QJM Advance Access published October 1, 2014 Q J Med doi:10.1093/qjmed/hcu195

Advance Access Publication 9 September 2014

The risk of kidney cancer in patients with kidney stones: a systematic review and meta-analysis W. CHEUNGPASITPORN1, C. THONGPRAYOON1, O.A. O’CORRAGAIN2, P.J. EDMONDS3, P. UNGPRASERT4, W. KITTANAMONGKOLCHAI1 and S.B. ERICKSON1 From the 1Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota, USA, 2 University College Cork, Cork, Ireland, 3SUNY Upstate Medical University, Syracuse, NY, USA and 4 Division of Rheumatology, Mayo Clinic, Rochester, Minnesota, USA Address correspondence to Wisit Cheungpasitporn, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA. email: [email protected] Received 2 August 2014 and in revised form 21 August 2014

Summary

Introduction Kidney stones are one of the most common urological problems. The incidence of kidney stones is increasing with an estimated global prevalence of 10–15%.1–4 In the USA, approximately 13% of men and 7% women will develop a kidney stone during their life time.1,4 Similar to the incidence of kidney stones, the incidence of renal cell carcinoma (RCC), the most

patients with kidney stones was 1.76 (95% CI, 1.24–2.49). The subgroup analysis found that the history of kidney stones was associated with increased RCC risk only in males (RR, 1.41 [95% CI, 1.11–1.80]), but not in females (RR, 1.13 [95% CI, 0.86–1.49]). Five studies were selected to assess the association between a history of kidney stones and TCC. The pooled RR of TCC in patients with kidney stones was 2.14 (95% CI, 1.35–3.40). Conclusion: Our study demonstrates a significant increased risk of RCC and TCC in patients with prior kidney stones. However, the increased risk of RCC was noted only in male patients. This finding suggests that a history of kidney stones is associated with kidney cancer and may impact clinical management and cancer surveillance.

common type of renal parenchymal tumor, continues to increase with nearly 51 000 cases annually in the USA.5 Although transitional cell carcinoma (TCC) of the upper urinary tract involving the renal pelvis and ureter is rare, representing only 5% of all urothelial tumors,6 the overall incidence of TCC and the rate of in situ neoplasms of upper urinary tract also appears to be increasing over the past 20 years.7

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Background: The objective of this meta-analysis was to evaluate the association between a history of kidney stones and kidney cancer. Methods: A literature search was performed from inception until June 2014. Studies that reported odds ratios or hazard ratios comparing the risk of renal cell carcinoma (RCC) and transitional cell carcinoma (TCC) of the upper urinary tract in patients with the history of kidney stones versus those without the history of kidney stones were included. Pooled risk ratios (RRs) and 95% confidence interval (CI) were calculated using a random-effect, generic inverse variance method. Result: Seven studies were included in our analysis to assess the association between a history of kidney stones and RCC. The pooled RR of RCC in

W. Cheungpasitporn et al. As the incidences of kidney stones, RCC and TCC are all trending upward, it is possible that a history of kidney stones is associated with these two kidney cancers. Kidney stones have also been proposed to cause chronic irritation, subsequently leading to proliferation and the development of malignant neoplasms.8,9 The reported risks of RCC and TCC in patients with a history of kidney stones, however, are still conflicting. Several studies have demonstrated that a history of kidney stones is associated with RCC10–15 and TCC.8,10,12 Conversely, a number of studies have shown that a history of kidney stones is not a risk factor for RCC8 or TCC.10,16 The objective of this meta-analysis was to evaluate the association between a history of kidney stones and two common kidney cancers, RCC and TCC.

Data extraction A standardized data collection form was used to extract the following information: last name of the first author, title of the article, study design, year of study, country of origin, year of publication, sample size, characteristics of included participants, method used to diagnose kidney stones, RCC and TCC, mean duration of follow up and adjusted effect estimates with 95% CI. The two investigators mentioned above independently performed this data extraction.

