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Advances in Urology
Volume 2008 (2008), Article ID 782381, 7 pages
Review Article

Epidemiology of Kidney Cancer

1Department of Urology, San Pedro Hospital, 26006 Logroño, Spain
2Department of Urology, Miguel Servet University Hospital, 50009 Zaragoza, Spain

Received 24 March 2008; Revised 20 August 2008; Accepted 26 September 2008

Academic Editor: J. Rubio

Copyright © 2008 D. Pascual and A. Borque. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Some tumors are known to have a definite cause-effect etiology, but renal cell carcinoma (RCC) is not one of them precisely. With regard to RCC we can only try to identify some clinical and occupational factors as well as substances related to tumorigenesis. Smoking, chemical carcinogens like asbestos or organic solvents are some of these factors that increase the risk of the RCC. Viral infections and radiation therapy have also been described as risk factors. Some drugs can increase the incidence of RCC as well as other neoplasms. Of course, genetics plays an outstanding role in the development of some cases of kidney cancer. Chronic renal failure, hypertension, and dialysis need to be considered as special situations. Diet, obesity, lifestyle, and habits can also increase the risk of RCC. The aim of this review is to summarize the well-defined causes of renal cell carcinoma.

1. Introduction

Speaking about cancer, one of the most difficult issues is to find a definite and direct cause. There are few tumors with a well-known etiology, but renal cell carcinoma (RCC) is not one of them precisely.

In these cases, we can only try to identify some clinical and occupational factors, or some substances related to carcinogenesis.

Epidemiology is an important tool to answer many questions about cancer origin. Differences in age, gender, and geographic distribution have been reported, and multiple clinical factors related to the development of RCC have been established. Some of them have been thoroughly demonstrated in experimental models and in vitro studies, however not all of them recognized as definite etiologic factors.

2. Material and Methods

A systematic review search strategy was developed to identify publications related to epidemiology of renal cell carcinoma. This search strategy was run in PubMed through the medical subject heading “carcinoma, renal cell” and the subheading of this descriptor “epidemiology.” We limited our search strategy to articles published in the previous 5 years, language English or Spanish, and related to humans.

585 articles were found. Abstracts were evaluated and the full text of articles selected was reviewed. Secondary search from the bibliography of selected articles was also considered.

The European cancer registry-based study on survival and care of cancer patients (EUROCARE) and our experience was considered. Last review was on 31 of March 2008.

3. Demographic Aspects of Renal Cell Carcinoma

Among urologic tumors, RCC takes the third place in incidence, following prostate carcinoma and transitional cell carcinoma of bladder.

Representing two percent of the adult malignancies [1], this malignancy takes the tenth and fourteenth place among men and women, respectively, with a man to woman ratio of 3/2 [2]; see Table 1.

Table 1: Epidemiologic features of the RCC.

The peak incidence occurs in the sixth decade, with 80% of the cases within the 40 to 69-year-old population.

Although the most frequent renal tumor in the childhood is the Wilms tumor, it is important to state that the RCC represents between 2% to 6% of the renal tumors in children, without differences between sexes [3, 4]. Besides, the incidence of both malignancies is similar in the second decade of life. In these early ages the papillary differentiation seems to be more frequent with higher tendency to present a locally advanced and high-degree disease at the moment of the diagnosis [5], However, when comparing stage by stage with adult tumors, we find a better response to surgical treatment and higher survival rates, even with positive nodal disease.

RCC represents 85 to 90% of renal parenchymal malignancies [6, 7].

Among urologic tumors, it is the worst in cancer specific mortality, since more than 40% of the patients with RCC die of the disease, opposite to the 20% mortality observed in prostate cancer or bladder carcinoma.

In United States 30 000 new cases are diagnosed every year, and approximately 12 000 patients die of this disease, with an incidence of near nine cases per 100 000 inhabitants per year. Afroamericans have 10 to 20% higher incidence, and the reason is not completely understood [9].

Most of the cases of RCC are sporadic and only 4% are familiar. The estimated number of new cases in the European Union during 2006 was 63300, with 26400 deaths of RCC [10]. The estimated survival in 5 years rises to 54% in males and 57% in women [11].

Table 2 shows different incidences of RCC in the world.

Table 2: Geographic distribution of RCC [8].

Since 1930 incidence of RCC has been increasing, mostly between 1930 and 1980. Within this period the incidence also rose from 0.7 to 4.2 per 100 000 per year in women and from 1.6 to 9.6 in men [12]. Since 1980 a sharp increase has not been observed comparing to other genitourinary tumors or other type of malignancies. Similarly, deaths caused by RCC had been stable.

