DOI QR코드

DOI QR Code

Sex Differences in Cancer: Epidemiology, Genetics and Therapy

  • Kim, Hae-In (Duksung Innovative Drug Center, College of Pharmacy, Duksung Women's University) ;
  • Lim, Hyesol (Duksung Innovative Drug Center, College of Pharmacy, Duksung Women's University) ;
  • Moon, Aree (Duksung Innovative Drug Center, College of Pharmacy, Duksung Women's University)
  • Received : 2018.06.01
  • Accepted : 2018.06.07
  • Published : 2018.07.01

Abstract

The incidence and mortality of various cancers are associated with sex-specific disparities. Sex differences in cancer epidemiology are one of the most significant findings. Men are more prone to die from cancer, particularly hematological malignancies. Sex difference in cancer incidence is attributed to regulation at the genetic/molecular level and sex hormones such as estrogen. At the genetic/molecular level, gene polymorphism and altered enzymes involving drug metabolism generate differences in cancer incidence between men and women. Sex hormones modulate gene expression in various cancers. Genetic or hormonal differences between men and women determine the effect of chemotherapy. Until today, animal studies and clinical trials investigating chemotherapy showed sex imbalance. Chemotherapy has been used without consideration of sex differences, resulting in disparity of efficacy and toxicity between sexes. Based on accumulating evidence supporting sex differences in chemotherapy, all clinical trials in cancer must incorporate sex differences for a better understanding of biological differences between men and women. In the present review, we summarized the sex differences in (1) incidence and mortality of cancer, (2) genetic and molecular basis of cancer, (3) sex hormones in cancer incidence, and (4) efficacy and toxicity of chemotherapy. This review provides useful information for sex-based chemotherapy and development of personalized therapeutic strategies against cancer.

Keywords

Acknowledgement

Supported by : Duksung Women's University

References

  1. Anderson, G. D. (2005) Sex and racial differences in pharmacological response: where is the evidence? Pharmacogenetics, pharmacokinetics, and pharmacodynamics. J. Womens Health (Larchmt) 14, 19-29. https://doi.org/10.1089/jwh.2005.14.19
  2. Arand, M., Muhlbauer, R., Hengstler, J., Jager, E., Fuchs, J., Winkler, L. and Oesch, F. (1996) A multiplex polymerase chain reaction protocol for the simultaneous analysis of the glutathione S-transferase GSTM1 and GSTT1 polymorphisms. Anal. Biochem. 236, 184-186. https://doi.org/10.1006/abio.1996.0153
  3. Arnold, M., Sierra, M. S., Laversanne, M., Soerjomataram, I., Jemal, A. and Bray, F. (2017) Global patterns and trends in colorectal cancer incidence and mortality. Gut 66, 683-691. https://doi.org/10.1136/gutjnl-2015-310912
  4. Asher, G., Lotem, J., Kama, R., Sachs, L. and Shaul, Y. (2002) NQO1 stabilizes p53 through a distinct pathway. Proc. Natl. Acad. Sci. U.S.A. 99, 3099-3104.
  5. Becker, J. B., Arnold, A. P., Berkley, K. J., Blaustein, J. D., Eckel, L. A., Hampson, E., Herman, J. P., Marts, S., Sadee, W., Steiner, M., Taylor, J. and Young, E. (2005) Strategies and methods for research on sex differences in brain and behavior. Endocrinology 146, 1650-1673. https://doi.org/10.1210/en.2004-1142
  6. Bellon, S. F., Coleman, J. H. and Lippard, S. J. (1991) DNA unwinding produced by site-specific intrastrand cross-links of the antitumor drug cis-diamminedichloroplatinum (II). Biochemistry 30, 8026-8035. https://doi.org/10.1021/bi00246a021
  7. Bertuccio, P., Chatenoud, L., Levi, F., Praud, D., Ferlay, J., Negri, E., Malvezzi, M. and La Vecchia, C. (2009) Recent patterns in gastric cancer: a global overview. Int. J. Cancer 125, 666-673. https://doi.org/10.1002/ijc.24290
  8. Bond, G. L., Hu, W., Bond, E. E., Robins, H., Lutzker, S. G., Arva, N. C., Bargonetti, J., Bartel, F., Taubert, H., Wuerl, P., Onel, K., Yip, L., Hwang, S. J., Strong, L. C., Lozano, G. and Levine, A. J. (2004) A single nucleotide polymorphism in the MDM2 promoter attenuates the p53 tumor suppressor pathway and accelerates tumor formation in humans. Cell 119, 591-602. https://doi.org/10.1016/j.cell.2004.11.022
  9. Bond, G. L., Hirshfield, K. M., Kirchhoff, T., Alexe, G., Bond, E. E., Robins, H., Bartel, F., Taubert, H., Wuerl, P., Hait, W., Toppmeyer, D., Offit, K. and Levine, A. J. (2006) MDM2 SNP309 accelerates tumor formation in a gender-specific and hormone-dependent manner. Cancer Res. 66, 5104-5110. https://doi.org/10.1158/0008-5472.CAN-06-0180
  10. Bolufer, P., Collado, M., Barragan, E., Cervera, J., Calasanz, M. J., Colomer, D., Roman-Gomez, J. and Sanz, M. A. (2007) The potential effect of gender in combination with common genetic polymorphisms of drug-metabolizing enzymes on the risk of developing acute leukemia. Haematologica 92, 308-314. https://doi.org/10.3324/haematol.10752
  11. Brahmer, J. R., Dahlberg, S. E., Gray, R. J., Schiller, J. H., Perry, M. C., Sandler, A. and Johnson, D. H. (2011) Sex differences in outcome with bevacizumab therapy: analysis of patients with advanced-stage non-small cell lung cancer treated with or without bevacizumab in combination with paclitaxel and carboplatin in the Eastern Cooperative Oncology Group Trial 4599. J. Thorac. Oncol. 6, 103-108.