Statistical analysis

Inclusion criteria

Results

The inclusion criteria were as follows: (i) randomized controlled trials or observational studies (case–control, cross-sectional or cohort studies) published as original studies to evaluate the association between kidney stones and the two most common kidney cancers, RCC and TCC, (ii) odds ratios, relative risks, hazard ratios or standardized incidence ratio with 95% confidence intervals (CIs) were provided and (iii) a reference group composed of participants without a history of kidney stones was utilized. Study eligibility was independently determined by the two investigators noted above. Differing decisions were resolved by mutual consensus. The quality of each study was independently evaluated by each investigator using Newcastle-Ottawa quality assessment scale.17

Our search strategy yielded 7201 potentially relevant articles. 7003 articles were excluded based on title and abstract for clearly not fulfilling inclusion criteria on the basis of the type of article, study design, population or outcome of interest. 198 articles underwent full-length article review. 189 articles were excluded (105 articles were not observational studies and 84 articles did not report the outcomes of interest). Nine articles met our inclusion criteria.8,10–16,21 Seven studies (six case–control studies and one retrospective cohort study) with 62 925 patients with kidney stones were included in the data analysis for the risk of RCC.8,10–15 Five studies (four case–control studies and one retrospective cohort study) with 62 377 patients with kidney stones were included in the data analysis for the risk of

Methods Search strategy

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Two investigators (W.C. and C.T.) independently searched published studies indexed in MEDLINE, EMBASE and the Cochrane database from inception to June 2014 using the terms ‘kidney calculi,’ ‘nephrolithiasis’ and ‘kidney stone’ combined with the terms ‘kidney neoplasms’ and ‘kidney cancer.’ A manual search for additional relevant studies using references from retrieved articles was also performed. Conference abstracts and unpublished studies were excluded. Detailed search strategy is available as online supplementary data.

Review Manager 5.2 software from the Cochrane Collaboration was used for data analysis. Point estimates and standard errors were extracted from individual studies and were combined by the generic inverse variance method of DerSimonian and Laird.18 Given the high likelihood of between study variances, we used a random-effect model rather than a fixed-effect model. Statistical heterogeneity was assessed using the Cochran’s Q test. This statistic is complemented with the I2 statistic, which quantifies the proportion of the total variation across studies that is due to heterogeneity rather than chance. A value of I2 of 0–25% represents insignificant heterogeneity, 26–50% low heterogeneity, 51–75% moderate heterogeneity and more than 75% high heterogeneity.19 The presence of publication bias was assessed by funnel plots of the logarithm of odds ratios versus their standard errors.20 The post hoc analysis was performed to assess the sex-specific association between kidney stones and kidney cancer.

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1984

All white residents of seven-county St. PaulMinneapolis who were diagnosed with RCC between 1974 and 1979. Cases were identified by reviewing medical records of all hospitals. Review of medical records.

Study design

Year of publication

Cases

Controls

Sex and age-matched subjects randomly selected from same area.

Case–control

Country

Diagnosis of RCC/TCC

McLaughlin et al.13 USA.

All residents of the study areas (Sydney, Denmark, Uppsala and MN) who were diagnosed with RCC between 1989 and 1991. Cases were identified from the population-based registry of those areas. Diagnostic code from the registry. Sex and age-matched subjects randomly selected from same area.

All residents of New South Wales who were diagnosed with RCC or TCC between 1989 and 1990. Cases were identified from the NSW cancer registry.

Diagnostic code from the registry. Subjects randomly selected from NSW area.

All residents of Northern Italy who were diagnosed with RCC between 1986 and 1989 in participating hospitals. Cases were identified by reviewing medical records of those hospitals. Review of medical records. Sex and age-matched admitted patients randomly selected from the same hospital.

All residents of Boston Metropolitan area who were diagnosed with RCC between 1976 and 1983 in 37 participating hospitals. Cases were identified by reviewing medical records of those hospitals. Review of medical records. Sex and agematched subjects randomly selected from same area.

All residents of Los Angeles county who were diagnosed with TCC between 1978 and 1982. Cases were identified from the tumor registry of Los Angeles county.

Sex, race and age-matched subjects randomly selected from same area.

Diagnostic code from the registry.

1996

Schlehofer et al.14 Australia, Denmark, Sweden and USA. Case–control

1992

Case–control

McCredie et al.12 Australia

1990

Case–control

Talamini et al.15 Italy

1990

Case–control

Maclure et al.11 USA.

1989

Case–control

USA.