Variations of incidence within the first period could be explained by an easier diagnosis, as a result of diffusion and routine use of diagnostic tools such as ultrasound or CT scan, and not due to a real increased incidence of RCC.

It is also important to state that RCC is found incidentally in 1.5% of the autopsies [13].

RCC is more frequent in urban populations rather than in rural ones. This observation may be explained by the sanitary conditions and the smoking habit in urban populations. However it has not been related neither to socioeconomic nor to educational status [14].

There are multiple factors related to the development of RCC; see Table 3. Some of them have been demonstrated in experimental models and in vitro studies, however not all of them can be considered as definite etiologic factors.

Table 3: Some etiologic factors of RCC [15].

Herein, we describe these main factors.

3.1. Smoking

Multiple carcinogenic substances have been identified in tobacco and related to a variety of neoplasms at different levels. A high incidence of RCC in smokers has been shown [16], estimated in 2.3 fold risk ratio, directly related with the number of cigarettes and inversely with age of beginning of the habit. Likewise it has been shown that the carcinogen dimetilnitrosamine induces this neoplasm in experimental studies. Some authors reported that smokers' risk for RCC compares to nonsmokers’ after the fifth year of nonsmoking, but a meta-analysis made by Hunt showed that only after ten years the risk can be similar in both groups [17], depending on the dose of tobacco inhaled. Another study by McLaughin [18] and Lipworth [19] confirmed tobacco as the most important risk factor for renal cancer, detected in 20% of the cases of RCC.

But smoking is not only important in the genesis of RCC, and prognostic nomograms have also been developed [20]. A multivariate study carried out in “Miguel Servet” University Hospital of Zaragoza, Spain (in press), smoking habit increases 2.84 fold (1.27–6,32) the risk of progression of the disease after surgery [21], similarly to previous studies in other countries.

3.2. Chemical Carcinogens

Some radiological contrasts have been associated with an increased incidence of RCC [22]. Although Cycasin (a substance derived from a palm fruit that grows in the island of Guam) induces RCC in animals, a higher incidence of this neoplasm within the island population could not be shown.

Cadmium was demonstrated to have influence on the development of RCC in smokers [23, 24].

(i)Asbestos. A significantly elevated mortality rate for kidney cancer has been reported in two cohort studies, on insulation workers [25] and on asbestos products workers [26]. Autopsy surveys and animal studies indicate that asbestos fibers can be deposited in kidney tissue.(ii)Organic solvents. Pesticides, copper sulphate, benzidine, benzene herbicides, and vinyl chloride have been found as risk factors of RCC in prolonged exposure. A dose dependent effect has been seen only for organic solvents and copper sulphate [27, 28]. Recent reviews of cohort studies found little or no evidence of an increased risk for RCC among people exposed to gasoline and petroleum derived products [29, 30].(iii)Polycyclic aromatic hydrocarbons. Workers exposed to high levels of polycyclic aromatic hydrocarbons like coke and coal oven workers, firefighters, asphalt, and tar have been reported to be at increased risk for kidney cancer.

3.3. Radiation

Ionizing radiation appears to increase the RCC risk slightly, especially among patients treated for ankylosing spondylitis and cervical cancer [31]. An increased risk has also been reported for patients receiving radium 224 for bone tuberculosis and ankylosing spondylitis [32].

3.4. Viruses

The immunosuppressant state related to the HIV infection determines that prevalence of RCC in the infected population rises 8.5 times compared to the prevalence of the noninfected ones.

The influence of the polyomavirus SV 40 and of the adenovirus 7 has also been detected in experimental studies.

A clear-cut association was found between herpes-type virus and renal tumors in toads. These findings led to search for evidence of herpes virus proteins in human tumors as well. Although herpes simplex proteins were found in only one study [33, 34], these findings need to be confirmed by further research.

3.5. Diuretics

This type of drugs which inhibits water reabsorption on the renal tubule cells seemed to be responsible for a higher incidence of RCC in patients with chronic intake of diuretics [35, 36]. Even though, it is noteworthy that hydrochlorothiazide and furosemide (both effective at the renal tubule level) induce tubular cell adenomas and adenocarcinomas of the kidney in rats [37]. But Yuan [38] showed in his study that an adequate use of diuretics for treating hypertension eliminates the risk associated with the above mentioned drugs, differentiating the influence of hypertension as a risk factor for RCC rather than diuretics.

3.6. Analgesics

This is a controverted topic. Several studies reported an increased incidence of RCC in patients with chronic intake of analgesics like paracetamol, salicylates, or phenacetin [39, 40], however in other studies this relationship has not been confirmed neither for time of consumption nor for dose of the drug taken [41].

