Uncovering the epidemiology of bladder cancer in the Arab world: A review of risk factors, molecular mechanisms, and clinical features
Noura F. Abbasa*(),Marc R. Aoudea,Hampig R. Kouriea,Humaid O. Al-Shamsibcdef
aDepartment of Hematology-Oncology, Hotel Dieu De France Hospital, Saint Joseph University of Beirut, Riad El Solh, Lebanon bDepartment of Oncology, Burjeel Cancer Institute, Burjeel Medical City, Abu Dhabi, United Arab Emirates cInnovation and Research Center, Burjeel Cancer Institute, Burjeel Medical City, Abu Dhabi, United Arab Emirates dCollege of Medicine, University of Sharjah, Sharjah, United Arab Emirates eEmirates Oncology Society, Dubai, United Arab Emirates fCollege of Medicine, Gulf Medical University, Ajman, United Arab Emirates
Objective: Bladder cancer (BC) is a significant public health concern in the Middle East and North Africa, but the epidemiology and clinicopathology of the disease and contributors to high mortality in this region remain poorly understood. The aim of this systematic review was to investigate the epidemiological features of BC in the Arab world and compare them to those in Western countries in order to improve the management of this disease.
Methods: An extensive electronic search of the PubMed/PMC and Cochrane Library databases was conducted to identify all articles published until May 2022, following the Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines. A total of 95 articles were included in the final analysis after title, abstract, and full-text screening, with additional data obtained from the GLOBOCAN and WHO 2020 databases.
Results: Most of the included articles were case-control studies examining the risk factors and molecular mechanisms of BC. These studies originated from 10 different countries, with Egypt being the most active contributor. While BC in the Arab world shares some common risk factors with Western countries, such as smoking and occupational exposure, it also exhibits unique features related to schistosomiasis. The high mortality rates in this region are alarming and can be attributed to various factors, including the prevalence of smoking, the impact of schistosomiasis, a combination of genetic and socioeconomic factors, treatment shortages, and limited access to care or inadequate assessment of the quality of care.
Conclusion: Despite the relatively low incidence of BC in Arab countries, the mortality rates are among the highest worldwide. BC tends to be more aggressive in the Arab world, making it essential to implement strategies to address this burden.
. [J]. Asian Journal of Urology, 2024, 11(3): 406-422.
Noura F. Abbas, Marc R. Aoude, Hampig R. Kourie, Humaid O. Al-Shamsi. Uncovering the epidemiology of bladder cancer in the Arab world: A review of risk factors, molecular mechanisms, and clinical features. Asian Journal of Urology, 2024, 11(3): 406-422.
? Increased in BC -5 folds (urinary β-glucuronidase) ? Decreased in BC -10% (urinary acid phosphatase)
urinary acid phosphatase
Khalafallah and Abul-Fadl, 1964 [70]
Egypt
BBC
Tryptophan metabolites:
? Increased in BC -8 folds (3-hydroxyanthranilic acid) -6 folds (anthranilic acid) ? Decreased in BC -50% (kynurenic acid) -50% (xanthurenic acid)
3-hydroxyanthranilic acid, anthranilic acid, kynurenic acid, and xanthurenic acid
El-Sewedy et al., 1978 [72]
Egypt
BBC
Urinary α-esterases
? Increased in BC (p<0.001); diagnostic accuracy of 95.9%
Tricker et al., 1989 [71]
Egypt
BBC
Urinary nitrate, nitrite, and N-nitroso-compounds
? Increased in BC
El-Sharkawi et al., 2014 [74]
Egypt
NA
Urinary MMP-3 and urinary MMP-9
? Increased in BC - early and late stage (urinary MMP-3) - late stage only (urinary MMP-9) ? Diagnostic accuracy of about 94% (excluding early-stage MMP-9)
Salama et al., 2012 [87]
Egypt
NA
NMP22, E-cadherin, cathepsin D
? Increased in BC ? Correlated to recurrence (NMP22 and E-cadherin)
Kapila et al., 2008 [75]
Kuwait
NA
NMP22 (with urine cytology)
? Increased sensitivity (to 96%) but decreased specificity (to 30%)
Ismail et al., 2016 [76]
Egypt
NA
mRNA-S100A genes (with urine cytology)
? Increased sensitivity (to 87%-96%)
Esawy et al., 2020 [88]
Egypt
NA
Serum irisin
? Decreased in BC (p<0.001); negative correlation with mortality and stage (p<0.001)
Mahmoud et al., 2010 [89]
Egypt
NA
Serum interleukin-8
? Increased in BC (p<0.0001); sensitivity 71%, specificity 98% for a cut-off of 35 pg/mL; invasiveness (p<0.01)
Warren et al., 1995 [54]