  12. Bren, L. (2005) Does sex make a difference? F.D.A. Consum. 39, 10-15.
  13. Cho, H. J., Eom, H. S., Kim, H. J., Kim, I. S., Lee, G. W. and Kong, S. Y. (2010) Glutathione-S-transferase genotypes influence the risk of chemotherapy-related toxicities and prognosis in Korean patients with diffuse large B-cell lymphoma. Cancer Genet. Cytogenet 198, 40-46. https://doi.org/10.1016/j.cancergencyto.2009.12.004
  14. Crocetti, E., Mallone, S., Robsahm, T. E., Gavin, A., Agius, D., Ardanaz, E., Lopez, M. C., Innos, K., Minicozzi, P., Borgognoni, L., Pierannunzio, D., Eisemann, N. and EUROCARE-5 Working Group (2015) Survival of patients with skin melanoma in Europe increases further: results of the EUROCARE-5 study. Eur. J. Cancer 51, 2179-2190. https://doi.org/10.1016/j.ejca.2015.07.039
  15. Diasio, R. B. and Harris, B. E. (1989) Clinical pharmacology of 5-fluorouracil. Clin. Pharmacokinet. 16, 215-237. https://doi.org/10.2165/00003088-198916040-00002
  16. Do, T. N., Ucisik-Akkaya, E., Davis, C. F., Morrison, B. A. and Dorak, M. T. (2010) An intronic polymorphism of IRF4 gene influences gene transcription in vitro and shows a risk association with childhood acute lymphoblastic leukemia in males. Biochim. Biophys. Acta 1802, 292-300. https://doi.org/10.1016/j.bbadis.2009.10.015
  17. Dobbs, N. A., Twelves, C. J., Gillies, H., James, C. A., Harper, P. G. and Rubens, R. D. (1995) Gender affects doxorubicin pharmacokinetics in patients with normal liver biochemistry. Cancer Chemother. Pharmacol. 36, 473-476. https://doi.org/10.1007/BF00685796
  18. Dorak, M. T. and Karpuzoglu, E. (2012) Gender differences in cancer susceptibility: an inadequately addressed issue. Front Genet. 3, 268.
  19. Eliyahu, D., Michalovitz, D., Eliyahu, S., Pinhasi-Kimhi, O. and Oren, M. (1989) Wild-type p53 can inhibit oncogene-mediated focus formation. Proc. Natl. Acad. Sci. U.S.A. 86, 8763-8767. https://doi.org/10.1073/pnas.86.22.8763
  20. Etienne, M. C., Lagrange, J. L., Dassonville, O., Fleming, R., Thyss, A., Renee, N., Schneider, M., Demard, F. and Milano, G. (1994) Population study of dihydropyrimidine dehydrogenase in cancer patients. J. Clin. Oncol. 12, 2248-2253. https://doi.org/10.1200/JCO.1994.12.11.2248
  21. Everson, G. T., McKinley, C. and Kern, F., Jr. (1991) Mechanisms of gallstone formation in women. Effects of exogenous estrogen (Premarin) and dietary cholesterol on hepatic lipid metabolism. J. Clin. Invest. 87, 237-246. https://doi.org/10.1172/JCI114977
  22. Fagerholm, R., Hofstetter, B., Tommiska, J., Aaltonen, K., Vrtel, R., Syrjakoski, K., Kallioniemi, A., Kilpivaara, O., Mannermaa, A., Kosma, V. M., Uusitupa, M., Eskelinen, M., Kataja, V., Aittomaki, K., von Smitten, K., Heikkila, P., Lukas, J., Holli, K., Bartkova, J., Blomqvist, C., Bartek, J. and Nevanlinna, H. (2008) NAD(P)H:quinone oxidoreductase 1 NQO1*2 genotype (P187S) is a strong prognostic and predictive factor in breast cancer. Nat. Genet. 40, 844-853. https://doi.org/10.1038/ng.155
  23. Farhana, L., Nangia-Makker, P., Arbit, E., Shango, K., Sarkar, S., Mahmud, H., Hadden, T., Yu, Y. and Majumdar, A. P. (2016) Bile acid: a potential inducer of colon cancer stem cells. Stem Cell Res. Ther. 7, 181. https://doi.org/10.1186/s13287-016-0439-4
  24. Ferrara, N. (2004) Vascular endothelial growth factor: basic science and clinical progress. Endocr. Rev. 25, 581-611. https://doi.org/10.1210/er.2003-0027
