Skip Navigation


American Journal of Epidemiology Advance Access originally published online on July 26, 2007
American Journal of Epidemiology 2007 166(8):932-940; doi:10.1093/aje/kwm170
This Article
Right arrow Abstract Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow All Versions of this Article:
166/8/932    most recent
kwm170v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (19)
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Setiawan, V. W.
Right arrow Articles by Henderson, B. E.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Setiawan, V. W.
Right arrow Articles by Henderson, B. E.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

American Journal of Epidemiology © The Author 2007. Published by the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org.

ORIGINAL CONTRIBUTIONS

Risk Factors for Renal Cell Cancer: The Multiethnic Cohort

Veronica Wendy Setiawan1, Daniel O. Stram1, Abraham M. Y. Nomura2, Laurence N. Kolonel2 and Brian E. Henderson1

1 Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA
2 Epidemiology Program, Cancer Research Center of Hawaii, University of Hawaii, Honolulu, HI

Correspondence to Dr. V. Wendy Setiawan, Department of Preventive Medicine, University of Southern California, 1441 Eastlake Avenue, Room 4425, Los Angeles, CA 90033 (e-mail: vsetiawa{at}usc.edu).

Received for publication November 30, 2006. Accepted for publication May 9, 2007.


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 References
 
The association of body size, lifestyle, and medical conditions with renal cell cancer risk was examined among 161,126 Hawaii–Los Angeles Multiethnic Cohort participants (1993–2002). After 8.3 years of follow-up, 347 renal cell cancer cases (220 men, 127 women) were identified. Renal cell cancer risk increased with increasing body mass index in men (multivariate relative risk (RR) = 1.06 per unit of body mass index, p = 0.001) and women (RR = 1.07, p < 0.0001). The relative risks associated with being obese compared with being lean were 1.76 (95% confidence interval (CI): 1.20, 2.58) for men and 2.27 (95% CI: 1.37, 3.74) for women. Hypertension was associated with renal cell cancer (RRmen = 1.42, 95% CI: 1.07, 1.87; RRwomen = 1.58, 95% CI: 1.09, 2.28). Smoking was confirmed to be a risk factor for both sexes. Among women, diuretic use was associated with increased risk (RR = 1.63, 95% CI: 1.04, 2.57), whereas physical activity was associated with reduced risk (ptrend = 0.027). Alcohol consumption was inversely associated with risk for men (ptrend = 0.045). Compared with nondrinkers, men who drank ≥1 drinks/day had a 31% lower risk (95% CI: 0.49, 0.96). Results show that body mass index, smoking, and hypertension are risk factors for renal cell cancer in both sexes.

body mass index; body size; carcinoma, renal cell; cohort studies; diuretics; hypertension; risk factors; smoking

Abbreviations: BMI, body mass index; CI, confidence interval; RCC, renal cell cancer; RR, relative risk


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 References
 
The incidence of renal cell cancer (RCC), the most common type of kidney cancer, has been increasing globally (1, 2). In the United States, 51,200 new cases and 13,000 deaths will occur in 2007 (3). The annual increase in the RCC incidence rate between 1975 and 1995 was higher among African Americans than among Whites (men, 3.9 percent vs. 2.3 percent and women, 4.3 percent vs. 3.1 percent, respectively) (1).

Improvements in diagnosis may contribute to the rising incidence, but, in the United States, both incidence of late-stage RCC and mortality have also been increasing, implying that risk factors are contributing to this upward trend (1). Obesity, smoking, and hypertension are known risk factors for RCC (4–10). Taken together, these risk factors account for 49 percent of cases of RCC (11); thus, a large proportion remains unexplained, and the search for additional risk factors must continue.

Prospective studies assessing additional risk factors for RCC, especially in minority populations, are scarce, and their results are far from conclusive. Association between diuretics and RCC has been documented in a few prospective studies (12), but, because diuretics have been used extensively to treat hypertension, it has been difficult to separate their effects from the effects of hypertension (13). A physical activity–RCC association has been explored in several cohort studies, but results have been inconsistent (14–19). Diabetes has been shown to increase risk (20, 21), but whether the association is truly causal or confounded by obesity is unclear (4, 20). Data on alcohol consumption–RCC association from cohort studies are limited, but results suggest that increased intake is associated with lowered risk (19, 22–24).

Our goal in this study was to assess the independent effects of body size, lifestyle factors, and medical conditions on RCC risk for men and women from a multiethnic cohort study.


   MATERIALS AND METHODS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
 DISCUSSION
 References
 
Study population
The Multiethnic Cohort is a prospective study designed to identify environmental and genetic risk factors for cancer. Details of the study have been published previously (25). Briefly, recruitment began in 1993 and was completed in 1996. The cohort consists of more than 215,000 men and women (aged 45–75 years at baseline) who were mainly African Americans, Japanese, Latinos, Native Hawaiians, and Whites living in Hawaii and California. Each participant completed a self-administered mail questionnaire that inquired about diet, demographic factors, anthropometric measures, personal behaviors, medical conditions, and family history of cancer. Follow-up for cancer incidence and mortality entails active contact with the cohort members as well as passive computerized linkages to cancer registries and death certificate files in Hawaii and California. The institutional review boards at the University of Hawaii and at the University of Southern California approved the study protocol.