Egypt
BBC
p53 mutation
? Increased CpG dinucleotide transitions
Osman et al., 1997 [81]
Egypt
BBC
p53 mutation
? Invasiveness, LNI (p<0.04)
Khaled et al., 2003 [113]
Egypt
BBC
p53 mutation
? High stage and grade (p<0.0001)
Helal et al., 2006 [80]
Egypt
BBC
p53 mutation
? High grade (p=0.03)
Owyong et al., 2019 [82]
Egypt
SCC
PD-L1 negative
? High stage (p=0.04) and grade (p=0.01), LNI (p<0.01), and recurrence (p=0.03)
Moussa et al., 2009 [84]
Egypt
NA
COX2
? Increased in BC
Al-Maghrabi et al., 2019 [83]
Saudi Arabia
TCC
COX2
? High grade (p<0.001) and LNI (p=0.011)
Al-Maghrabi, 2019 [85]
Saudi Arabia
TCC
SIRT1
? Local recurrence and poor survival
Aboushousha et al., 2020 [86]
Egypt
TCC
STAT3
? High grade and muscle-invasiveness
Aly and Khaled, 2004 [90]
Egypt
BBC
HER2
? High grade (p=0.01)
Nedjadi et al., 2016 [91]
Saudi Arabia
TCC
HER2
? High stage (p=0.002) and LNI (p<0.04)
Al-Sharaky et al., 2020 [92]
Egypt
NA
ROC1, P21, and CAIX
? Invasiveness and high grade
Labban et al., 2021 [93]
Lebanon
NA
Coexpression of GATA3 and cytokeratin 5/6 or 14
? Reduced progression-free survival compared to GATA3 alone
Bodoor et al., 2010 [94]
Jordan
NA
FGF23
? Good prognosis, low stage and grade
Arab country
Prevalence of tobacco smokinga, %
Tobacco smoking ranking worldwidea
BC incidence ranking in the Arab world
BC mortality ranking in the Arab world
HDI
Algeria
21.0
#75
#7
#4
0.736 (H)
Bahrain
14.9
#99
#10
#15
0.877 (VH)
Comoros
20.3
#78
#14
#9
0.562 (M)
Djibouti
NA
NA
#19
#21
0.510 (L)
Egypt
24.3
#50
#1
#1
0.734 (H)
Iraq
18.5
#86
#11
#8
0.679 (M)
Jordan
34.8
#14
#4
#7
0.723 (H)
Kuwait
17.9
#88
#13
#16
0.822 (VH)
Lebanon
38.2
#7
#5
#6
0.726 (H)
Libya
NA
NA
#6
#3
0.703 (H)
Mauritania
10.7
#127
#20
#22
0.556 (M)
Morocco
14.5
#100
#12
#11
0.679 (M)
Oman
8.0
#144
#15
#12
0.827 (VH)
Palestine
21.2
#72
#2
#10
0.716 (H)
Qatar
11.8
#119
#16
#13
0.854 (VH)
Saudi Arabia
14.3
#105
#17
#20
0.870 (VH)
Somalia
NA
NA
#18
#17
NA
Sudan
NA
NA
#21
#18
0.510 (L)
Syria
NA
NA
#8
#5
0.577 (M)
Tunisia
24.6
#48
#3
#2
0.737 (H)
United Arab Emirates
NA
NA
#9
#14
0.912 (VH)
Yemen
20.3
#80
#22
#19
0.460 (L)
WHO region
Number of individuals receiving PC for schistosomiasis
Africa
211 470 992
Eastern Mediterranean
20 582 722
Western Pacific
2 939 845
Americas (South America)
1 620 830
South-East Asia
21 815
Europe
Not applicable
Global
236 636 204
Arab country
Schistosomiasis endemicity status
Egypta
Endemic, requiring PC
Somalia
Endemic, requiring PC
Mauritania
Endemic, requiring PC
Sudan
Endemic, requiring PC
Yemen
Endemic, requiring PC
Libyaa
Status of transmission to be determined
Syria
Status of transmission to be determined
Iraqa
Status of transmission to be determined
Oman
Status of transmission to be determined
Tunisiaa
Interruption of transmission to be confirmed
Jordana
Interruption of transmission to be confirmed
Lebanona
Interruption of transmission to be confirmed
Moroccoa
Interruption of transmission to be confirmed
Djiboutia
Interruption of transmission to be confirmed
Algeria
No PC required
Saudi Arabiaa
No PC required
Palestinea
Non-endemic
United Arab Emirates
Non-endemic
Bahrain
Non-endemic
Kuwaita
Non-endemic
Comoros
Non-endemic
Qatar
Non-endemic
[1]
Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global Cancer Statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2021; 71:209-49.
[2]
Saginala K, Barsouk A, Aluru JS, Rawla P, Padala SA, Barsouk A. Epidemiology of bladder cancer. Med Sci 2020; 8:15. https://doi.org/10.3390/medsci8010015
doi: https://doi.org/10.3390/medsci8010015
[3]
Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer statistics, 2022. CA Cancer J Clin 2022; 72:7-33.
[4]
SEERExplorer: an interactive website for SEER cancer statistics Internet. Surveillance Research Program, National Cancer Institute; 2023 Apr 19. https://seer.cancer.gov/statistics-network/explorer/. [Accessed 21 July 2023].
Zaghloul MS. Bladder cancer and schistosomiasis. J Egypt Natl Cancer Inst 2012; 24:151-9.
[7]
Mostafa MH, Sheweita SA, O’Connor PJ. Relationship between schistosomiasis and bladder cancer. Clin Microbiol Rev 1999; 12:97-111.
[8]
Babjuk M, Burger M, Capoun O, Cohen D, Compérat EM, Dominguez Escrig JL, et al. European Association of Urology guidelines on non-muscle-invasive bladder cancer (Ta, T1, and carcinoma in situ). Eur Urol 2022; 81:75-94.
[9]
Anastasiadis A, de Reijke TM. Best practice in the treatment of nonmuscle invasive bladder cancer. Ther Adv Urol 2012; 4:13-32.