  25. Fitzmaurice, C., Allen, C., Barber, R. M., Barregard, L., Bhutta, Z. A., Brenner, H., Dicker, D. J., Chimed-Orchir, O., Dandona, R., Dandona, L., Fleming, T., Forouzanfar, M. H., Hancock, J., Hay, R. J., Hunter-Merrill, R., Huynh, C., Hosgood, H. D., Johnson, C. O., Jonas, J. B., Khubchandani, J., Kumar, G. A., Kutz, M., Lan, Q., Larson, H. J., Liang, X., Lim, S. S., Lopez, A. D., MacIntyre, M. F., Marczak, L., Marquez, N., Mokdad, A. H., Pinho, C., Pourmalek, F., Salomon, J. A., Sanabria, J. R., Sandar, L., Sartorius, B., Schwartz, S. M., Shackelford, K. A., Shibuya, K., Stanaway, J., Steiner, C., Sun, J., Takahashi, K., Vollset, S. E., Vos, T., Wagner, J. A., Wang, H., Westerman, R., Zeeb, H., Zoeckler, L., Abd-Allah, F., Ahmed, M. B., Alabed, S., Alam, N. K., Aldhahri, S. F., Alem, G., Alemayohu, M. A., Ali, R., Al-Raddadi, R., Amare, A., Amoako, Y., Artaman, A., Asayesh, H., Atnafu, N., Awasthi, A., Saleem, H. B., Barac, A., Bedi, N., Bensenor. I., Berhane, A., Bernabe, E., Betsu, B., Binagwaho, A., Boneya, D., Campos-Nonato, I., Castaneda-Orjula, C., Catala-Lopez, F., Chiang, P., Chibueze, C., Chitheer, A., Choi, J. Y., Cowie, B., Damtew, S., das Neves, J., Dey, S., Dharmaratne, S., Dhillon, P., Ding, E., Driscoll, T., Ekwueme, D., Endries, A. Y., Farvid, M., Farzadfar, F., Fernandes, J., Fischer, F., G/Hiwot, T. T., Gebru, A., Gopalani, S., Hailu, A., Horino, M., Horita, N., Husseini, A., Huybrechts, I., Inoue, M., Islami, F., Jakovljevic, M., James, S., Javanbakht, M., Jee, S. H., Kasaeian, A., Kedir, M. S., Khader, Y. S., Khang, Y. H., Kim, D., Leigh, J., Linn, S., Lunevicius, R., El Razek, H. M. A., Malekzadeh, R., Malta, D. C., Marcenes, W., Markos, D., Melaku, Y. A., Meles, K. G., Mendoza, W., Mengiste, D. T., Meretoja, T. J., Miller, T. R., Mohammad, K. A., Mohammadi, A., Mohammed, S., Moradi-Lakeh, M., Nagel, G., Nand, D., Le Nguyen, Q., Nolte, S., Ogbo, F. A., Oladimeji, K. E., Oren, E., Pa, M., Park, E. K., Pereira, D. M., Plass, D., Qorbani, M., Radfar, A., Rafay, A., Rahman, M., Rana, S. M., Soreide, K., Satpathy, M., Sawhney, M., Sepanlou, S. G., Shaikh, M. A., She, J., Shiue, I., Shore, H. R., Shrime, M. G., So, S., Soneji, S., Stathopoulou, V., Stroumpoulis, K., Sufiyan, M. B., Sykes, B. L., Tabares-Seisdedos, R., Tadese, F., Tedla, B. A., Tessema, G. A., Thakur, J. S., Tran, B. X., Ukwaja, K. N., Uzochukwu, B. S. C., Vlassov, V. V., Weiderpass, E., Wubshet Terefe, M., Yebyo, H. G., Yimam, H. H., Yonemoto, N., Younis, M. Z., Yu, C., Zaidi, Z., Zaki, M. E. S., Zenebe, Z. M., Murray, C. J. L. and Naghavi, M. (2017) Global, regional, and national cancer incidence, mortality, years of life lost, years lived with disability, and disability-adjusted life-years for 32 cancer groups, 1990 to 2015: a systematic analysis for the global burden of disease study. JAMA Oncol. 3, 524-548. https://doi.org/10.1001/jamaoncol.2016.5688
  26. Frisancho, A. R. (1974) Triceps skin fold and upper arm muscle size norms for assessment of nutrition status. Am. J. Clin. Nutr. 27, 1052-1058.
  27. Gewirtz, D. A. (1999) A critical evaluation of the mechanisms of action proposed for the antitumor effects of the anthracycline antibiotics adriamycin and daunorubicin. Biochem. Pharmacol. 57, 727-741. https://doi.org/10.1016/S0006-2952(98)00307-4
  28. Grodstein, F., Newcomb, P. A. and Stampfer, M. J. (1999) Postmenopausal hormone therapy and the risk of colorectal cancer: a review and meta-analysis. Am. J. Med. 106, 574-582. https://doi.org/10.1016/S0002-9343(99)00063-7
  29. Harris, B. E., Carpenter, J. T. and Diasio, R. B. (1991) Severe 5-fluorouracil toxicity secondary to dihydropyrimidine dehydrogenase deficiency. A potentially more common pharmacogenetic syndrome. Cancer 68, 499-501. https://doi.org/10.1002/1097-0142(19910801)68:3<499::AID-CNCR2820680309>3.0.CO;2-F
  30. Hayes, J. D. and Strange, R. C. (2000) Glutathione S-transferase polymorphisms and their biological consequences. Pharmacology 61, 154-166. https://doi.org/10.1159/000028396
  31. Hsu, Y. T., Wolter, K. G. and Youle, R. J. (1997) Cytosol-to-membrane redistribution of Bax and Bcl-X(L) during apoptosis. Proc. Natl. Acad. Sci. U.S.A. 94, 3668-3672. https://doi.org/10.1073/pnas.94.8.3668
  32. Huang, R. S., Kistner, E. O., Bleibel, W. K., Shukla, S. J. and Dolan, M. E. (2007) Effect of population and gender on chemotherapeutic agent-induced cytotoxicity. Mol. Cancer Ther. 6, 31-36.