Ross et al.16

Main characteristics of studies included in the meta-analysis

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Table 1

Diagnostic code from the national cancer registry. Using Swedish age- and sex-specific general population incidence rates for RCC/TCC as the comparator for

All patients who were admitted with the diagnosis of renal stone from 1965 and 1983. Cases were identified using National inpatient registry.

Retrospective cohort 1997

Chow et al.8 Sweden

Sex and age-matched subjects randomly selected from same database. Sex and agematched subjects randomly selected from same area.

(continued)

Diagnostic code from the registry.

All residents of Taiwan who were diagnosed with RCC or TCC between 2002 and 2009. Cases were identified from the Taiwan National Health insurance database. All residents of Los Angeles, New Jersey and Iowa who were diagnosed with TCC between 1983 and 1986.

Review of medical records.

2013

1997

Case–control

Taiwan

USA

Case–control

Chung et al.10

Liaw et al.21

Kidney cancer and kidney stones

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Selection: 4 stars Comparability: 1 star Exposure: 3 stars

Selection: 3 stars Comparability: 1 star Exposure: 3 stars

Selection: 2 stars Comparability: 1 star Exposure: 3 stars

Age, sex, education and area of residence

665

Selection: 3 stars Comparability: 0 star Exposure: 3 stars

Age and sex

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Selection: 4 stars Comparability: 1 star Exposure: 3 stars

Age, sex, BMI and smoking

2309

Selection: 4 stars Comparability: 1 star Outcome: 3 stars

None

NA

Selection: 2 stars Comparability: 1 star Exposure: 3 stars

Age, sex, HTN and smoking

488

472

Patient’s report (by structured interview)

the calculation of SIRs. Diagnostic code from the registry.

61 144

1997

Income, geographic area, HTN, DM, CKD, Obesity, smoking and alcohol use Selection: 4 stars Comparability: 2 stars Exposure: 3 stars

Diagnostic code from the registry (prior to the index date of having diagnosis of RCC or TCC) RCC:780 TCC:528 6540

2013

Case–control

Taiwan

USA

Case–control

Chung et al.10

Liaw et al.21

Retrospective cohort 1997

Chow et al.8 Sweden

BMI = body mass index, CKD = chronic kidney disease, DM = diabetes mellitus, HTN = hypertension, NA = not applicable, RCC = renal cell carcinoma, TCC = transitional cell carcinoma.

Selection: 3 stars Comparability: 1 star Exposure: 3 stars

None

None

Quality assessment (NewcastleOttawa scale)

227

1732

187

RCC: 489 TCC: 147 523

203

187

Number of 495 cases Number of 697 control Age Confounder adjusted

240

Patient’s report (by structured interview)

Patient’s report (by structured interview)

Patient’s report (by structured interview)

Patient’s report (by structured interview)

Patient’s report (by structured interview)

Case–control

Diagnosis of Patient’s report renal stone (by structured interview)

Case–control

Schlehofer et al.14 Australia, Denmark, Sweden and USA. Case–control 1996

Case–control

McCredie et al.12 Australia

1992

Year of publication

Case–control

Talamini et al.15 Italy

1990

1984

Study design

USA.

Maclure et al.11 USA.

1990

Case–control

Country

Ross et al.16

1989

McLaughlin et al.13 USA.

Table 1 Continued

W. Cheungpasitporn et al.

Kidney cancer and kidney stones

Figure 1. Forest plot of the included studies comparing risk of RCC between patients with a history of kidney stones and those without a history of kidney stones; square data markers represent RRs; horizontal lines, the 95% CIs with marker size reflecting the statistical weight of the study using random-effects meta-analysis. A diamond data marker represents the overall RR and 95% CI for the outcome of interest.

Figure 3. Forest plot of the included studies comparing risk of RCC in females with a history of kidney stones and those without a history of kidney stones; square data markers represent RRs; horizontal lines, the 95% CIs with marker size reflecting the statistical weight of the study using random-effects meta-analysis. A diamond data marker represents the overall RR and 95% CI for the outcome of interest.

TCC.8,10,12,16,21 Table 1 describes the detailed characteristics and quality assessment of the included studies.

