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http://dx.doi.org/10.4062/biomolther.2018.103

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)
Publication Information
Biomolecules & Therapeutics / v.26, no.4, 2018 , pp. 335-342 More about this Journal
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
Sex Difference; Cancer; Sex hormone; Chemotherapy;
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1 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.   DOI
2 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.
3 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.   DOI
4 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.   DOI
5 Jordan, M. A. and Wilson. (2004) Microtubules as a target for anticancer drugs. Nat. Rev. Cancer 4, 253-265.   DOI
6 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.
7 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.   DOI
8 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.   DOI
9 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.   DOI
10 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.   DOI
11 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.
12 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.   DOI
13 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.   DOI
14 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.   DOI
15 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.   DOI
16 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.   DOI
17 Wang, J. and Huang, Y. (2007) Pharmacogenomics of sex difference in chemotherapeutic toxicity. Curr. Drug Discov. Technol. 4, 59-68.   DOI
18 Wasternack, C. (1980) Degradation of pyrimidines and pyrimidine analogs--pathways and mutual influences. Pharmacol. Ther. 8, 629-651.   DOI
19 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.
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.   DOI
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.   DOI
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.   DOI
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.   DOI
24 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.   DOI
25 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.   DOI
26 Ferrara, N. (2004) Vascular endothelial growth factor: basic science and clinical progress. Endocr. Rev. 25, 581-611.   DOI
27 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.   DOI
28 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.
29 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.   DOI
30 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.   DOI
31 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.   DOI
32 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.   DOI
33 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.   DOI
34 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.   DOI
35 Mader, R. M. (2007) The potential of gender-specific tumor pharmacology. Pharmacogenomics 8, 271-274.   DOI
36 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.   DOI
37 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.   DOI
38 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.   DOI
39 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.   DOI
40 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.   DOI
41 Mannervik, B. and Danielson, U. H. (1988) Glutathione transferases--structure and catalytic activity. CRC Crit. Rev. Biochem. 23, 283-337.   DOI
42 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.
43 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.   DOI
44 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.   DOI
45 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.   DOI
46 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.
47 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.   DOI
48 Zucker, I. and Beery, A. K. (2010) Males still dominate animal studies. Nature 465, 690.   DOI
49 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.   DOI
50 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.   DOI
51 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.   DOI
52 Bren, L. (2005) Does sex make a difference? F.D.A. Consum. 39, 10-15.
53 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.   DOI
54 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.   DOI
55 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.   DOI
56 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.   DOI
57 Mitry, M. A. and Edwards, J. G. (2016) Doxorubicin induced heart failure: phenotype and molecular mechanisms. Int. J. Cardiol. Heart Vasc. 10,17-24.
58 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.   DOI
59 Rademaker, M. (2001) Do women have more adverse drug reactions? Am. J. Clin. Dermatol. 2, 349-351.   DOI
60 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.   DOI
61 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.   DOI
62 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.   DOI
63 Rivankar, S. (2014) An overview of doxorubicin formulations in cancer therapy. J. Cancer Res. Ther. 10, 853-858.   DOI
64 Diasio, R. B. and Harris, B. E. (1989) Clinical pharmacology of 5-fluorouracil. Clin. Pharmacokinet. 16, 215-237.   DOI
65 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.   DOI
66 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.   DOI
67 Dorak, M. T. and Karpuzoglu, E. (2012) Gender differences in cancer susceptibility: an inadequately addressed issue. Front Genet. 3, 268.
68 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.   DOI
69 Hayes, J. D. and Strange, R. C. (2000) Glutathione S-transferase polymorphisms and their biological consequences. Pharmacology 61, 154-166.   DOI
70 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.   DOI
71 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.   DOI
72 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.   DOI
73 Rodvold, K. A., Rushing, D. A. and Tewksbury, D. A. (1988) Doxorubicin clearance in the obese. J. Clin. Oncol. 6, 1321-1327.   DOI
74 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.   DOI
75 Santi, D. V., McHenry, C. S. and Sommer, H. (1974) Mechanism of interaction of thymidylate synthetase with 5-fluorodeoxyuridylate. Biochemistry 13, 471-481.   DOI
76 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.
77 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.
78 Siegel, R. L., Miller, K. D. and Jemal, A. (2016) Cancer statistics, 2016. CA Cancer J. Clin. 66, 7-30   DOI
79 Siegel, R. L., Miller, K. D. and Jemal, A. (2017) Cancer statistics, 2017. CA Cancer J. Clin. 67, 7-30.   DOI