  33. Islam, M. M., Iqbal, U., Walther, B. A., Nguyen, P. A., Li, Y. J., Dubey, N. K., Poly, T. N., Masud, J. H. B., Atique, S. and Syed-Abdul, S. (2017) Gender-based personalized pharmacotherapy: a systematic review. Arch. Gynecol. Obstet. 295, 1305-1317. https://doi.org/10.1007/s00404-017-4363-3
  34. Joerger, M., Huitema, A. D., van den Bongard, D. H., Schellens, J. H. and Beijnen, J. H. (2006) Quantitative effect of gender, age, liver function, and body size on the population pharmacokinetics of Paclitaxel in patients with solid tumors. Clin. Cancer. Res. 12, 2150-2157. https://doi.org/10.1158/1078-0432.CCR-05-2069
  35. Jordan, M. A. and Wilson. (2004) Microtubules as a target for anticancer drugs. Nat. Rev. Cancer 4, 253-265. https://doi.org/10.1038/nrc1317
  36. Keitt, S. K., Fagan, T. F. and Marts, S. A. (2004) Understanding sex differences in environmental health: a thought leaders' roundtable. Environ. Health Perspect. 112, 604-609.
  37. Kim, S. E., Paik, H. Y., Yoon, H., Lee, J. E., Kim, N. and Sung, M. K. (2015) Sex- and gender-specific disparities in colorectal cancer risk. World J. Gastroenterol. 21, 5167-5175. https://doi.org/10.3748/wjg.v21.i17.5167
  38. Lee, M. L., Chen, G. G., Vlantis, A. C., Tse, G. M., Leung, B. C. and van Hasselt, C. A. (2005) Induction of thyroid papillary carcinoma cell proliferation by estrogen is associated with an altered expression of Bcl-xL. Cancer J. 11, 113-121. https://doi.org/10.1097/00130404-200503000-00006
  39. Ley, C. J., Lees, B. and Stevenson, J. C. (1992) Sex- and menopause-associated changes in body-fat distribution. Am. J. Clin. Nutr. 55, 950-954. https://doi.org/10.1093/ajcn/55.5.950
  40. Liaw, C. C., Wang, C. H., Chang, H. K., Liau, C. T., Yeh, K. Y., Huang, J. S. and Lin, Y. C. (2001) Gender discrepancy observed between chemotherapy-induced emesis and hiccups. Support Care Cancer 9, 435-441. https://doi.org/10.1007/s005200000231
  41. Lipshultz, S. E., Colan, S. D., Gelber, R. D., Perez-Atayde, A. R., Sallan, S. E. and Sanders, S. P. (1991) Late cardiac effects of doxorubicin therapy for acute lymphoblastic leukemia in childhood. N. Engl. J. Med. 324, 808-815. https://doi.org/10.1056/NEJM199103213241205
  42. Lipshultz, S. E., Lipsitz, S. R., Mone, S. M., Goorin, A. M., Sallan, S. E., Sanders, S. P., Orav, E. J., Gelber, R. D. and Colan, S. D. (1995) Female sex and higher drug dose as risk factors for late cardiotoxic effects of doxorubicin therapy for childhood cancer. N. Engl. J. Med. 332, 1738-1743. https://doi.org/10.1056/NEJM199506293322602
  43. Longley, D. B., Harkin, D. P. and Johnston, P. G. (2003) 5-fluorouracil: mechanisms of action and clinical strategies. Nat. Rev. Cancer 3, 330-338. https://doi.org/10.1038/nrc1074
  44. Lu, J. F., Bruno, R., Eppler, S., Novotny, W., Lum, B. and Gaudreault, J. (2008) Clinical pharmacokinetics of bevacizumab in patients with solid tumors. Cancer Chemother. Pharmacol. 62, 779-786. https://doi.org/10.1007/s00280-007-0664-8
  45. Mader, R. M. (2007) The potential of gender-specific tumor pharmacology. Pharmacogenomics 8, 271-274. https://doi.org/10.2217/14622416.8.3.271
  46. Mannervik, B. and Danielson, U. H. (1988) Glutathione transferases--structure and catalytic activity. CRC Crit. Rev. Biochem. 23, 283-337. https://doi.org/10.3109/10409238809088226
  47. McMichael, A. J. and Potter, J. D. (1980) Reproduction, endogenous and exogenous sex hormones, and colon cancer: a review and hypothesis. J. Natl. Cancer. Inst. 65, 1201-1207.
  48. Merkatz, R. B., Temple, R., Subel, S., Feiden, K. and Kessler, D. A. (1993) Women in clinical trials of new drugs. A change in Food and Drug Administration policy. The working group on women in clinical trials. N. Engl. J. Med. 329, 292-296. https://doi.org/10.1056/NEJM199307223290429
  49. Milano, G., Etienne, M. C., Cassuto-Viguier, E., Thyss, A., Santini, J., Frenay, M., Renee, N., Schneider, M. and Demard, F. (1992) Influence of sex and age on fluorouracil clearance. J. Clin. Oncol. 10, 1171-1175. https://doi.org/10.1200/JCO.1992.10.7.1171
  50. Milano, G., Etienne, M. C., Pierrefite, V., Barberi-Heyob, M., Deporte-Fety, R. and Renee, N. (1999) Dihydropyrimidine dehydrogenase deficiency and fluorouracil-related toxicity. Br. J. Cancer 79, 627-630. https://doi.org/10.1038/sj.bjc.6690098
  51. Mitry, M. A. and Edwards, J. G. (2016) Doxorubicin induced heart failure: phenotype and molecular mechanisms. Int. J. Cardiol. Heart Vasc. 10,17-24.