Roupre?t M, Pignot G, Masson-Lecomte A, Compérat E, Audenet F, Roumiguié M, et al. [French ccAFU guidelinesdupdate 2020e2022: bladder cancer]. Prog Urol 2020; 30:S78-135. [Article in French]. https://doi.org/10.1016/S1166-7087(20)30751-X
doi: https://doi.org/10.1016/S1166-7087(20)30751-X
[12]
Bukhari N, Al-Shamsi HO, Azam F. Update on the treatment of metastatic urothelial carcinoma. Sci World J 2018; 2018:5682078. https://doi.org/10.1155/2018/5682078
doi: https://doi.org/10.1155/2018/5682078
[13]
Al-Shamsi HO, Iqbal F, Abu-Gheida IH. Cancer in the Arab world. Singapore: Springer; 2022. p. 1-6
[14]
Abdul Salam A, Elsegaey I, Khraif R, AlMutairi A, Aldosari A. Components and public health impact of population growth in the Arab world. PLoS One 2015; 10:e0124944. https://doi.org/10.1371/journal.pone.0124944
doi: https://doi.org/10.1371/journal.pone.0124944
[15]
Cumberbatch MGK, Jubber I, Black PC, Esperto F, Figueroa JD, Kamat AM, et al. Epidemiology of bladder cancer: a systematic review and contemporary update of risk factors in 2018. Eur Urol 2018; 74:784-95.
[16]
Antoni S, Ferlay J, Soerjomataram I, Znaor A, Jemal A, Bray F. Bladder cancer incidence and mortality: a global overview and recent trends. Eur Urol 2017; 71:96-108.
[17]
Richters A, Aben KKH, Kiemeney LALM. The global burden of urinary bladder cancer: an update. World J Urol 2020; 38:1895-904.
[18]
Shamseer L, Moher D, Clarke M, Ghersi D, Liberati A, Petticrew M, et al. Preferred Reporting Items for Systematic review and Meta-Analysis protocols (PRISMA-P) 2015: elaboration and explanation. BMJ 2015; 350:g7647. https://doi.org/10.1136/bmj.g7647
doi: https://doi.org/10.1136/bmj.g7647
[19]
Cancer today Internet. http://gco.iarc.fr/today/home. [Accessed 21 July 2022].
[20]
WHOjWorld Health Organization Internet. https://apps.who.int/neglected_diseases/ntddata/sch/sch.html. [Accessed 21 July 2022].
[21]
Schistosomiasis [Internet]. https://www.who.int/newsroom/fact-sheets/detail/schistosomiasis. [Accessed 21 July 2022].
[22]
International Agency for Research on Cancer. List of classifications by cancer sites with sufficient or limited evidence in humans. IARC Monographs volumes 1-134. https://monographs.iarc.who.int/wp-content/uploads/2019/07/Classifications_by_cancer_site.pdf. [Accessed 27 July 2023].
[23]
Zheng YL, Amr S, Saleh DA, Dash C, Ezzat S, Mikhail NN, et al. Urinary bladder cancer risk factors in Egypt: a multicenter case-control study. Cancer Epidemiol Biomarkers Prev 2012; 21:537-46.
[24]
Makhyoun NA. Smoking and bladder cancer in Egypt. Br J Cancer 1974; 30:577-81.
[25]
Amr S, Dawson R, Saleh DA, Magder LS, Mikhail NN, St George DM, et al. Agricultural workers and urinary bladder cancer risk in Egypt. Arch Environ Occup Health 2014; 69:3-10.
[26]
Feki-Tounsi M, Olmedo P, Gil F, Khlifi R, Mhiri MN, Rebai A, et al. Cadmium in blood of Tunisian men and risk of bladder cancer: interactions with arsenic exposure and smoking. Environ Sci Pollut Res Int 2013; 20:7204-13.
[27]
Feki-Tounsi M, Olmedo P, Gil F, Khlifi R, Mhiri MN, Rebai A, et al. Low-level arsenic exposure is associated with bladder cancer risk and cigarette smoking: a case-control study among men in Tunisia. Environ Sci Pollut Res Int 2013; 20:3923-31.
[28]
Felix AS, Soliman AS, Khaled H, Zaghloul MS, Banerjee M, El- Baradie M, et al. The changing patterns of bladder cancer in Egypt over the past 26 years. Cancer Causes Control 2008; 19:421-9.
[29]
Fedewa SA, Soliman AS, Ismail K, Hablas A, Seifeldin IA, Ramadan M, et al. Incidence analyses of bladder cancer in the Nile delta region of Egypt. Cancer Epidemiol 2009; 33:176-81.
[30]
Salem HK, Mahfouz S. Changing patterns (age, incidence, and pathologic types) of schistosoma-associated bladder cancer in Egypt in the past decade. Urology 2012; 79:379-83.
[31]
Bedwani R, Renganathan E, El Kwhsky F, Braga C, Abu Seif HH, Abul Azm T, et al. Schistosomiasis and the risk of bladder cancer in Alexandria, Egypt. Br J Cancer 1998; 77:1186-9.
[32]
Lakkis NA, Adib SM, Hamadeh GN, El-Jarrah RT, Osman MH. Bladder cancer in Lebanon: incidence and comparison to regional and Western countries. Cancer Control 2018; 25:1073274818789359. https://doi.org/10.1177/1073274818789359
doi: https://doi.org/10.1177/1073274818789359
[33]
Wolpert BJ, Amr S, Ezzat S, Saleh D, Gouda I, Loay I, et al. Estrogen exposure and bladder cancer risk in Egyptian women. Maturitas 2010; 67:353-7.
[34]
Jackson SS, St George DM, Loffredo CA, Amr S. Nonoccupational exposure to agricultural work and risk of urinary bladder cancer among Egyptian women. Arch Environ Occup Health 2017; 72:166-72.
