenport, R., Dante, M., Fulton, L., Hillier, L., Waterston, R.H., McPherson, J.D., Gilman, B., Schaffner, S., Van Etten, W.J., Reich, D., Higgins, J., Daly, M.J., Blumenstiel, B., Baldwin, J., Stange-Thomann, N., Zody, M.C., Linton, L., Lander, E.S., Altshuler, D., 2001. A map of human genome sequence variation containing 1.42 million single nucleotide polymorphisms. Nature., 409, (6822), 928-933. https://doi.org/10.1038/35057149

Sánchez, H.B., Finch, C.E., Crimmins, E.M., 2015. Twentieth century surge of excess adult male mortality. Proc Natl Acad Sci USA. 112 (29), 8993-8998. https://doi.org/10.1073/pnas.1421942112

Simeunovic, D., Odanovic, N., Pljesa-Ercegovac, M., Radic, T., Radovanovic, S., Coric, V., Milinkovic, I., Matic, M., Djukic, T., Ristic, A., Risimic, D., Seferovic, P., Simic, T., Simic, D., Savic-Radojevic, A., 2019. Glutathione Transferase P1 polymorphism might be a risk determinant in heart failure. Dis. Markers., 2019, 1-11. https://doi.org/10.1155/2019/6984845

Smart, R.C., Hodgson, E., Molecular and Biochemical Toxicology, ed. Smart, R.C., Hodgson, E., Fifth edition, 2018.

Tranfo, G., Pigini, D., Paci, E., Marini, F., Bonanni, R.C., 2017. Association of exposure to benzene and smoking with oxidative damage to nucleic acids by means of biological monitoring of general population volunteers. Environ Sci Pollut Res., Int., 24 (16), 13885-13894. https://doi.org/10.1007/s11356-016-6366-1

Valavanidis A, Vlachogianni T, Fiotakis C., 2009. 8-hydroxy-2'-deoxyguanosine (8-OHdG): A critical biomarker of oxidative stress and carcinogenesis. J Environ Sci Health C Environ Carcinog Ecotoxicol Rev. 27 (2), 120-139. https://doi.org/10.1080/10590500902885684

Wang. F., Zhao, Q., He, H.R., Zhai, Y.J., Lu, J., Hu, H.B., Zhou, J.S., Yang, Y.H., Li, Y.J., 2015. The association between XRCC1 Arg399Gln polymorphism and risk of leukemia in different populations: a meta-analysis of case-control studies. Onco Targets Ther., 2015 8, 3277-3287. https://doi.org/10.2147/ott.s92752

Woodson, K., Tangrea, J.A., Lehman, T.A., Modali, R., Taylor, K.M., Snyder, K., Taylor, P.R., Virtamo, J., Albanes, D., 2003. Manganese superoxide dismutase (MnSOD) polymorphism, alpha-tocopherol supplementation and prostate cancer risk in the alpha-tocopherol, beta-carotene cancer prevention study (Finland). Cancer Causes & Control., 14 (6), 513-518. https://doi.org/10.1023/a:1024840823328

World health Organization. The global health observatory. Geneva, Switzerland. Available online: https://www.who.int/data/gho/data/themes/mortality-and-global-health-estimates/ghe-leading-causes-of-death (accessed on 3 March 2022)

Zhou, C., Zhou, Y., Li, J., Zhang, Y., Jiang, L., Zeng, X., Feng, X., Wang, Z., 2009. The Arg194Trp polymorphism in the X-ray repair cross-complementing group 1 gene as a potential risk factor of oral cancer: a meta-analysis. Tohoku J Exp Med., 219, (1), 43-51. https://doi.org/10.1620/tjem.219.43

Zou S, Pan X, Hua C., Wu, M., He, B., Chen, Z., 2018. Myeloperoxidase -463 G/A polymorphism is associated with lung cancer risk: A meta-analysis with 7420 cases and 9132 controls. J. Cancer Res., Ther., 14 (9), 282-287. doi: 10.4103/0973-1482.235341.