Although a heavy use of drugs containing phenacetin has been clearly demonstrated to increase the risk for transitional cancer of the renal pelvis, the association with RCC is much weaker. On the other hand, an increased risk of RCC associated with aspirin or acetaminophen consumers was observed [42], but others believe that neither acetaminophen nor other analgesics have been convincingly linked with RCC [19].

3.7. Oestrogens (dietilestilbestrol)

Although oestrogens can induce RCC in the animal model, little evidence supports an association of the disease with oestrogens in humans [43] and only weak relation has been reported for the use of oestrogens after menopause and for oral contraceptives [44].

3.8. Inheritance

Most of the cases of RCC are sporadic; however there are some defined types of RCC with a hereditary pattern [45].

(1) Von Hippel-Lindau (VHL) Disease
The VHL disease is inherited through an autosomal dominant trait. The syndrome is caused by germline mutations of the VHL tumor suppressor gene, located on chromosome 3p25-26; these mutations can virtually always be identified [46]. The VHL protein takes part in cell cycle regulation and angiogenesis [47]. Patients develop capillary haemangioblastomas of the central nervous system and retina, clear cell carcinoma, phaeochromocytoma, pancreatic, and inner ear tumors.
The clinical diagnostic criteria of VHL disease consist of
(i)presence of capillary haemangioblastoma in the central nervous system or retina,(ii)presence of one of the typical VHL associated extraneural tumors, within pertinent family history.
Fourty to sixty percent of the patients with VHL disease present an RCC. Although they are usually low-grade tumors, the progress rate to metastasis is around 30% [48].
Renal lesions in carriers of VHL germline mutations are either cysts or clear cell RCC. They are typically multifocal and bilateral.

(2) Hereditary Papillary Renal Carcinoma
This type of renal carcinoma is an inherited tumor syndrome with autosomal dominant trait and of late onset, with multiple and bilateral papillary renal cell carcinomas type 1. The disease is caused by activating mutations of the MET oncogene which maps the chromosome 7q31.

(3) Hereditary Leiomyomatosis and Renal Cell Carcinoma
This is an autosomal dominant tumor syndrome with germline mutations in the FH gene (chromosome lq42.3–q43), These patients have the tendency to acquire benign leiomyomas of the skin and the uterus, and occasionally papillary renal cell carcinoma type 2 and uterine leiomyosarcomas.

(4) Birt-Hogg-Dube Syndrome
This syndrome is characterized by benign skin tumors, specifically fibrofolliculomas, trichodiscomas, and acrochordons. Multiple renal tumors and spontaneous pneumothoraces are also frequent. We can find chromophobe RCC, typical RCC, hybrid oncocytoma, papillary RCC, or oncocytic tumors.
The Birt-Hogg-Dube gene maps the chromosome 17p11.2 and encodes the protein called folliculin. This gene is also involved in sporadic RCC [49].

(5) Familiar Clear Cell Renal Cell Carcinoma
These families present a hereditary form of multiple, bilateral clear cell RCC but without any clinical evidence of suffering the von Hippel-Lindau disease.
This hereditary cancer is characterized to present translocations affecting the chromosome 3. Translocations have been described among the chromosome 3 and the chromosomes 8 [50], 6 [51, 52], 2 [53, 54], 1 [55], and 4 [48].

3.9. Acquired Cystic Disease/Chronic Dialysis

Approximately the 35 to 47% of the patients on dialysis and specially those with a very long history present acquired cystic disease. Some patients with this disease develop a papillary hyperplasia in the epithelium of the cysts that would be the origin of the RCC [56, 57].

Approximately the 5 to 9% of the patients with acquired cystic disease will develop an RCC [58], showing a higher incidence than the general population. As such, we suggest a close follow-up in the kidney-transplant population, and therefore the immune-suppressed individuals who are on dialysis for a long time, due to a high risk of developing RCC.

2.10. Diet and Obesity

Hypercaloric diet and obesity seem to be associated with a higher risk for suffering of RCC. Obesity accounts for about 30% of renal cancers [19].

Some studies relate a higher incidence of RCC with high body mass index. The relative risk was found to be 3.3 in males and 2.3 in females [59].

The mechanism of obesity to cause kidney cancer is not clear. Hormonal changes such as increased levels of endogenous oestrogens in the obese may be the mechanism through which oestrogens induce renal cancer as observed in animal models. However, there is scant epidemiologic evidence supporting hormonal carcinogenesis regarding RCC. Obesity may also predispose to arterionephrosclerosis, which may render the renal tubules more susceptible to carcinogens. Elevated cholesterol levels associated with obesity might also play a role, as suggested by animal studies showing that cholesterol-lowering drugs provide some protection against RCC. Cholesterol and other lipids may favour tumor development by an inhibitory effect on immune cells.