[35]
Zarzour AH, Selim M, Abd-Elsayed AA, Hameed DA, Abdelaziz MA. Muscle invasive bladder cancer in Upper Egypt: the shift in risk factors and tumor characteristics. BMC Cancer 2008; 8:250. https://doi.org/10.1186/1471-2407-8-250
doi: https://doi.org/10.1186/1471-2407-8-250
pmid: 18759990
[36]
Feki-Tounsi M, Khlifi R, Louati I, Fourati M, Mhiri MN, Hamza- Chaffai A, et al. Polymorphisms in XRCC1, ERCC2, and ERCC3 DNA repair genes, CYP1A1 xenobiotic metabolism gene, and tobacco are associated with bladder cancer susceptibility in Tunisian population. Environ Sci Pollut Res Int 2017; 24:22476-84.
[37]
Goerlitz D, Amr S, Dash C, Saleh DA, El Daly M, Abdel- Hamid M, et al. Genetic polymorphisms in NQO1 and SOD2: interactions with smoking, schistosoma infection, and bladder cancer risk in Egypt. Urol Oncol 2014; 32:47.e15-20. https://doi.org/10.1016/j.urolonc.2013.06.016
doi: https://doi.org/10.1016/j.urolonc.2013.06.016
[38]
Amr S, Dawson R, Saleh DA, Magder LS, St George DM, El- Daly M, et al. Pesticides, gene polymorphisms, and bladder cancer among Egyptian agricultural workers. Arch Environ Occup Health 2015; 70:19-26.
[39]
Hameed DA, Yassa HA, Agban MN, Hanna RT, Elderwy AM, Zwaita MA. Genetic aberrations of the K-ras proto-oncogene in bladder cancer in relation to pesticide exposure. Environ Sci Pollut Res Int 2018; 25:21535-42.
[40]
Khedhiri S, Stambouli N, Ouerhani S, Rouissi K, Marrakchi R, Gaaied AB, et al. The impact of smoking and polymorphic enzymes of xenobiotic metabolism on the stage of bladder tumors: a generalized ordered logistic regression analysis. J Cancer Res Clin Oncol 2010; 136:1111-6.
[41]
El Desoky ES, AbdelSalam YM, Salama RH, El Akkad MA, Atanasova S, von Ahsen N, et al. NAT2)5/)5 genotype (341T>C) is a potential risk factor for schistosomiasisassociated bladder cancer in Egyptians. Ther Drug Monit 200; 27:297-304.
[42]
Rouissi K, Ouerhani S, Marrakchi R, Ben Slama MR, Sfaxi M, Ayed M, et al. Combined effect of smoking and inherited polymorphisms in arylamine N-acetyltransferase 2, glutathione S-transferases M1 and T1 on bladder cancer in a Tunisian population. Cancer Genet Cytogenet 2009; 190:101-7.
[43]
Rouissi K, Ouerhani S, Hamrita B, Bougatef K, Marrakchi R, Cherif M, et al. Smoking and polymorphisms in xenobiotic metabolism and DNA repair genes are additive risk factors affecting bladder cancer in Northern Tunisia. Pathol Oncol Res 2011; 17:879-86.
[44]
Rouissi K, Bahria IB, Bougatef K, Marrakchi R, Stambouli N, Hamdi K, et al. The effect of tobacco, XPC, ERCC2 and ERCC5 genetic variants in bladder cancer development. BMC Cancer 2011; 11:101. https://doi.org/10.1186/1471-2407-11-101
doi: https://doi.org/10.1186/1471-2407-11-101
[45]
Lafuente A, Zakahary MM, el-Aziz MA, Ascaso C, Lafuente MJ, Trias M, et al. Influence of smoking in the glutathione-Stransferase M1 deficiencydassociated risk for squamous cell carcinoma of the bladder in schistosomiasis patients in Egypt. Br J Cancer 1996; 74:836-8.
[46]
Ghazaly GE, Zakahary MM, el-Aziz MA, Mahmoud AA, Carretero P, Lafuente A. Expression of glutathione S-transferase activity and glutathione content in squamous cell carcinoma of bladder associated with schistosomiasis in a population in Egypt. Scand J Urol Nephrol 1997; 31:43-7.
[47]
Ouerhani S, Rouissi K, Marrakchi R, Ben Slama MR, Sfaxi M, Chebil M, et al. Combined effect of NAT2, MTR and MTHFR genotypes and tobacco on bladder cancer susceptibility in Tunisian population. Cancer Detect Prev 2009; 32:395-402.
[48]
Ouerhani S, Oliveira E, Marrakchi R, Ben Slama MR, Sfaxi M, Ayed M, et al. Methylenetetrahydrofolate reductase and methionine synthase polymorphisms and risk of bladder cancer in a Tunisian population. Cancer Genet Cytogenet 2007; 176:48-53.
[49]
Abdel-Haleem AM, El-Zeiry MI, Mahran LG, Abou-Aisha K, Rady MH, Rohde J, et al. Expression of RFC/SLC19A 1 is associated with tumor type in bladder cancer patients. PLoS One 2011; 6:e21820. https://doi.org/10.1371/journal.pone.0021820
doi: https://doi.org/10.1371/journal.pone.0021820
[50]
Kobeissi LH, Yassine IA, Jabbour ME, Moussa MA, Dhaini HR. Urinary bladder cancer risk factors: a Lebanese case-control study. Asian Pac J Cancer Prev 2013; 14:3205-11.
[51]
Wolpert BJ, Amr S, Saleh DA, Ezzat S, Gouda I, Loay I, et al. Associations differ by sex for catechol-O-methyltransferase genotypes and bladder cancer risk in South Egypt. Urol Oncol 2012; 30:841-7.