  52. Muller, C., Murawski, N., Wiesen, M. H., Held, G., Poeschel, V., Zeynalova, S., Wenger, M., Nickenig, C., Peter, N., Lengfelder, E., Metzner, B., Rixecker, T., Zwick, C., Pfreundschuh, M. and Reiser, M. (2012) The role of sex and weight on rituximab clearance and serum elimination half-life in elderly patients with DLBCL. Blood 119, 3276-3284. https://doi.org/10.1182/blood-2011-09-380949
  53. Naghavi, M., Abajobir, A. A., Abbafati, C., Abbas, K. M., Abd-Allah, F., Abera, S. F., Aboyans, V., Adetokunboh, O., Afshin, A., Agrawal, A., Ahmadi, A., Ahmed, M. B., Aichour, A. N., Aichour, M. T. E., Aichour, I., Aiyar, S., Alahdab, F., Al-Aly, Z., Alam, K., Alam, N., Alam, T., Alene, K. A., Al-Eyadhy, A., Ali, S. D., Alizadeh-Navaei, R., Alkaabi, J. M., Alkerwi, A., Alla, F., Allebeck, P., Allen, C., Al-Raddadi, R., Alsharif, U., Altirkawi, K. A., Alvis-Guzman, N., Amare, A. T., Amini, E., Ammar, W., Amoako, Y. A., Anber, N., Andersen, H. H., Andrei, C. L., Androudi, S., Ansari, H., Antonio, C. A. T., Anwari, P., Arnlov, J., Arora, M., Artaman, A., Aryal, K. K., Asayesh, H., Asgedom, S. W., Atey, T. M., Avila-Burgos, L., Avokpaho, E. F. G., Awasthi, A., Babalola, T. K., Bacha, U., Balakrishnan, K., Barac, A., Barboza, M. A., Barker-Collo, S. L., Barquera, S., Barregard, L., Barrero, L. H., Baune, B. T., Bedi, N., Beghi, E., Bejot, Y., Bekele, B. B., Bell, M. L., Bennett, J. R., Bensenor, I. M., Berhane, A., Bernabe, E., Betsu, B. D., Beuran, M., Bhatt, S., Biadgilign, S., Bienhoff, K., Bikbov, B., Bisanzio, D., Bourne, R. R. A., Breitborde, N. J. K., Bulto, L. N. B., Bumgarner, B. R., Butt, Z. A., Cahuana-Hurtado, L., Cameron, E., Campuzano, J. C., Car, J., Cardenas, R., Carrero, J. J., Carter, A., Casey, D. C., Castaneda-Orjuela, C. A., Catala-Lopez, F., Charlson, F. J., Chibueze, C. E., Chimed-Ochir, O., Chisumpa, V. H., Chitheer, A. A., Christopher, D. J., Ciobanu, L. G., Cirillo, M., Cohen, A. J., Colombara, D., Cooper, C., Cowie, B. C., Criqui, M. H., Dandona, L., Dandona, R., Dargan, P. I., das Neves, J., Davitoiu, D. V., Davletov, K., de Courten, B., Defo, B. K., Degenhardt, L., Deiparine, S., Deribe, K., Deribew, A., Dey, S., Dicker, D., Ding, E. L., Djalalinia, S., Do, H. P., Doku, D. T., Douwes-Schultz, D., Driscoll, T. R., Dubey, M., Duncan, B. B., Echko, M., El-Khatib, Z. Z., Ellingsen, C. L., Enayati, A., Ermakov, S. P., Erskine, H. E., Eskandarieh, S., Esteghamati, A., Estep, K., Farinha, C. S. E. S., Faro, A., Farzadfar, F., Feigin, V. L., Fereshtehnejad, S. M., Fernandes, J. C., Ferrari, A. J., Feyissa, T. R., Filip, I., Finegold, S., Fischer, F., Fitzmaurice, C., Flaxman, A. D., Foigt, N., Frank, T., Fraser, M., Fullman, N., Furst, T., Furtado, J. M., Gakidou, E., Garcia-Basteiro, A. L., Gebre, T., Gebregergs, G. B., Gebrehiwot, T. T., Gebremichael, D. Y., Geleijnse, J. M., Genova-Maleras, R., Gesesew, H. A., Gething, P. W., Gillum, R. F., Giref, A. Z., Giroud, M., Giussani, G., Godwin, W. W., Gold, A. L, Goldberg, E. M., Gona, P. N., Gopalani, S. V., Gouda, H. N., Goulart, A. C., Griswold, M., Gupta, R., Gupta, T., Gupta, V., Gupta, P. C., Haagsma, J. A., Hafezi-Nejad, N., Hailu, A. D., Hailu, G. B., Hamadeh, R. R., Hambisa, M. T., Hamidi, S., Hammami, M., Hancock, J., Handal, A. J., Hankey, G. J., Hao, Y., Harb, H. L., Hareri, H. A., Hassanvand, M. S., Havmoeller, R., Hay, S. I., He, F., Hedayati, M. T., Henry, N. J., Heredia-Pi, I. B., Herteliu, C., Hoek, H. W., Horino, M., Horita, N., Hosgood, H. D., Hostiuc, S., Hotez, P. J., Hoy, D. G., Huynh, C., Iburg, K. M., Ikeda, C., Ileanu, B. V., Irenso, A. A., Irvine, C. M. S., Islam, S. M. S., Jacobsen, K. H., Jahanmehr, N., Jakovljevic, M. B., Javanbakht, M., Jayaraman, S. P., Jeemon, P., Jha, V., John, D