Low vitamin D level, which is usually present in obese patients, may predispose to acquire RCC. This vitamin is known to have inhibitory effects on the growth of RCC cell lines in vitro [60].

Finally, Lipworth [19] reported that the only consistent protective factor is consumption of fruit and vegetables.

2.11. Coffee, Alcohol, and Other Beverages

Case-control studies have not confirmed the suggested relationship between kidney cancer and consumption of coffee, when adjusting the smoking variable. Although two studies have suggested a positive association, a two-fold increased risk in both sexes was associated with the use of decaffeinated coffee. In another study, an increased risk of RCC was found only among women with regular coffee intake [61]. No dose-dependent risk was reported in either study.

On the other hand, a significant lower risk was reported in Norway among consumers of seven or more cups of coffee compared to those who drink two or fewer cups daily, representing a relative risk of 0.25 [62]. Review studies indicate that coffee consumption does not increase RCC risk.

Few studies have shown an increased risk of RCC among tea women consumers [63]. Another study has found a dose-response relationship between tea consumption and kidney cancer mortality [64]. The etiologic significance of these findings in direct relationship with tea tannins is not clear [65].

The association between alcoholism and kidney cancer mortality has not been demonstrated by well-deisgned studies [66]. In fact, a recent case-control study found a statistically significant inverse association between alcohol consumption and RCC risk [67]. No increase in mortality from kidney cancer has been reported either within alcoholic patients or brewery workers [68].

2.12. Physical Activity

A moderate recreational activity reduces the risk of renal cancer both in men and women. The mechanism is not clear, but there is no doubt that energy expenditure is one of the major determinants for obesity, which is a strong risk factor for RCC.

2.13. Hypertension

Hypertension seems to be significant for the development of kidney cancer. The strength of this relationship is reduced with the use of diuretics and other antihypertensive drugs, regardless of some of these drugs have been associated with RCC risk. The main problem consists to identify whether the increased risk is due to hypertension or antihypertensive medications.

Despite the mechanism for hypertension to cause renal cancer is not completely understood [69] it seems that metabolic and/or functional changes in the renal tubular cells produce carcinogenesis. Wide case-control studies have only found a slight relation between RCC and hypertension [70]. Further studies are needed.

2.14. Alterations in Development of the Kidney

The anomalous development of the kidneys may act as a teratogenic factor.

In horseshoe kidneys, the area of the isthmus is prone to develop tumors [71], due to an anomalous migration of the cells toward this area. However, although the most frequent tumor developed in this malformation is the RCC, the incidence remains identical to that of the general population, without differences in evolution or prognosis [72].

In conclusion we can affirm that respect RCC, like in other malignant diseases, ethiology, and risk factors are not completely understood. There is some evidence that certain situations, drugs, habits, or genetics are related to the development of renal cancer, but several studies found controversial results and different degrees of evidence.

Smoking and obesity seem to be the most important independent risk factors in the genesis of RCC, reported by different authors.

Chromosomal mutations were clearly identified in the context of well-defined hereditary diseases.

The adequate use of diuretics and analgesics may be recognized as protective factors not only for RCC but for other diseases as well.

General healthy habits like limiting alcohol and coffee intake, decreasing the number of cigarettes, lowering fat consumption, keeping a suitable weight, and practicing regular exercise may reduce the risk and indicence of RCC.