The risk of RCC in patients with kidney stones The pooled risk ratio (RR) of RCC of subjects with kidney stones versus control subjects was 1.76 (95% CI, 1.24–2.49). The statistical heterogeneity

was high with an I2 of 89%. Figure 1 shows the forest plot of the included studies. In addition, a history of kidney stones was associated with increased RCC risk in males (RR, 1.41 [95% CI, 1.11–1.80], I2 = 47%), whereas the association was not significant in females (RR, 1.13 [95% CI, 0.86–1.49], I2 = 0%). Figures 2 and 3 show the forest plots of the included studies in males and females with kidney stones, respectively. Page 5 of 8

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Figure 2. Forest plot of the included studies comparing risk of RCC in males with a history of kidney stones and those without a history of kidney stones; square data markers represent RRs; horizontal lines, the 95% CIs with marker size reflecting the statistical weight of the study using random-effects meta-analysis. A diamond data marker represents the overall RR and 95% CI for the outcome of interest.

W. Cheungpasitporn et al.

Figure 4. Forest plot of the included studies comparing risk of TCC between patients with a history of kidney stones and those without a history of kidney stones; square data markers represent RRs; horizontal lines, the 95% CIs with marker size reflecting the statistical weight of the study using random-effects meta-analysis. A diamond data marker represents the overall RR and 95% CI for the outcome of interest.

The risk of TCC in patients with kidney stones

Evaluation for publication bias Funnel plots were evaluated for publication bias for the risk of RCC and TCC. The plots were suggestive to the presence of publication in favor of positive studies of the risk of RCC and negative studies of the risk of TCC in patients with kidney stones.

Discussions Our meta-analysis showed a significant association between a history of kidney stones and the two most common kidney cancers, RCC and TCC, with an overall 1.76-fold increased risk of RCC and a 2.14-fold increased risk of TCC compared with those without a history of kidney stones. In addition, our subgroup analysis found that a history of kidney stones was associated with increased RCC risk only in males but not in females. The analysis of TCC risk in males and females was not performed due to data limitations. The risk factors for kidney cancer including cigarette smoking, hypertension, obesity, acquired renal cystic disease, analgesics, genetic factors and particular occupational exposure have been established.22–24 Interestingly, our meta-analysis successfully demonstrates the association between kidney cancer and a history of kidney stones. The most likely reason for the increased risk of kidney cancer

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The pooled RR of TCC of subjects with kidney stones versus control subjects was 2.14 (95% CI, 1.35–3.40). The statistical heterogeneity was high with an I2 of 86%. Figure 4 demonstrates the forest plot of the included studies. The differences in TCC risk between males and females could not be analyzed due to data limitations.10,16,21

in patients with kidney stones is stone-induced irritation and infections. It has been proposed that kidney stones may cause changes in the local environment due to chronic irritation and infections, subsequently leading to urothelial proliferation and the development of malignant neoplasms.8,9 The inflammatory cells secrete cytokines and chemokines in response to chronic recurrent inflammation and infections, which subsequently promote the growth of neoplastic cells and progression of malignancy.25 In addition, kidney stones have also been demonstrated in animal models to cause neoplastic changes in the adjacent urothelium.26 Our study also demonstrates the association between a history of kidney stones and increased RCC risk in males in the subgroup analysis. Interestingly, the prevalence of kidney stones is higher in males than females (10.6% vs. 7.1%, respectively).27 Kidney cancers, both RCC and TCC, are also more common in male gender (RCC is about twice as common in men compared with women,28 whereas TCC is three times more prevalent in men than in women29). This underlying pathophysiology is unclear. Men with kidney stones may be exposed to dietary or environmental factors that could increase their risk of RCC. For example, men are more likely to be smokers than women and cigarette smoking was also recently reported as a potential independent risk factor for the development of kidney stones.30 Moreover, males have different eating habits from females that may contribute to both higher risks of kidney stones and RCC,31 for example females are more likely to report eating fruits and vegetables, which are less lithogenic and carcinogenic. Further studies are needed to identify the potential gender effect on kidney stones and kidney cancers. Five-year survival for patients with RCC has been improved with increased use of nephron sparing surgery (partial nephrectomy) due to the increasing number of incidentally discovered low

Kidney cancer and kidney stones

Supplementary material Supplementary material is available at QJMED online.

Acknowledgments All authors had access to the data and a role in writing the manuscript. Conflict of interest: None declared.

