Sex differences in cancer: Epidemiology, genetics and therapy

Biomolecules and Therapeutics

Volumn 26, Issue 4, 2018, Pages 335-342

  Kim, Hae In ^a   Lim, Hyesol ^a   Moon, Aree ^a  

^a Duksung Women's University   (South Korea)

Author keywords

Cancer; Chemotherapy; Sex difference; Sex hormone

Indexed keywords

BEVACIZUMAB; CARBOPLATIN; CISPLATIN; DOXORUBICIN; FLUOROURACIL; PACLITAXEL; RITUXIMAB; SEX HORMONE;

ABDOMINAL PAIN; ALOPECIA; ANTINEOPLASTIC ACTIVITY; AUTOIMMUNE DISEASE; BREAST CANCER; CANCER CHEMOTHERAPY; CANCER GENETICS; CANCER INCIDENCE; CANCER MORTALITY; CANCER SUSCEPTIBILITY; CANCER THERAPY; CHILDHOOD LEUKEMIA; CHRONIC LYMPHATIC LEUKEMIA; COLORECTAL CANCER; DIARRHEA; DIFFUSE LARGE B CELL LYMPHOMA; DRUG BLOOD LEVEL; DRUG CLEARANCE; DRUG EFFICACY; DRUG ELIMINATION; DRUG METABOLISM; DRUG SAFETY; FOLLICULAR LYMPHOMA; HEMATOLOGIC MALIGNANCY; HUMAN; HYPERTENSION; LEUKOPENIA; LUNG CANCER; LUNG CARCINOMA; LYMPHOMA; MALIGNANT NEOPLASM; NAUSEA; NEUTROPENIA; NON SMALL CELL LUNG CANCER; NONHODGKIN LYMPHOMA; NONHUMAN; PERSONALIZED MEDICINE; PROGRESSION FREE SURVIVAL; REVIEW; SEX DIFFERENCE; SINGLE NUCLEOTIDE POLYMORPHISM; STOMACH CANCER; STOMATITIS; THYROID CANCER; VOMITING;

EID: 85049779838     PISSN: 19769148     EISSN: 20054483     Source Type: Journal    
DOI: 10.4062/biomolther.2018.103     Document Type: Review

References (79)