  1. F. Algaba, A. Moreno, and I. Trias, “Tumores de pene,” in Uropatología Tumoral. Capitulo II, Tumores Renales, pp. 21–101, Pulso Ediciones, Barcelona, Spain, 1996. View at Google Scholar
  2. J. K. McLaughlin and L. Lipworth, “Epidemiologic aspects of renal cell cancer,” Seminars in Oncology, vol. 27, no. 2, pp. 115–123, 2000. View at Google Scholar
  3. A. L. Freedman, T. S. Vates, T. Stewart, N. Padiyar, A. D. Perlmutter, and C. A. Smith, “Renal cell carcinoma in children: the detroit experience,” The Journal of Urology, vol. 155, no. 5, pp. 1708–1710, 1996. View at Publisher · View at Google Scholar
  4. H. Asanuma, H. Nakai, M. Takeda et al., “Renal cell carcinoma in children: experience at a single institution in Japan,” The Journal of Urology, vol. 162, no. 4, pp. 1402–1405, 1999. View at Publisher · View at Google Scholar
  5. A. A. Renshaw, H. Zhang, C. L. Corless, J. A. Fletcher, and M. R. Pins, “Solid variants of papillary (chromophil) renal cell carcinoma: clinicopathologic and genetic features,” The American Journal of Surgical Pathology, vol. 21, no. 10, pp. 1203–1209, 1997. View at Publisher · View at Google Scholar
  6. J. E. Robles, D. Rosell, J. J. Zudaire, and J. M. Berián, “Epidemiología de los tumores del parénquima renal,” Revista de medicina de la Universidad de Navarra, vol. 43, no. 2, pp. 68–76, 1999. View at Google Scholar
  7. A. Jemal, R. Siegel, E. Ward et al., “Cancer statistics, 2006,” Ca: A Cancer Journal for Clinicians, vol. 56, no. 2, pp. 106–130, 2006. View at Google Scholar
  8. S. L. Parker, T. Tong, S. Bolden, and P. A. Wingo, “Cancer statistics, 1997,” Ca: A Cancer Journal for Clinicians, vol. 47, no. 1, pp. 5–27, 1997. View at Publisher · View at Google Scholar
  9. W.-H. Chow, S. S. Devesa, J. L. Warren, and J. F. Fraumeni Jr., “Rising incidence of renal cell cancer in the United States,” Journal of the American Medical Association, vol. 281, no. 17, pp. 1628–1631, 1999. View at Publisher · View at Google Scholar
  10. J. Ferlay, P. Autier, M. Boniol, M. Heanue, M. Colombet, and P. Boyle, “Estimates of the cancer incidence and mortality in Europe in 2006,” Annals of Oncology, vol. 18, no. 3, pp. 581–592, 2007. View at Publisher · View at Google Scholar
  11. EUROCARE-3, March 2008,
  12. D. L. Katz, T. Zheng, T. R. Holford, and J. Flannery, “Time trends in the incidence of renal carcinoma: analysis of Connecticut tumor Registry data, 1935–1989,” International Journal of Cancer, vol. 58, no. 1, pp. 57–63, 1994. View at Publisher · View at Google Scholar
  13. S. Hellsten, T. Berge, and L. Wehlin, “Unrecognized renal cell carcinoma. Clinical and diagnostic aspects,” Scandinavian Journal of Urology and Nephrology, vol. 15, no. 3, pp. 269–272, 1981. View at Google Scholar
  14. J. K. McLaughlin, W. J. Blot, and S. S. Devesa, “Renal cancer,” in Cancer Epidemiology and Prevention, D. Schoffendeld and J. F. Fraumeni Jr., Eds., pp. 1142–1155, Oxford University Press, New York, NY, USA, 2nd edition, 1996. View at Google Scholar
  15. J. K. McLaughlin, P. Lindblad, A. Mellemgaard et al., “International renal-cell cancer study. I. Tobacco use,” International Journal of Cancer, vol. 60, no. 2, pp. 194–198, 1995. View at Publisher · View at Google Scholar
  16. N. J. Vogelzang and W. M. Stadler, “Kidney cancer,” The Lancet, vol. 352, no. 9141, pp. 1691–1696, 1998. View at Publisher · View at Google Scholar
  17. J. D. Hunt, O. L. van der Hel, G. P. McMillan, P. Boffetta, and P. Brennan, “Renal cell carcinoma in relation to cigarette smoking: meta-analysis of 24 studies,” International Journal of Cancer, vol. 114, no. 1, pp. 101–108, 2005. View at Publisher · View at Google Scholar
  18. J. K. McLaughlin and L. Lipworth, “Epidemiologic aspects of renal cell cancer,” Seminars in Oncology, vol. 27, no. 2, pp. 115–123, 2000. View at Google Scholar
  19. L. Lipworth, R. E. Tarone, and J. K. McLaughlin, “The epidemiology of renal cell carcinoma,” The Journal of Urology, vol. 176, no. 6, part 1, pp. 2353–2358, 2006. View at Publisher · View at Google Scholar
