Geographic distribution and risk of upper urothelial carcinomas in Croatia, 2001–2011

Abstract

Background Strong associations exist between Balkan endemic nephropathy (BEN) and upper urothelial carcinomas (UUCs). However, the common etiology between the two remains unclear and there are no studies to date that visualize UUC risks in Croatia. In Croatia, 14 villages in the southwestern part of Brod-Posavina County are considered endemic for BEN. The aim of this ecological study is to map cancer risks and describe the case distribution of UUCs in Croatia at the county level during 2001–2011. Methods A total of 608 incident cases from the Croatian National Cancer Registry were identified. Indirect standardization was employed to compute standardized incidence ratios (SIRs). Results Counties with SIRs greater than 1 were concentrated around the agricultural region of Slavonia and the coastal region of Dalmatia. However, only Brod-Posavina County and Vukovar-Srijem County had a statistically significant risk of UUC development, where there were 390 and 210% more UUC cases observed than expected, respectively. Only unique to Brod-Posavina County, females were at higher risk (SIR 4.96; 95% CI 3.59–6.34) of developing UUCs than males (SIR 3.03; 95% CI 2.04–4.01) when compared to their Croatian counterparts. Although Brod-Posavina County only made up 3.7% of the total Croatian population (as of 2011), it had the highest frequency of incident UUC cases after the capital City of Zagreb. No elevated cancer risks were noted in the City of Zagreb, even after stratifying by sex. Conclusion Our findings suggest that Brod-Posavina County had the highest cancer risk for UUCs, especially among females, when compared to Croatia as a whole during 2001–2011. Given that a majority of BEN patients develop associated UUCs, concurrent screening programs for UUCs and BEN should be considered not only in endemic areas of BEN but also the surrounding rural areas and amongst at-risk groups such as those undergoing hemodialysis, who frequently develop UUCs, to help clarify BEN-UUC associations by identifying common risk factors while standardizing disease estimates across endemic regions for BEN.

The incidence and prevalence of upper tract urothelial carcinoma: a systematic review

“…Five studies reported on incidence of UTUC according to specific geographical regions [ 14 , 24 , 31 , 34 , 37 ]. The study by Mathew et al [ 37 ] covered 10 regions for both males and females, and a further five regions for males.…”

“…Visser et al [ 14 ] further reported incidence in different regions of Europe between 1995 and 2002 and found northern Europe to have the highest ASR of 12.8 (SE 0.3) per million persons. The high incidence of UTUC in regions with a high prevalence of Balkan endemic nephropathy (BEN) was studied by Medunjanin and colleagues [ 31 ], who reported a high incidence in Croatia geographically associated with a high prevalence of BEN, specifically in the Brod-Posavina county.…”

“…The calculation of age-standardised rates (ASRs) varied according to what population was used in standardisation. In the 13 studies that reported on incidence of UTUC according to sex [14,[19][20][21][22][23][24][29][30][31][32][33][34], the ASR values were adjusted based on different populations, including a European population [14], a standard world population [21], the World Health Organisation (WHO) standard population [32], the 1995 South Korean population [22], and population data from the Australian Bureau of Statistics [34].…”

Histopathological review of renal pelvic tumours of Balkan nephropathy cases from Southern Serbia

“…It appears that, if the tumourigenic agent had generally been in vascular circulation, and then in kidney glomerular filtrate, it only targeted pelvis epithelium without affecting epithelia of the various nephron segments. A recent study of urothelial carcinomas across Croatia [18] cites historic incidence of upper urothelial tract tumours of the ureter and renal pelvis as 5-10 % of all cases, with notably higher incidence in the Slavonski Brod area where the Balkan nephropathy has been endemic for many years. Half of the upper urothelial cancers (n = 608) were in the renal pelvis, both nationally and specifically in the urban area of Zagreb (n = 107) and the rural area around Slavonski Brod (n = 86).…”

Razvoj panurotelijalnog karcinoma nakon transplantacije bubrega u pacijenta s endemskom nefropatijom

“…Specifičnost EN-a je značajno povećan rizik za razvoj UTUC-a 7,11 . Istraživanja u Republici Hrvatskoj pokazala su kako je i do 55 puta veći specifični mortalitet od navedenog karcinoma u endemskim područjima nego u ostalim dijelovima Hrvatske 12,13 . Zbog toga sve pacijente s EN-om treba redovito kontrolirati kako bi se UTUC otkrio u što Karcinomi prijelaznog epitela gornjeg dijela mokraćnog sustava izrazito su rijetki zloćudni tumori.…”