References 1. Goldfarb DS. Increasing prevalence of kidney stones in the United States. Kidney Int 2003; 63:1951–2. 2. Long LO, Park S. Update on nephrolithiasis management. Minerva Urol Nefrol 2007; 59:317–25. 3. Lopez M, Hoppe B. History, epidemiology and regional diversities of urolithiasis. Pediatr Nephrol 2010; 25:49–59. 4. Stamatelou KK, Francis ME, Jones CA, Nyberg LM, Curhan GC. Time trends in reported prevalence of kidney stones in the United States: 1976–1994. Kidney Int 2003; 63:1817–23. 5. Jemal A, Siegel R, Ward E, Hao Y, Xu J, Murray T, et al. Cancer statistics, 2008. CA Cancer J Clin 2008; 58:71–96. 6. Tawfiek ER, Bagley DH. Upper-tract transitional cell carcinoma. Urology 1997; 50:321–9. 7. Munoz JJ, Ellison LM. Upper tract urothelial neoplasms: incidence and survival during the last 2 decades. J Urol 2000; 164:1523–5. 8. Chow WH, Lindblad P, Gridley G, Nyre´n O, McLaughlin JK, Linet MS, et al. Risk of urinary tract cancers following kidney or ureter stones. J Natl Cancer Inst 1997; 89:1453–7. 9. Li WM, Chou YH, Li CC, Liu CC, Huang SP, Wu WJ, et al. Association of body mass index and urine pH in patients with urolithiasis. Urol Res 2009; 37:193–6. 10. Chung SD, Liu SP, Lin HC. A population-based study on the association between urinary calculi and kidney cancer. Can Urol Assoc J 2013; 7:E716–21. 11. Maclure M, Willett W. A case–control study of diet and risk of renal adenocarcinoma. Epidemiology 1990; 1:430–40. 12. McCredie M, Stewart JH. Risk factors for kidney cancer in New South Wales, Australia. II. Urologic disease, hypertension, obesity, and hormonal factors. Cancer Causes Control 1992; 3:323–31. 13. McLaughlin JK, Mandel JS, Blot WJ, Schuman LM, Mehl ES, Fraumeni JF Jr A population-based case–control study of renal cell carcinoma. J Natl Cancer Inst 1984; 72:275–84. 14. Schlehofer B, Pommer W, Mellemgaard A, Stewart JH, McCredie M, Niwa S, et al. International renal-cell-cancer study. VI. the role of medical and family history. Int J Cancer 1996; 66:723–6. 15. Talamini R, Baron AE, Barra S, Bidoli E, La Vecchia C, Negri E, et al. A case–control study of risk factor for renal cell cancer in northern Italy. Cancer Causes Control 1990; 1:125–31.

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stage tumors.32 Although kidney stones may cause inflammation in the urinary tract and increase risk for developing kidney cancers, patients with kidney stones also require more imaging studies which may detect RCC in early stages. Studies on outcome of RCC in patients with kidney stones are needed. Although most of the included studies were of high quality8,10,11,13,14,16 (as evaluated by NewcastleOttawa scale), there are some limitations. Firstly, five studies8,10,12,14,16 were conducted using medical registry-based databases, therefore coding inaccuracies for kidney stones, RCC and TCC may have been presented. Seven studies11–16,21 used a definition of kidney stones composed of self-reporting, which has been reported as accurate in 97% of cases.33 Secondly, there is statistical heterogeneity in this complete analysis. The potential sources of this heterogeneity include the difference in diagnosis methodology of kidney stones and RCC and TCC, the duration of the follow-up and the differences in confounder-adjusted methods. This is a meta-analysis of observational studies with its inherent limitations. Therefore, at best it can demonstrate an association but not a causal relationship. Most studies also lacked information regarding potential confounding factors, such as family history of kidney cancer, cigarette smoking, body mass index, dietary and occupational exposures, all of which may have contributed to the development of kidney cancer.10 Dietary factors may play an important role as a confounding factor in the association between kidney stone and kidney cancer. A high animal protein diet was not only found to be a risk factor for kidney stones, but it has also been demonstrated in a recent large cohort study of 492 186 participants recently also demonstrated that red meat intake may increase the risk of kidney cancer, especially RCC.34 Furthermore, these studies may have been vulnerable to a surveillance bias as patients with kidney stones would have been more likely to have follow-up imaging studies and kidney cancer may have been detected more than patients without kidney stones. Future studies which minimized these confounders and bias are required to confirm this potential causal relationship. In conclusion, our study demonstrates a statistically significant increased risk of RCC and TCC in patients with prior kidney stones. However, the increased risk of RCC was noted only in male patients. This finding suggests that a history of kidney stones is associated with kidney cancer and may impact clinical management and cancer surveillance.