  20. B. R. Lane, D. Babineau, M. W. Kattan et al., “A preoperative prognostic nomogram for solid enhancing renal tumors 7?cm or less amenable to partial nephrectomy,” The Journal of Urology, vol. 178, no. 2, pp. 429–434, 2007. View at Publisher · View at Google Scholar
  21. D. Pascual, Carcinoma de células renales. Modelo predictivo de progresión, Tesis, University of Zaragoza, Zaragoza, Spain, 2008.
  22. G. A. Bannayan and D. L. Lamm, “Renal cell tumors,” Pathology Annual, vol. 15, part 2, pp. 271–308, 1980. View at Google Scholar
  23. L. N. Kolonel, “Association of cadmium with renal cancer,” Cancer, vol. 37, no. 4, pp. 1782–1787, 1976. View at Publisher · View at Google Scholar
  24. S. A. Baynham, H. P. Katner, and K. B. Cleveland, “Increased prevalence of renal cell carcinoma in patients with HIV infection,” AIDS Patient Care STDS, vol. 11, no. 3, pp. 161–165, 1997. View at Google Scholar
  25. I. J. Selikoff, E. C. Hammond, and H. Seidman, “Mortality experience of insulation workers in the United States and Canada, 1943–1976,” Annals of the New York Academy of Sciences, vol. 330, pp. 91–116, 1979. View at Publisher · View at Google Scholar
  26. P. E. Enterline, J. Hartley, and V. Henderson, “Asbestos and cancer: a cohort followed up to death,” British Journal of Industrial Medicine, vol. 44, no. 6, pp. 396–401, 1987. View at Google Scholar
  27. L. Buzio, M. Tondel, G. De Palma et al., “Occupational risk factors for renal cell cancer. An Italian case-control study,” Medicina del Lavoro, vol. 93, no. 4, pp. 303–309, 2002. View at Google Scholar
  28. J. Hu, Y. Mao, and K. White, “Renal cell carcinoma and occupational exposure to chemicals in Canada,” Occupational Medicine, vol. 52, no. 3, pp. 157–164, 2002. View at Publisher · View at Google Scholar
  29. C. K. Redmond, A. Ciocco, J. W. Lloyd, and H. W. Rush, “Long-term mortality study of steelworkers. VI. Mortality from malignant neoplasms among coke oven workers,” Journal of Occupational Medicine, vol. 14, no. 8, pp. 621–629, 1972. View at Google Scholar
  30. A. Mellemgaard, G. Engholm, J. K. McLaughlin, and J. H. Olsen, “Occupational risk factors for renal-cell carcinoma in Denmark,” Scandinavian Journal of Work, Environment and Health, vol. 20, no. 3, pp. 160–165, 1994. View at Google Scholar
  31. J. D. Boice Jr., G. Engholm, R. A. Kleinerman et al., “Radiation dose and second cancer risk in patients treated for cancer of the cervix,” Radiation Research, vol. 116, no. 1, pp. 3–55, 1988. View at Publisher · View at Google Scholar
  32. H. Spiess, C. W. Mays, and B. Chmelvesky, “Radium 244 in humans,” in Risks from Radium and Thorotrast, D. M. Taylor, C. W. Mays, and G. B. Gerber, Eds., BIR Report 21, pp. 7–12, British Institute of Radiology, London, UK, 1989. View at Google Scholar
  33. M. Murai and M. Oya, “Renal cell carcinoma: etiology, incidence and epidemiology,” Current Opinion in Urology, vol. 14, no. 4, pp. 229–233, 2004. View at Publisher · View at Google Scholar
  34. A. S. Parker, J. R. Cerhan, C. F. Lynch, B. C. Leibovich, and K. P. Cantor, “History of urinary tract Infection and risk of renal cell carcinoma,” American Journal of Epidemiology, vol. 159, no. 1, pp. 42–48, 2004. View at Publisher · View at Google Scholar
  35. A. Mellemgaard, H. Moller, and J. H. Olsen, “Diuretics may increase risk of renal cell carcinoma,” Cancer Causes and Control, vol. 3, no. 4, pp. 309–312, 1992. View at Publisher · View at Google Scholar
  36. W. D. Finkle, J. K. McLaughlin, S. A. Rasgon, H. H. Yeoh, and J. E. Low, “Increased risk of renal cell cancer among women using diuretics in the United States,” Cancer Causes and Control, vol. 4, no. 6, pp. 555–558, 1993. View at Publisher · View at Google Scholar
  37. W. Lijinsky and M. D. Reuber, “Pathologic effects of chronic administration of hydrochlorothiazide, with and without sodium nitrite, to F344 rats,” Toxicology and Industrial Health, vol. 3, no. 3, pp. 413–422, 1987. View at Google Scholar
  38. J.-M. Yuan, J. E. Castelao, M. Gago-Domínguez, R. K. Ross, and M. C. Yu, “Hypertension, obesity and their medications in relation to renal cell carcinoma,” British Journal of Cancer, vol. 77, no. 9, pp. 1508–1513, 1998. View at Google Scholar