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.
2. Arand, M., Mühlbauer, R., Hengstler, J., Jäger, 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.
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.
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.
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.
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.
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.
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.
10. Bolufer, P., Collado, M., Barragán, E., Cervera, J., Calasanz, M. J., Colomer, D., Roman-Gómez, 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.
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 East- ern 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.
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.
15. Diasio, R. B. and Harris, B. E. (1989) Clinical pharmacology of 5-fluorouracil. Clin. Pharmacokinet. 16, 215-237.
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.
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.
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.
20. Etienne, M. C., Lagrange, J. L., Dassonville, O., Fleming, R., Thyss, A., Renée, N., Schneider, M., Demard, F. and Milano, G. (1994) Population study of dihydropyrimidine dehydrogenase in cancer patients. J. Clin. Oncol. 12, 2248-2253.
21. Everson, G. T., McKinley, C. and Kern, F., Jr. (1991) Mechanisms of gallstone formation in women. Effects of exogenous estrogen (Pre-marin) and dietary cholesterol on hepatic lipid metabolism. J. Clin. Invest. 87, 237-246.
22. Fagerholm, R., Hofstetter, B., Tommiska, J., Aaltonen, K., Vrtel, R., Syrjäkoski, K., Kallioniemi, A., Kilpivaara, O., Mannermaa, A., Kos-ma, V. M., Uusitupa, M., Eskelinen, M., Kataja, V., Aittomäki, K., von Smitten, K., Heikkilä, 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.
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.
24. Ferrara, N. (2004) Vascular endothelial growth factor: basic science and clinical progress. Endocr. Rev. 25, 581-611.
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., Alemayo-hu, 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., Bernabé, E., Betsu, B., Binag-waho, A., Boneya, D., Campos-Nonato, I., Castañeda-Orjula, C., Catalá-López, 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., Søreide, 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., Tabarés-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.
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.
28. Grodstein, F., Newcomb, P. A. and Stampfer, M. J. (1999) Postmeno-pausal hormone therapy and the risk of colorectal cancer: a review and meta-analysis. Am. J. Med. 106, 574-582.
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.
30. Hayes, J. D. and Strange, R. C. (2000) Glutathione S-transferase polymorphisms and their biological consequences. Pharmacology 61, 154-166.
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.
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.
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.
35. Jordan, M. A. and Wilson. (2004) Microtubules as a target for antican-cer drugs. Nat. Rev. Cancer 4, 253-265.
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.
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.
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.
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.
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.
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 cardio-toxic effects of doxorubicin therapy for childhood cancer. N. Engl. J. Med. 332, 1738-1743.
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.
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.
45. Mader, R. M. (2007) The potential of gender-specific tumor pharmacology. Pharmacogenomics 8, 271-274.
46. Mannervik, B. and Danielson, U. H. (1988) Glutathione transferases--structure and catalytic activity. CRC Crit. Rev. Biochem. 23, 283-337.
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.
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.
50. Milano, G., Etienne, M. C., Pierrefite, V., Barberi-Heyob, M., Deporte-Fety, R. and Renée, N. (1999) Dihydropyrimidine dehydrogenase deficiency and fluorouracil-related toxicity. Br. J. Cancer 79, 627-630.
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. Müller, C., Murawski, N., Wiesen, M. H., Held, G., Poeschel, V., Zey-nalova, 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.
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., Ärnlöv, 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., Béjot, Y., Bekele, B. B., Bell, M. L., Bennett, J. R., Bensenor, I. M., Berhane, A., Bernabé, 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., Cárdenas, R., Carrero, J. J., Carter, A., Casey, D. C., Castañeda-Orjuela, C. A., Catalá-López, F., Charl-son, 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., Es-kandarieh, 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., Fürst, T., Furtado, J. M., Gakidou, E., Gar-cia-Basteiro, A. L., Gebre, T., Gebregergs, G. B., Gebrehiwot, T. T., Gebremichael, D. Y., Geleijnse, J. M., Genova-Maleras, R., Gese-sew, 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., Ham-bisa, 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., Jürisson, 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., Kes-avachandran, 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., Lorkows-ki, 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., Mir-rakhimov, 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., Mon-tañez, J. C., Montico, M., Mooney, M. D., Moradi-Lakeh, M., Mora-ga, P., Morawska, L., Morozoff, C., Morrison, S. D., Mountjoy-Ven-ning, 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., Pat-ten, 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., Reits-ma, M. B., Remuzzi, G., Rezaei, S., Rezai, M. S., Rokni, M. B., Ronfani, L., Roshandel, G., Roth, G. A., Rothenbacher, D., Ruha-go, G. M., Sa, R., Saadat, S., Sachdev, P. S., Sadat, N., Safdarian, M., Safi, S., Safiri, S., Sagar, R., Sahathevan, R., Salama, J., Sala-mati, P., Salomon, J. A., Samy, A. M., Sanabria, J. R., Sanchez-Niño, 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., Schwen-dicke, 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., Tabarés-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., Venketasubra-manian, 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.
54. Rademaker, M. (2001) Do women have more adverse drug reactions? Am. J. Clin. Dermatol. 2, 349-351.
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.
56. Riihijärvi, S., Taskinen, M., Jerkeman, M. and Leppä, S. (2011) Male gender is an adverse prognostic factor in B-cell lymphoma patients treated with immunochemotherapy. Eur. J. Haematol. 86, 124-128.
57. Rivankar, S. (2014) An overview of doxorubicin formulations in cancer therapy. J. Cancer Res. Ther. 10, 853-858.
58. Rodvold, K. A., Rushing, D. A. and Tewksbury, D. A. (1988) Doxorubicin clearance in the obese. J. Clin. Oncol. 6, 1321-1327.
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.
60. Santi, D. V., McHenry, C. S. and Sommer, H. (1974) Mechanism of interaction of thymidylate synthetase with 5-fluorodeoxyuridylate. Biochemistry 13, 471-481.
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.
62. Schmetzer, O. and Flörcken, 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
65. Siegel, R. L., Miller, K. D. and Jemal, A. (2017) Cancer statistics, 2017. CA Cancer J. Clin. 67, 7-30.
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 fluo-rouracil-based chemotherapy for colorectal cancer. J. Clin. Oncol. 20, 1491-1498.
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 predic-tors of 5-fluorouracil toxicity. Analysis of a large scale phase III trial. Cancer 75, 11-17.
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.
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 doxo-rubicinol in cardiac tissue of mice lacking mdr1a P-glycoprotein. Br. J. Cancer 79, 108-113.
72. Wang, J. and Huang, Y. (2007) Pharmacogenomics of sex difference in chemotherapeutic toxicity. Curr. Drug Discov. Technol. 4, 59-68.
73. Wasternack, C. (1980) Degradation of pyrimidines and pyrimidine analogs--pathways and mutual influences. Pharmacol. Ther. 8, 629-651.
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.
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.
77. Yoshioka, A., Tanaka, S., Hiraoka, O., Koyama, Y., Hirota, Y., Ayusawa, D., Seno, T., Garrett, C. and Wataya, Y. (1987) Deoxyribonucleo-side 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.
79. Zucker, I. and Beery, A. K. (2010) Males still dominate animal studies. Nature 465, 690.