[52]
Ben Wafi S, Kallel A, Ben Fradj MK, Sallemi A, Ben Rhouma S, Ben Halima M, et al. Haplotype-based association of vascular endothelial growth factor gene polymorphisms with urothelial bladder cancer risk in Tunisian population. J Clin Lab Anal 2018; 32:e22610. https://doi.org/10.1002/jcla.22610
doi: https://doi.org/10.1002/jcla.22610
[53]
Al-Abbasi DS, Al-Janabi AA, Al-Toriahi KM, Jabor TA, Yasseen AA. Expression of VEGF in urinary bladder transitional cell carcinoma in an Iraqi population subjected to depleted uranium: an immunohistochemical study. Appl Immunohistochem Mol Morphol 2009; 17:307-11.
[54]
Warren W, Biggs PJ, el-Baz M, Ghoneim MA, Stratton MR, Venitt S. Mutations in the p53 gene in schistosomal bladder cancer: a study of 92 tumours from Egyptian patients and a comparison between mutational spectra from schistosomal and non-schistosomal urothelial tumours. Carcinogenesis 1995; 16:1181-9.
[55]
Gutiérrez MI, Siraj AK, Khaled H, Koon N, El-Rifai W, Bhatia K. CpG island methylation in Schistosoma- and non- Schistosoma-associated bladder cancer. Mod Pathol 2004; 17:1268-74.
[56]
Feki-Tounsi M, Khlifi R, Mhiri MN, Rebai A, Hamza-Chaffai A. Cytogenetic damage in the oral mucosa cells of bladder cancer patients exposed to tobacco in Southern Tunisia. Environ Sci Pollut Res Int 2014; 21:12922-7.
[57]
Wang H, Wang Y, Kota KK, Kallakury B, Mikhail NN, Sayed D, et al. Strong association between long and heterogeneous telomere length in blood lymphocytes and bladder cancer risk in Egyptian. Carcinogenesis 2015; 36:1284-90.
[58]
Wang H, Wang Y, Kota KK, Sun B, Kallakury B, Mikhail NN, et al. Strong associations between chromosomal aberrations in blood lymphocytes and the risk of urothelial and squamous cell carcinoma of the bladder. Sci Rep 2017; 7:13493. https://doi.org/10.1038/s41598-017-13976-y
doi: https://doi.org/10.1038/s41598-017-13976-y
pmid: 29044177
[59]
Shaw ME, Elder PA, Abbas A, Knowles MA. Partial allelotype of schistosomiasis-associated bladder cancer. Int J Cancer 1999; 80:656-61.
[60]
Aly MS, Khaled HM. Chromosomal aberrations in bilharzial bladder cancer as detected by fluorescence in situ hybridization. Cancer Genet Cytogenet 1999; 114:62-7.
[61]
Khaled HM, Aly MS, Magrath IT. Loss of Y chromosome in bilharzial bladder cancer. Cancer Genet Cytogenet 2000; 117:32-6.
[62]
Aly MS, Khaled HM. Chromosomal aberrations in early-stage bilharzial bladder cancer. Cancer Genet Cytogenet 2002; 132:41-5.
[63]
Tamimi Y, Bringuier PP, Smit F, van Bokhoven A, Abbas A, Debruyne FM, et al. Homozygous deletions of p16INK4 occur frequently in bilharziasis-associated bladder cancer. Int J Cancer 1996; 68:183-7.
[64]
Shams TM, Metawea M, Salim EI. c-KIT positive Schistosomal urinary bladder carcinoma are frequent but lack KIT gene mutations. Asian Pac J Cancer Prev 2013; 14:15-20.
[65]
El-Boulkany MN, Ghoneim MA, Mansour MA. Carcinoma of the bilharzial bladder in Egypt. Clinical and pathological features.. Br J Urol 1972; 44:561-70.
[66]
El-Siddig AA, Albasri AM, Hussainy AS, Alhujaily AS. Urinary bladder cancer in adults: a histopathological experience from Madinah, Saudi Arabia. J Pakistan Med Assoc 2017; 67:83-6.
[67]
Alghafees MA, Alqahtani MA, Musalli ZF, Alasker A. Bladder cancer in Saudi Arabia: a registry-based nationwide descriptive epidemiological and survival analysis. Ann Saudi Med 2022; 42:17-28.
[68]
Saheb Sharif-Askari N, Bendardaf R, Saheb Sharif-Askari F, El Tabbal AM, El Ayan MA. Incidence of bladder cancer in Benghazi, Libya over the past three decades. Sci Rep 2018; 8:10822. https://doi.org/10.1038/s41598-018-29187-y
doi: https://doi.org/10.1038/s41598-018-29187-y
pmid: 30018344
[69]
Abul-Fadl MA, Metwalli OM. Studies on certain urinary and blood serum enzymes in bilharziasis and their possible relation to bladder cancer in Egypt. Br J Cancer 1963; 17:137-41.
[70]
Khalafallah AS, Abul-Fadl MA. Studies on the urinary excretion of certain tryptophan metabolites before and after tryptophan loading dose in bilharziasis, bilharzial bladder cancer and certain other types of malignancies in Egypt. Br J Cancer 1964; 13:592-604.
[71]
Tricker AR, Mostafa MH, Spiegelhalder B, Preussmann R. Urinary excretion of nitrate, nitrite and N-nitroso compounds in schistosomiasis and bilharzia bladder cancer patients. Carcinogenesis 1989; 10:547-52.
[72]
El-Sewedy SM, Arafa A, Abdel-Aal G, Mostafa MH. The activities of urinary alpha-esterases in bilharziasis and their possible role in the diagnosis of bilharzial bladder cancer in Egypt. Trans R Soc Trop Med Hyg 1978; 72:525-8.