  39. N. Kreiger, L. D. Marrett, L. Dodds, S. Hilditch, and G. A. Darlington, “Risk factors for renal cell carcinoma: results of a population-based case-control study,” Cancer Causes and Control, vol. 4, no. 2, pp. 101–110, 1993. View at Publisher · View at Google Scholar
  40. P. Lindblad, J. K. McLaughlin, A. Mellemgaard, and H.-O. Adami, “Risk of kidney cancer among patients using analgesics and diuretics: a population-based cohort study,” International Journal of Cancer, vol. 55, no. 1, pp. 5–9, 1993. View at Publisher · View at Google Scholar
  41. M. McCredie, W. Pommer, J. K. McLaughlin et al., “International renal-cell cancer study. II. Analgesics,” International Journal of Cancer, vol. 60, no. 3, pp. 345–349, 1995. View at Publisher · View at Google Scholar
  42. A. Mellemgaard, S. Niwa, E. S. Mehl, G. Engholm, J. K. McLauglin, and J. H. Olsen, “Risk factors for renal cell carcinoma in Denmark: role of medication and medical history,” International Journal of Epidemiology, vol. 23, no. 5, pp. 923–930, 1994. View at Publisher · View at Google Scholar
  43. J. K. McLaughlin and L. M. Schuman, “Epidemiology of renal cell carcinoma,” in Reviews in Cancer Epidemiology, A. M. Lilienfeld, Ed., vol. 2, pp. 170–210, Elsevier/North Holland, New York, NY, USA, 1983. View at Google Scholar
  44. N. R. Asal, J. R. Geyer, D. R. Risser, E. T. Lee, S. Kadamani, and N. Cherng, “Risk factors in renal cell carcinoma. II. Medical history, occupation, multivariate analysis, and conclusions,” Cancer Detection and Prevention, vol. 13, no. 3-4, pp. 263–279, 1988. View at Google Scholar
  45. M. J. Merino, D. M. Eccles, W. M. Linehan et al., “Familial renal cell carcinoma,” in Pathology & Genetics. Tumours of the Urinary System and Male Genital Organs, I. N. Eble, G. Sauter, J. I. Epstein, and I. A. Sesterhenn, Eds., pp. 15–22, IARC Press, Lyon, France, 2004. View at Google Scholar
  46. C. Stolle, G. Glenn, B. Zbar et al., “Improved detection of germline mutations in the von Hippel-Lindau disease tumor suppressor gene,” Human Mutation, vol. 12, no. 6, pp. 417–423, 1998. View at Publisher · View at Google Scholar
  47. P. H. Maxwell, M. S. Wiesener, G.-W. Chang et al., “The tumour suppressor protein VHL targets hypoxia-inducible factors for oxygen-dependent proteolysis,” Nature, vol. 399, no. 6733, pp. 271–275, 1999. View at Publisher · View at Google Scholar
  48. J. L. Ruiz Cerda and J. F. Jiménez, “Diagnostico y tratamiento quirúrgico de la recidiva y enfermedad metastásica del adenocarcinoma renal,” in Diagnostico y Tratamiento de la Recidiva en los Tumores Urológico, pp. 1–22, Ed Grupo Aula Medica, Madrid, Spain, 1996. View at Google Scholar
  49. S. K. Khoo, K. Kahnoski, J. Sugimura et al., “Inactivation of BHD in sporadic renal tumors,” Cancer Research, vol. 63, no. 15, pp. 4583–4587, 2003. View at Google Scholar
  50. A. J. Cohen, F. P. Li, S. Berg et al., “Hereditary renal-cell carcinoma associated with a chromosomal translocation,” The New England Journal of Medicine, vol. 301, no. 11, pp. 592–595, 1979. View at Google Scholar
  51. G. Kovacs, P. Brusa, and W. De Riese, “Tissue-specific expression of a constitutional 3;6 translocation: development of multiple bilateral renal-cell carcinomas,” International Journal of Cancer, vol. 43, no. 3, pp. 422–427, 1989. View at Publisher · View at Google Scholar
  52. A. Geurts van Kessel, R. F. Suijkerbuijk, R. J. Sinke, L. Looijenga, J. W. Oosterhuis, and B. de Jong, “Molecular cytogenetics of human germ cell tumours: i(12p) and related chromosomal anomalies,” European Urology, vol. 23, no. 1, pp. 23–29, 1993. View at Google Scholar
  53. M. I. Koolen, A. P. M. van der Meyden, D. Bodmer et al., “A familial case of renal cell carcinoma and a t(2;3) chromosome translocation,” Kidney International, vol. 53, no. 2, pp. 273–275, 1998. View at Publisher · View at Google Scholar
  54. J. Podolski, T. Byrski, S. Zajaczek et al., “Characterization of a familial RCC-associated t(2;3)(q33;q21) chromosome translocation,” Journal of Human Genetics, vol. 46, no. 12, pp. 685–693, 2001. View at Publisher · View at Google Scholar