., Johnson, C. O., Johnson, S. C., Jonas, J. B., Jurisson, M., Kabir, Z., Kadel, R., Kahsay, A., Kamal, R., Karch, A., Karimi, S. M., Karimkhani, C., Kasaeian, A., Kassaw, N. A., Kassebaum, N. J., Katikireddi, S. V., Kawakami, N., Keiyoro, P. N., Kemmer, L., Kesavachandran, C. N., Khader, Y. S., Khan, E. A., Khang, Y. H., Khoja, A. T. A., Khosravi, M. H., Khosravi, A., Khubchandani, J., Kiadaliri, A. A., Kieling, C., Kievlan, D., Kim, Y. J., Kim, D., Kimokoti, R. W., Kinfu, Y., Kissoon, N., Kivimaki, M., Knudsen, A. K., Kopec, J. A., Kosen, S., Koul, P. A., Koyanagi, A., Kulikoff, X. R., Kumar, G. A., Kumar, P., Kutz, M., Kyu, H. H., Lal, D. K., Lalloo, R., Lambert, T. L. N., Lan, Q., Lansingh, V. C., Larsson, A., Lee, P. H., Leigh, J., Leung, J., Levi, M., Li, Y., Li Kappe, D., Liang, X., Liben, M. L., Lim, S. S., Liu, P. Y., Liu, A., Liu, Y., Lodha, R., Logroscino, G., Lorkowski, S., Lotufo, P. A., Lozano, R., Lucas, T. C. D., Ma, S., Macarayan, E. R. K., Maddison, E. R., Magdy Abd El Razek, M., Majdan, M., Majdzadeh, R., Majeed, A., Malekzadeh, R., Malhotra, R., Malta, D. C., Manguerra, H., Manyazewal, T., Mapoma, C. C., Marczak, L. B., Markos, D., Martinez-Raga, J., Martins-Melo, F. R., Martopullo, I., McAlinden, C., McGaughey, M., McGrath, J. J., Mehata, S., Meier, T., Meles, K. G., Memiah, P., Memish, Z. A., Mengesha, M. M., Mengistu, D. T., Menota, B. G., Mensah, G. A., Meretoja, T. J., Meretoja, A., Millear, A., Miller, T. R., Minnig, S., Mirarefin, M., Mirrakhimov, E. M., Misganaw, A., Mishra, S. R., Mohamed, I. A., Mohammad, K. A., Mohammadi, A., Mohammed, S., Mokdad, A. H., Mola, G. L. D., Mollenkopf, S. K., Molokhia, M., Monasta, L., Montanez, J. C., Montico, M., Mooney, M. D., Moradi-Lakeh, M., Moraga, P., Morawska, L., Morozoff, C., Morrison, S. D., Mountjoy-Venning, C., Mruts, K. B., Muller, K., Murthy, G. V. S., Musa, K. I., Nachega, J. B., Naheed, A., Naldi, L., Nangia, V., Nascimento, B. R., Nasher, J. T., Natarajan, G., Negoi, I., Ngunjiri, J. W., Nguyen, C. T., Nguyen, Q. L., Nguyen, T. H., Nguyen, G., Nguyen, M., Nichols, E., Ningrum, D. N. A., Nong, V. M., Noubiap, J. J. N., Ogbo, F. A., Oh, I. H., Okoro, A., Olagunju, A. T., Olsen, H. E., Olusanya, B. O., Olusanya, J. O., Ong, K., Opio, J. N., Oren, E., Ortiz, A., Osman, M., Ota, E., Pa, M., Pacella, R. E., Pakhale, S., Pana, A., Panda, B. K., Panda-Jonas, S., Papachristou, C., Park, E. K., Patten, S. B., Patton, G. C., Paudel, D., Paulson, K., Pereira, D. M., Perez-Ruiz, F., Perico, N., Pervaiz, A., Petzold, M., Phillips, M. R., Pigott, D. M., Pinho, C., Plass, D., Pletcher, M. A., Polinder, S., Postma, M. J., Pourmalek, F., Purcell, C., Qorbani, M., Quintanilla, B. P. A., Radfar, A., Rafay, A., Rahimi-Movaghar, V., Rahman, M. H. U., Rahman, M., Rai, R. K., Ranabhat, C. L., Rankin, Z., Rao, P. C., Rath, G. K., Rawaf, S., Ray, S. E., Rehm, J., Reiner, R. C., Reitsma, M. B., Remuzzi, G., Rezaei, S., Rezai, M. S., Rokni, M. B., Ronfani, L., Roshandel, G., Roth, G. A., Rothenbacher, D., Ruhago, G. M., Sa, R., Saadat, S., Sachdev, P. S., Sadat, N., Safdarian, M., Safi, S., Safiri, S., Sagar, R., Sahathevan, R., Salama, J., Salamati, P., Salomon, J. A., Samy, A. M., Sanabria, J. R., Sanchez-Nino, M. D., Santomauro, D., Santos, I. S., Santric