[73]
Alsabti EA. Serum alphafetoprotein in bladder carcinoma. Oncology 1977; 34:78-9.
[74]
El-Sharkawi F, El Sabah M, Hassan Z, Khaled H. The biochemical value of urinary metalloproteinases 3 and 9 in diagnosis and prognosis of bladder cancer in Egypt. J Biomed Sci 2014; 21:72. https://doi.org/10.1186/s12929-014-0072-4
doi: https://doi.org/10.1186/s12929-014-0072-4
[75]
Kapila K, Kehinde EO, Anim JT, Mojiminiyi OA, Vinsu A, George SS, et al. Could nuclear matrix protein 22 (NMP22) play a role with urine cytology in screening for bladder cancer? dexperience at Kuwait University. Cytopathology 2008; 19:369-74.
[76]
Ismail MF, El Boghdady NA, Shabayek MI, Awida HA, Abozeed H. Evaluation and screening of mRNA S100A genes as serological biomarkers in different stages of bladder cancer in Egypt. Tumour Biol 2016; 37:4621-31.
[77]
Mokhtar A, Al MM, Al WM, Othman KA, Kattan SA, Al MF. Is survival after radical cystectomy for bladder cancer in Saudi patients different from that of Western patients? Ann Saudi Med 2017; 37:194-200.
[78]
Spradling K, Lotan Y, Shokeir A, Abol-Enein H, Mosbah A, Morgan JB, et al. Lymphovascular invasion is associated with oncologic outcomes following radical cystectomy for squamous cell carcinoma of the urinary bladder. Urol Oncol 2016; 34:417.e1-8. https://doi.org/10.1016/j.urolonc.2016.03.023
doi: https://doi.org/10.1016/j.urolonc.2016.03.023
[79]
Khaled H, El Hattab O, Moneim DA, Kassem HA, Morsi A, Sherif G, et al. A prognostic index (bladder prognostic index) for bilharzial-related invasive bladder cancer. Urol Oncol 2005; 23:254-60.
[80]
Helal TEA, Fadel MT, El-Sayed NK. Human papilloma virus and p53 expression in bladder cancer in Egypt: relationship to schistosomiasis and clinicopathologic factors. Pathol Oncol Res 2006; 12:173-8.
[81]
Osman I, Scher HI, Zhang ZF, Pellicer I, Hamza R, Eissa S, et al. Alterations affecting the p53 control pathway in bilharzialrelated bladder cancer. Clin Cancer Res 1997; 3:531-6.
[82]
Owyong M, Lotan Y, Kapur P, Panwar V, McKenzie T, Lee TK, et al. Expression and prognostic utility of PD-L1 in patients with squamous cell carcinoma of the bladder. Urol Oncol 2019; 37:478-84.
[83]
Al-Maghrabi B, Gomaa W, Abdelwahed M, Al-Maghrabi J. Increased COX-2 Immunostaining in urothelial carcinoma of the urinary bladder is associated with invasiveness and poor prognosis. Anal Cell Pathol 2019; 2019:5026939. https://doi.org/10.1155/2019/5026939
doi: https://doi.org/10.1155/2019/5026939
[84]
Moussa M, Omran Z, Nosseir M, Lotfy A, Swellam T. Cyclooxygenase-2 expression on urothelial and inflammatory cells of cystoscopic biopsies and urine cytology as a possible predictive marker for bladder carcinoma. APMIS 2009; 117:45-52.
[85]
Al-Maghrabi JA. Overexpression of SIRT1 in urothelial carcinoma of the urinary bladder is associated with local recurrence and poor survival. Saudi Med J 2019; 40:541-7.
[86]
Aboushousha T, Hammam O, Aref A, Kamel A, Badawy M, Abdel Hamid A. Tissue profile of CDK4 and STAT3 as possible innovative therapeutic targets in urinary bladder cancer. Asian Pac J Cancer Prev 2020; 21:547-54.
[87]
Salama RHM, Selem TH, Elhagagy AEA, El-Gammal M, Bakar SM. Urinary tumor marker in bladder carcinoma in Upper Egypt, correlations with different clinicopathological features. Saudi J Kidney Dis Transpl 2012; 23:1068-73.
[88]
Esawy MM, Abdel-Samd KM. The diagnostic and prognostic roles of serum irisin in bladder cancer. Curr Probl Cancer 2020; 44:100529. https://doi.org/10.1016/j.currproblcancer.2019.100529
doi: https://doi.org/10.1016/j.currproblcancer.2019.100529
[89]
Mahmoud MA, Ali MH, Hassoba HM, Elhadidy GS. Serum interleukin-8 and insulin like growth factor-1 in Egyptian bladder cancer patients. Cancer Biomark 2010; 6:105-10.
[90]
Aly MS, Khaled HM. Detection of C-erb B2 gene amplification in bilharzial associated bladder cancer using fluorescence in situ hybridization. Urol Oncol 2004; 22:448-52.