  55. H.-O. Kanayama, W.-O. Lui, M. Takahashi et al., “Association of a novel constitutional translocation t(1q;3q)with familial renal cell carcinoma,” Journal of Medical Genetics, vol. 38, no. 3, pp. 165–170, 2001. View at Publisher · View at Google Scholar
  56. J. F. Brennan, M. M. Stilmant, R. K. Babayan, and M. B. Siroky, “Acquired renal cystic disease: implications for the urologist,” British Journal of Urology, vol. 67, no. 4, pp. 342–348, 1991. View at Google Scholar
  57. P. S. Chandhoke, R. J. Torrence, R. V. Clayman, and M. Rothstein, “Acquired cystic disease of the kidney: a management dilemma,” The Journal of Urology, vol. 147, no. 4, pp. 969–974, 1992. View at Google Scholar
  58. M. A. Matson and E. P. Cohen, “Acquired cystic kidney disease: occurrence, prevalence, and renal cancers,” Medicine, vol. 69, no. 4, pp. 217–226, 1990. View at Google Scholar
  59. J. A. Shapiro, M. A. Williams, and N. S. Weiss, “Body mass index and risk of renal cell carcinoma,” Epidemiology, vol. 10, no. 2, pp. 188–191, 1999. View at Publisher · View at Google Scholar
  60. C. L. Amling, “The association between obesity and the progression of prostate and renal cell carcinoma,” Urologic Oncology: Seminars and Original Investigations, vol. 22, no. 6, pp. 478–484, 2004. View at Publisher · View at Google Scholar
  61. R. J. Menezes, G. Tomlinson, and N. Kreiger, “Physical activity and risk of renal cell carcinoma,” International Journal of Cancer, vol. 107, no. 4, pp. 642–646, 2003. View at Publisher · View at Google Scholar
  62. B. K. Jacobsen, E. Bjelke, G. Kvale, and I. Heuch, “Coffee drinking, mortality, and cancer incidence: results from a Norwegian prospective study,” Journal of the National Cancer Institute, vol. 76, no. 5, pp. 823–831, 1986. View at Google Scholar
  63. N. R. Asal, D. R. Risser, S. Kadamani, J. R. Geyer, E. T. Lee, and N. Cherng, “Risk factors in renal cell carcinoma: I. Methodology, demographics, tobacco, beverage use, and obesity,” Cancer Detection and Prevention, vol. 11, no. 3–6, pp. 359–377, 1988. View at Google Scholar
  64. L. J. Kinlen, A. N. Willows, P. Goldblatt, and J. Yudkin, “Tea consumption and cancer,” British Journal of Cancer, vol. 58, no. 3, pp. 397–401, 1988. View at Google Scholar
  65. International Agency for Research on Cancer, “Tannic acid and tannins,” IARC Monographs on the Evaluation of Carcinogenic Risks to Humans, vol. 10, pp. 253–262, 1976. View at Google Scholar
  66. R. C. Brownson, “A case-control study of renal cell carcinoma in relation to occupation, smoking, and alcohol consumption,” Archives of Environmental Health, vol. 43, no. 3, pp. 238–241, 1988. View at Google Scholar
  67. A. Mellemgaard, G. Engholm, J. K. McLaughlin, and J. H. Olsen, “Risk factors for renal cell carcinoma in Denmark. I. Role of socioeconomic status, tobacco use, beverages, and family history,” Cancer Causes and Control, vol. 5, no. 2, pp. 105–113, 1994. View at Publisher · View at Google Scholar
  68. H.-O. Adami, J. K. McLaughlin, A. W. Hsing et al., “Alcoholism and cancer risk: a population-based cohort study,” Cancer Causes and Control, vol. 3, no. 5, pp. 419–425, 1992. View at Publisher · View at Google Scholar
  69. J. A. Shapiro, M. A. Williams, N. S. Weiss, A. Stergachis, A. Z. LaCroix, and W. E. Barlow, “Hypertension, antihypertensive medication use, and risk of renal cell carcinoma,” American Journal of Epidemiology, vol. 149, no. 6, pp. 521–530, 1999. View at Google Scholar
  70. E. Grossman, F. H. Messerli, V. Boyko, and U. Goldbourt, “Is there an association between hypertension and cancer mortality?” American Journal of Medicine, vol. 112, no. 6, pp. 479–486, 2002. View at Publisher · View at Google Scholar
  71. M. Hohenfellner, D. Schultz-Lampel, A. Lampel, F. Steinbach, B. M. Cramer, and J. W. Thüroff, “Tumor in the horseshoe kidney: clinical implications and review of embryogenesis,” The Journal of Urology, vol. 147, no. 4, pp. 1098–1102, 1992. View at Google Scholar
  72. J. Rubio Briones, R. Regalado, and F. Sánchez, “Incidencia de patología tumoral en los riñones en herradura,” European Urology, vol. 6, no. 4, pp. 306–310, 1999. View at Google Scholar