Milicevic, M. M., Sartorius, B., Satpathy, M., Schmidt, M. I., Schneider, I. J. C., Schulhofer-Wohl, S., Schutte, A. E., Schwebel, D. C., Schwendicke, F., Sepanlou, S. G., Servan-Mori, E. E., Shackelford, K. A., Shahraz, S., Shaikh, M. A., Shamsipour, M., Shamsizadeh, M., Sharma, J., Sharma, R., She, J., Sheikhbahaei, S., Shey, M., Shi, P., Shields, C., Shigematsu, M., Shiri, R., Shirude, S., Shiue, I., Shoman, H., Shrime, M. G., Sigfusdottir, I. D., Silpakit, N., Silva, J. P., Singh, J. A., Singh, A., Skiadaresi, E., Sligar, A., Smith, D. L., Smith, A., Smith, M., Sobaih, B. H. A., Soneji, S., Sorensen, R. J. D., Soriano, J. B., Sreeramareddy, C. T., Srinivasan, V., Stanaway, J. D., Stathopoulou, V., Steel, N., Stein, D. J., Steiner, C., Steinke, S., Stokes, M. A., Strong, M., Strub, B., Subart, M., Sufiyan, M. B., Sunguya, B. F., Sur, P. J., Swaminathan, S., Sykes, B. L., Tabares-Seisdedos, R., Tadakamadla, S. K., Takahashi, K., Takala, J. S., Talongwa, R. T., Tarawneh, M. R., Tavakkoli, M., Taveira, N., Tegegne, T. K., Tehrani-Banihashemi, A., Temsah, M. H., Terkawi, A. S., Thakur, J. S., Thamsuwan, O., Thankappan, K. R., Thomas, K. E., Thompson, A. H., Thomson, A. J., Thrift, A. G., Tobe-Gai, R., Topor-Madry, R., Torre, A., Tortajada, M., Towbin, J. A., Tran, B. X., Troeger, C., Truelsen, T., Tsoi, D., Tuzcu, E. M., Tyrovolas, S., Ukwaja, K. N., Undurraga, E. A., Updike, R., Uthman, O. A., Uzochukwu, B. S. C., van Boven, J. F. M., Vasankari, T., Venketasubramanian, N., Violante, F. S., Vlassov, V. V., Vollset, S. E., Vos, T., Wakayo, T., Wallin, M. T., Wang, Y. P., Weiderpass, E., Weintraub, R. G., Weiss, D. J., Werdecker, A., Westerman, R., Whetter, B., Whiteford, H. A., Wijeratne, T., Wiysonge, C. S., Woldeyes, B. G., Wolfe, C. D. A., Woodbrook, R., Workicho, A., Xavier, D., Xiao, Q., Xu, G., Yaghoubi, M., Yakob, B., Yano, Y., Yaseri, M., Yimam, H. H., Yonemoto, N., Yoon, S. J., Yotebieng, M., Younis, M. Z., Zaidi, Z., Zaki, M. E. S., Zegeye, E. A., Zenebe, Z. M., Zerfu, T. A., Zhang, A. L., Zhang, X., Zipkin, B., Zodpey, S., Lopez, A. D. and Murray, C. J. L. (2017) Global, regional, and national age-sex specific mortality for 264 causes of death, 1980-2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet 390, 1151-1210. https://doi.org/10.1016/S0140-6736(17)32152-9
  54. Rademaker, M. (2001) Do women have more adverse drug reactions? Am. J. Clin. Dermatol. 2, 349-351. https://doi.org/10.2165/00128071-200102060-00001
  55. Raftogianis, R. B., Wood, T. C., Otterness, D. M., Van Loon, J. A. and Weinshilboum, R. M. (1997) Phenol sulfotransferase pharmacogenetics in humans: association of common SULT1A1 alleles with TS PST phenotype. Biochem. Biophys. Res. Commun. 239, 298-304. https://doi.org/10.1006/bbrc.1997.7466
  56. Riihijarvi, S., Taskinen, M., Jerkeman, M. and Leppa, S. (2011) Male gender is an adverse prognostic factor in B-cell lymphoma patients treated with immunochemotherapy. Eur. J. Haematol. 86, 124-128. https://doi.org/10.1111/j.1600-0609.2010.01541.x
  57. Rivankar, S. (2014) An overview of doxorubicin formulations in cancer therapy. J. Cancer Res. Ther. 10, 853-858. https://doi.org/10.4103/0973-1482.139267
  58. Rodvold, K. A., Rushing, D. A. and Tewksbury, D. A. (1988) Doxorubicin clearance in the obese. J. Clin. Oncol. 6, 1321-1327. https://doi.org/10.1200/JCO.1988.6.8.1321
  59. Sandler, A., Gray, R., Perry, M. C., Brahmer, J., Schiller, J. H., Dowlati, A., Lilenbaum, R. and Johnson, D. H. (2006) Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer. N. Engl. J. Med. 355, 2542-2550. https://doi.org/10.1056/NEJMoa061884
  60. Santi, D. V., McHenry, C. S. and Sommer, H. (1974) Mechanism of interaction of thymidylate synthetase with 5-fluorodeoxyuridylate. Biochemistry 13, 471-481. https://doi.org/10.1021/bi00700a012
  61. Schiff, P. B. and Horwitz, S. B. (1980) Taxol stabilizes microtubules in mouse fibroblast cells. Proc. Natl. Acad. Sci. U.S.A. 77, 1561-1565. https://doi.org/10.1073/pnas.77.3.1561
  62. Schmetzer, O. and Florcken, A. (2012) Sex differences in the drug therapy for oncologic diseases. In Sex and Gender Differences in Pharmacology (V. Regitz-Zagrosek, Ed.), pp. 411-442. Springer, Germany.