[91]
Nedjadi T, Al-Maghrabi J, Assidi M, Dallol A, Al-Kattabi H, Chaudhary A, et al. Prognostic value of HER2 status in bladder transitional cell carcinoma revealed by both IHC and BDISH techniques. BMC Cancer 2016; 16:653. https://doi.org/10.1186/s12885-016-2703-5
doi: https://doi.org/10.1186/s12885-016-2703-5
pmid: 27539085
[92]
Al-Sharaky DR, Kandil MAEH, Aiad HAS, El-Hosary EM, Alagizy HA, Elshenawy MAS, et al. ROC-1, P21 and CAIX as markers of tumor aggressiveness in bladder carcinoma in Egyptian patients. Diagn Pathol 2020; 15:33. https://doi.org/10.1186/s13000-020-00947-7
doi: https://doi.org/10.1186/s13000-020-00947-7
[93]
Labban M, Najdi J, Mukherji D, Abou-Kheir W, Tabbarah A, El- Hajj A. Triple-marker immunohistochemical assessment of muscle-invasive bladder cancer: is there prognostic significance? Cancer Rep (Hoboken) 2021; 4:e1313. https://doi.org/10.1002/cnr2.1313
doi: https://doi.org/10.1002/cnr2.1313
pmid: 33538412
[94]
Bodoor K, Ghabkari A, Jaradat Z, Alkhateeb A, Jaradat S, Al-Ghazo MA, et al. FGFR3 mutational status and protein expression in patients with bladder cancer in a Jordanian population. Cancer Epidemiol 2010; 34:724-32.
[95]
Martin JW, Vernez SL, Lotan Y, Abdelhalim A, Dutta R, Shokeir A, et al. Pathological characteristics and prognostic indicators of different histopathological types of urinary bladder cancer following radical cystectomy in a large singlecenter Egyptian cohort. World J Urol 2018; 36:1835-43.
[96]
Ayedi I, Abdelli I, Chaabouni H, Charfi S, Khanfir A, Toumi N, et al. [Neuroendocrine carcinoma of the bladder: a single centre retrospective study]. Cancer Radiother 2016; 20:1-5. [Article in French].
[97]
Avitan O, Bahouth Z, Halachmi S, Shprits S, Masarwa I, Sabo E, et al. Histopathologic differences between Jewish and Arab population in Israel at first-time presentation with bladder cancer. BioMed Res Int 2017; 2017:8239601. https://doi.org/10.1155/2017/8239601
doi: https://doi.org/10.1155/2017/8239601
[98]
Alshyarba MH, Alamri A, Assiri AA. Economic impacts of the Bacillus Calmette-Guérin (BCG) therapy shortage and the proposed solutions for patients with non-muscle invasive bladder Cancer in Aseer Province, Saudi Arabia. J Fam Med Prim Care 2020; 9:2758-62.
[99]
Wong MCS, Fung FDH, Leung C, Cheung WWL, Goggins WB, Ng CF. The global epidemiology of bladder cancer: a joinpoint regression analysis of its incidence and mortality trends and projection. Sci Rep 2018; 8:1129. https://doi.org/10.1038/s41598-018-19199-z
doi: https://doi.org/10.1038/s41598-018-19199-z
pmid: 29348548
[100]
The burden of bladder cancer in the Middle East Internet. Middle East Medical Portal; 2018. http://www.middleeastmedicalportal.com/the-burden-of-bladder-cancer-in-themiddle-east/. [Accessed 22 July 2022].
[101]
Kourie HR, Haddad LE, Chouery E, Mehawej C, Jalkh N, Kassis M, et al. Genetic susceptibility to bladder cancer in a cohort of 51 Lebanese patients [Internet]. https://www.researchsquare.com/article/rs-1669372/v1. [Accessed 22 July 2022].
[102]
Zhai M, Tang C, Li M, Chen X, Jin Y, Ying X, et al. Short-term mortality risks among patients with non-metastatic bladder cancer. BMC Cancer 2020; 20:1148. https://doi.org/10.1186/s12885-020-07655-x
doi: https://doi.org/10.1186/s12885-020-07655-x
pmid: 33238972
[103]
Jabra E, Al-Omari A, Haddadin F, Alam W, Ammar K, Charafeddine M, et al. Waterpipe Smoking among bladder cancer patients: a cross-sectional study of Lebanese and Jordanian populations. J Smok Cessat 2021; 2021:6615832. https://doi.org/10.1155/2021/6615832
doi: https://doi.org/10.1155/2021/6615832
[104]
Dai X, Gakidou E, Lopez AD. Evolution of the global smoking epidemic over the past half century: strengthening the evidence base for policy action. Tob Control 2022; 31:129-37.
[105]
Matalka I, Bani-Hani K, Shotar A, Bani Hani O, Bani-Hani I. Transitional cell carcinoma of the urinary bladder: a clinicopathological study. Singapore Med J 2008; 49:790e4.
[106]
2023 World Population by Country (Live) [Internet]. https://worldpopulationreview.com/#. [Accessed 25 July 2022].
[107]
Arora S, Keeley J, Patel A, Eleswarapu SV, Bronkema C, Alanee S, et al. Defining a “high volume” radical cystectomy hospital: where do we draw the line? Eur Urol Focus 2020; 6:975-81.
[108]
Leow JJ, Catto JWF, Efstathiou JA, Gore JL, Hussein AA, Shariat SF, et al. Quality indicators for bladder cancer services: a collaborative review. Eur Urol 2020; 78:43-59.
[109]
Souaid T, Hindy JR, Eid R, Kourie HR, Kattan J. Bladder cancer knowledge in the Lebanese population: when ignorance could be harmful. Bull Cancer 2018; 105:857-61.
[110]
Zaghloul MS, Awwad HK, Akoush HH, Omar S, Soliman O, el Attar el Attar. Postoperative radiotherapy of carcinoma in bilharzial bladder: improved disease free survival through improving local control. Int J Radiat Oncol Biol Phys 1992; 23:511e7.
[111]
Attallah AM, el-Didi M, Seif F, el-Mohamady H, Dalbagni G. Comparative study between cytology and dot-ELISA for early detection of bladder cancer. Am J Clin Pathol 1996; 105:109-14.