W. Cheungpasitporn et al. 16. Ross RK, Paganini-Hill A, Landolph J, Gerkins V, Henderson BE. Analgesics, cigarette smoking, and other risk factors for cancer of the renal pelvis and ureter. Cancer Res 1989; 49:1045–8. 17. Stang A. Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol 2010; 25:603–5. 18. DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials 1986; 7:177–88. 19. Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ 2003; 327:557–60. 20. Easterbrook PJ, Berlin JA, Gopalan R, Matthews DR. Publication bias in clinical research. Lancet 1991; 337:867–72. 21. Liaw KL, Linet MS, McLaughlin JK, Yu MC, Schoenberg JB, Lynch CF, et al. Possible relation between hypertension and cancers of the renal pelvis and ureter. Int J Cancer 1997; 70:265–8. 22. Tsivian M, Moreira DM, Caso JR, Mouraviev V, Polascik TJ. Cigarette smoking is associated with advanced renal cell carcinoma. J Clin Oncol 2011; 29:2027–31. 23. Chow WH, Gridley G, Fraumeni JF Jr, Jarvholm B. Obesity, hypertension, and the risk of kidney cancer in men. N Engl J Med 2000; 343:1305–11.

25. Federico A, Morgillo F, Tuccillo C, Ciardiello F, Loguercio C. Chronic inflammation and oxidative stress in human carcinogenesis. Int J Cancer 2007; 121:2381–6. 26. Ogasawara H, Imaida K, Ishiwata H, Toyoda K, Kawanishi T, Uneyama C, et al. Urinary bladder carcinogenesis induced

27. Scales CD Jr, Smith AC, Hanley JM, Saigal CS. Prevalence of kidney stones in the United States. Eur Urol 2012; 62:160–5. 28. Siegel R, Ward E, Brawley O, Jemal A. Cancer statistics, 2011: the impact of eliminating socioeconomic and racial disparities on premature cancer deaths. CA Cancer J Clin 2011; 61:212–36. 29. Roupret M, Babjuk M, Comperat E, Zigeuner R, Sylvester R, Burger M, et al. European guidelines on upper tract urothelial carcinomas: 2013 update. Eur Urol 2013; 63:1059–71. 30. Tamadon MR, Nassaji M, Ghorbani R. Cigarette smoking and nephrolitiasis in adult individuals. Nephrourol Mon 2013; 5:702–5. 31. Wang WC, Worsley A, Hunter W. Similar but different. Health behaviour pathways differ between men and women. Appetite 2012; 58:760–6. 32. Tsui KH, van Ophoven A, Shvarts O, Belldegrun A. Nephronsparing surgery for renal cell carcinoma. Rev Urol 1999; 1:216–25. 33. Curhan GC, Willett WC, Speizer FE, Spiegelman D, Stampfer MJ. Comparison of dietary calcium with supplemental calcium and other nutrients as factors affecting the risk for kidney stones in women. Ann Intern Med 1997; 126:497–504. 34. Daniel CR, Cross AJ, Graubard BI, Park Y, Ward MH, Rothman N, et al. Large prospective investigation of meat intake, related mutagens, and risk of renal cell carcinoma. Am J Clin Nutr 2012; 95:155–62.

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24. Setiawan VW, Stram DO, Nomura AM, Kolonel LN, Henderson BE. Risk factors for renal cell cancer: the multiethnic cohort. Am J Epidemiol 2007; 166:932–40.

by melamine in F344 male rats: correlation between carcinogenicity and urolith formation. Carcinogenesis 1995; 16:2773–7.

The risk of kidney cancer in patients with kidney stones: a systematic review and meta-analysis.

The objective of this meta-analysis was to evaluate the association between a history of kidney stones and kidney cancer...
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