  63. Schuetz, E. G., Furuya, K. N. and Schuetz, J. D. (1995) Interindividual variation in expression of P-glycoprotein in normal human liver and secondary hepatic neoplasms. J. Pharmacol. Exp. Ther. 275, 1011-1018.
  64. Siegel, R. L., Miller, K. D. and Jemal, A. (2016) Cancer statistics, 2016. CA Cancer J. Clin. 66, 7-30 https://doi.org/10.3322/caac.21332
  65. Siegel, R. L., Miller, K. D. and Jemal, A. (2017) Cancer statistics, 2017. CA Cancer J. Clin. 67, 7-30. https://doi.org/10.3322/caac.21387
  66. Sloan, J. A., Goldberg, R. M., Sargent, D. J., Vargas-Chanes, D., Nair, S., Cha, S. S., Novotny, P. J., Poon, M. A., O'Connell, M. J. and Loprinzi, C. L. (2002) Women experience greater toxicity with fluorouracil-based chemotherapy for colorectal cancer. J. Clin. Oncol. 20, 1491-1498. https://doi.org/10.1200/JCO.2002.20.6.1491
  67. Stein, B. N., Petrelli, N. J., Douglass, H. O., Driscoll, D. L., Arcangeli, G. and Meropol, N. J. (1995) Age and sex are independent predictors of 5-fluorouracil toxicity. Analysis of a large scale phase III trial. Cancer 75, 11-17. https://doi.org/10.1002/1097-0142(19950101)75:1<11::AID-CNCR2820750104>3.0.CO;2-N
  68. Torre, L. A., Siegel, R. L., Ward, E. M. and Jemal, A. (2016) Global cancer incidence and mortality rates and trends--an update. Cancer Epidemiol. Biomarkers Prev. 25, 16-27. https://doi.org/10.1158/1055-9965.EPI-15-0578
  69. Tran, C., Knowles, S. R., Liu, B. A. and Shear, N. H. (1998) Gender differences in adverse drug reactions. J. Clin. Pharmacol. 38, 1003-1009.
  70. Traver, R. D., Horikoshi, T., Danenberg, K. D., Stadlbauer, T. H., Danenberg, P. V., Ross, D. and Gibson, N. W. (1992) NAD(P)H:quinone oxidoreductase gene expression in human colon carcinoma cells: characterization of a mutation which modulates DT-diaphorase activity and mitomycin sensitivity. Cancer Res. 52, 797-802.
  71. van Asperen, J., van Tellingen, O., Tijssen, F., Schinkel, A. H. and Beijnen, J. H. (1999) Increased accumulation of doxorubicin and doxorubicinol in cardiac tissue of mice lacking mdr1a P-glycoprotein. Br. J. Cancer 79, 108-113. https://doi.org/10.1038/sj.bjc.6690019
  72. Wang, J. and Huang, Y. (2007) Pharmacogenomics of sex difference in chemotherapeutic toxicity. Curr. Drug Discov. Technol. 4, 59-68. https://doi.org/10.2174/157016307781115485
  73. Wasternack, C. (1980) Degradation of pyrimidines and pyrimidine analogs--pathways and mutual influences. Pharmacol. Ther. 8, 629-651. https://doi.org/10.1016/0163-7258(80)90079-0
  74. Wei, Q., Cheng, L., Amos, C. I., Wang, L. E., Guo, Z., Hong, W. K. and Spitz, M. R. (2000) Repair of tobacco carcinogen-induced DNA adducts and lung cancer risk: a molecular epidemiologic study. J. Natl. Cancer Inst. 92, 1764-1772. https://doi.org/10.1093/jnci/92.21.1764
  75. Wongtawatchai, T., Agthong, S., Kaewsema, A. and Chentanez, V. (2009) Sex-related differences in cisplatin-induced neuropathy in rats. J. Med. Assoc. Thai. 92, 1485-1491.
  76. Yamamoto, H., Sekine, I., Yamada, K., Nokihara, H., Yamamoto, N., Kunitoh, H., Ohe, Y. and Tamura, T. (2008) Gender differences in treatment outcomes among patients with non-small cell lung cancer given a combination of carboplatin and paclitaxel. Oncology 75, 169-174. https://doi.org/10.1159/000159268
  77. Yoshioka, A., Tanaka, S., Hiraoka, O., Koyama, Y., Hirota, Y., Ayusawa, D., Seno, T., Garrett, C. and Wataya, Y. (1987) Deoxyribonucleoside triphosphate imbalance. 5-Fluorodeoxyuridine-induced DNA double strand breaks in mouse FM3A cells and the mechanism of cell death. J. Biol. Chem. 262, 8235-8241.
  78. Zheng, L., Wang, Y., Schabath, M. B., Grossman, H. B. and Wu, X. (2003) Sulfotransferase 1A1 (SULT1A1) polymorphism and bladder cancer risk: a case-control study. Cancer Lett. 202, 61-69. https://doi.org/10.1016/j.canlet.2003.08.007
  79. Zucker, I. and Beery, A. K. (2010) Males still dominate animal studies. Nature 465, 690. https://doi.org/10.1038/465690a

Cited by

  1. Understanding sex differences in the regulation of cancer-induced muscle wasting pp.1751-4258, 2018, https://doi.org/10.1097/SPC.0000000000000380
  2. Incidence of chronic myeloid leukemia in Calgary, Alberta, Canada vol.11, pp.1, 2018, https://doi.org/10.1186/s13104-018-3890-8
  3. Sexual dimorphism in solid and hematological malignancies pp.1863-2300, 2018, https://doi.org/10.1007/s00281-018-0724-7