[112]
Ali-el-Dein B, el-Baz M, Aly AN, Shamaa S, Ashamallah A. Intravesical epirubicin versus doxorubicin for superficial bladder tumors (stages pTa and pT1): a randomized prospective study. J Urol 1997; 158:68e73;discussion 73-74.
[113]
Khaled HM, Bahnassi AA, Zekri ARN, Kassem HA, Mokhtar N. Correlation between p53 mutations and HPV in bilharzial bladder cancer. Urol Oncol 2003; 21:334-41.
[114]
Ali-El-Dein B, Sarhan O, Hinev A, Ibrahiem EHI, Nabeeh A, Ghoneim MA. Superficial bladder tumours: analysis of prognostic factors and construction of a predictive index. BJU Int 2003; 92:393e9.
[115]
Khafagy M, Shaheed FA, Moneim TA. Ileocaecal vs. ileal neobladder after radical cystectomy in patients with bladder cancer: a comparative study. BJU Int 2006; 97:799-804.
[116]
Badawi H, Ahmed H, Ismail A, Diab M, Moubarak M, Badawy A, et al. Role of human papillomavirus types 16, 18, and 52 in recurrent cystitis and urinary bladder cancer among Egyptian patients. Medscape J Med 2008; 10:232. PMID: 19099026.
[117]
Osman Y, Abol-Enein H, El-Mekresh M, Gad H, Elhefnawy A, Ghoneim M. Comparison between a serous-lined extramural tunnel and T-limb ileal procedure as an antireflux technique in orthotopic ileal substitutes: a prospective randomized trial. BJU Int 2009; 104:1518-21.
[118]
Zaghloul MS, Boutrus R, El-Hossieny H, Kader YA, El-Attar I, Nazmy M. A prospective, randomized, placebo-controlled trial of zoledronic acid in bony metastatic bladder cancer. Int J Clin Oncol 2010; 15:382e9.
[119]
Goerlitz D, El Daly M, Abdel-Hamid M, Saleh DA, Goldman L, El Kafrawy S, et al. GSTM1, GSTT1 null variants, and GPX1 single nucleotide polymorphism are not associated with bladder cancer risk in Egypt. Cancer Epidemiol Biomark Prev 2011; 20:1552e4.
[120]
El-Monim HA, El-Baradie MM, Younis A, Ragab Y, Labib A. El- Attar I. A prospective randomized trial for postoperative vs. preoperative adjuvant radiotherapy for muscle-invasive bladder cancer. Urol Oncol 2013; 31:359-65.
[121]
Harraz AM, Mosbah A, Abdel-Latif M, El-Assmy A, Gad H, Shaaban AA. Impact of the type of ureteroileal anastomosis on renal function measured by diuretic scintigraphy: longterm results of a prospective randomized study. BJU Int 2014; 114:202e9.
[122]
Khaled HM, Shafik HE, Zabhloul MS, Ghoneim M, Saber RA, Manie M, et al. Gemcitabine and cisplatin as neoadjuvant chemotherapy for invasive transitional and squamous cell carcinoma of the bladder: effect on survival and bladder preservation. Clin Genitourin Cancer 2014; 12:e233-40. https://doi.org/10.1016/j.clgc.2014.04.002
doi: https://doi.org/10.1016/j.clgc.2014.04.002
[123]
Haggag R, Farag K, Abu-Taleb F, Shamaa S, Zekri AR, Elbolkainy T, et al. Low-dose versus standard-dose gemcitabine infusion and cisplatin for patients with advanced bladder cancer: a randomized phase II trial-an update. Med Oncol 2014; 31:811. https://doi.org/10.1007/s12032-013-0811-5
doi: https://doi.org/10.1007/s12032-013-0811-5
pmid: 24338168
[124]
Harraz AM, El-Shabrawy M, El-Nahas AR, El-Kappany H, Osman Y. Single versus maintenance intravesical chemotherapy for the prevention of bladder recurrence after radical nephroureterectomy for upper tract urothelial carcinoma: a randomized clinical trial. Clin Genitourin Cancer 2019; 17:e1108-15. https://doi.org/10.1016/j.clgc.2019.07.019
doi: https://doi.org/10.1016/j.clgc.2019.07.019
[125]
Ben Selma W, Ziadi S, Ben Gacem R, Amara K, Ksiaa F, Hachana M, et al. Investigation of human papillomavirus in bladder cancer in a series of Tunisian patients. Pathol Res Pract 2010; 206:740e3.
[126]
Hadami K, Dakka N, Bensaid M, El Ahanidi H, Ameur A, Chahdi H, et al. Evaluation of glutathione S-transferase pi 1 expression and gene promoter methylation in Moroccan patients with urothelial bladder cancer. Mol Genet Genomic Med 2018; 6:819-27.
[127]
Bani-Hani M, Abdel Majid A, Al-Zubi MT, Al Demour S, Al Zoubi MS, Abuhamad M, et al. Continuous saline bladder irrigation in reducing recurrence and progression when compared to immediate mitomycin-C instillation postresection of bladder tumor: a short communication. Asian Pac J Cancer Prev 2022; 23:171e5.
[128]
Monitoring tobacco use and prevention policies Internet. https://www.who.int/data/gho/data/indicators/indicatordetails/GHO/gho-tobacco-control-monitori-tobacco-useand-prevention-policies. [Accessed 25 June 2022].
[129]
Jones TD, Cheng L. Histologic grading of bladder tumors: using both the 1973 and 2004/2016 World Health Organization Systems in combination provides valuable information for establishing prognostic risk groups. Eur Urol 2021; 79:489-91.