Incident RCC cases (International Classification of Diseases for Oncology, Second Edition, code C64.9) were identified by record linkages to the Hawaii Tumor Registry, the Cancer Surveillance Program for Los Angeles County, and the California State Cancer Registry. All registries participate in the National Cancer Institute's Surveillance, Epidemiology, and End Results Program. Deaths within the cohort were determined by annual linkage to state death certificate files and periodically to the National Death Index. Case ascertainment and death information were complete through December 31, 2002. The follow-up rate is 95 percent; National Death Index information was available for the remaining 5 percent of the cohort.

Participants with a cancer diagnosis (except for nonmelanoma skin cancer) before baseline were excluded from this analysis (n = 21,526). We also excluded subjects whose energy intake was extreme (values outside the range of mean ± 3 standard deviations) (n = 8,220). Subjects with missing information on body mass index (BMI) or an implausible BMI (outside the range of 15–50 kg/m2) and missing data on smoking status, pack-years of smoking, physical activity, diabetes, and hypertension were excluded (n = 24,953). As a result, data on 161,126 participants were available for this analysis. Excluded subjects were slightly older than those who remained in the analyses, but they were generally similar with respect to other risk factors.

Statistical analysis
Exposure data were obtained from the baseline questionnaire. BMI was investigated by using established categories for normal weight (<25 kg/m2), overweight (25–<30 kg/m2), and obese (≥30 kg/m2). Exclusion of participants whose BMI was <18.5 kg/m2 (n = 3,891) did not alter the results substantially. Weight and height were analyzed by using gender-specific quartiles. Smoking status was categorized into never, past, and current. We also analyzed smoking by using pack-years of smoking. Total intake of alcohol (grams of ethanol/day) was investigated by using a gender-specific median among drinkers (men, 10.9 g/day; women, 3.3 g/day). The physical activity questionnaire was designed to reflect a participant's behavior during an average day in the year preceding questionnaire administration. Responses to questions on hours spent, on average, each day in sleeping, sitting activities, strenuous sports, vigorous work, and light and moderate activities were aggregated into overall metabolic equivalents of activity, as previously described (26). Total physical activity (metabolic equivalents of activity per day) was then analyzed in terms of gender-specific quartiles. Physician-diagnosed hypertension, diabetes, and kidney stone were reported as yes/no on the questionnaire. Diuretic use was categorized into never/ever.

Relative risks and 95 percent confidence intervals associated with these risk factors were calculated by using Cox proportional hazards models. Age (in days) was used as the underlying time variable in the Cox regression starting with a participant's age at entry to one of these three endpoints, whichever occurred first: date of RCC diagnosis, date of death, or end of follow-up (December 31, 2002). Subjects who moved out of California and Hawaii and for whom no death information was available from the National Death Index were assumed at risk and were censored at December 31, 2002. Renal pelvis cancer cases (code C65.9, n = 46) were not included as cases, but follow-up was censored for these subjects at the date of diagnosis. Cox models were stratified by ethnicity and were performed separately for men and women. Tests for linear trend were conducted by fitting the medians of each category as continuous terms. We also calculated the relative risks of RCC for combined categories of BMI, smoking, hypertension, alcohol intake, and diuretic use; for this analysis, Cox models were stratified by sex and ethnicity and were mutually adjusted for several risk factors. The likelihood ratio test was used to test for statistical interaction between risk factors with respect to RCC. The test compares models with the main effect only with models that also include an interaction term for variables of interest. We checked the proportional hazards assumption by adding interaction terms between log (age at endpoint) and exposures of interest in Cox models, and we found no evidence of violations against the proportionality assumption.

The population attributable risk percentage was estimated by Pe(RR – 1)/RR, where Pe is the prevalence of exposure among cases and RR is the multivariate relative risk. All p values are two sided. Statistical analyses were performed with SAS 9.1 software (SAS Institute, Inc., Cary, North Carolina).


   RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
DISCUSSION
 References
 
Incident cases of RCC were diagnosed in 220 of the men and 127 of the women among 161,126 participants followed for an average of 8.3 years and a total of 1,348,881 person-years. For both sexes, the average age at diagnosis was 65 years.

Characteristics of the study population are presented in table 1. The mean age at cohort entry was 59.3 years for men and 58.8 years for women. Japanese Americans constituted the largest subgroup within each sex, followed by Whites, Latinos, African Americans, and Native Hawaiians. A majority (two thirds) of the "other" category comprises Filipinos. The prevalence of obesity was higher among women than among men (18.0 percent vs. 13.8 percent). Men were more likely than women to be current smokers, and male smokers reported higher mean pack-years compared with female smokers. Compared with women, men also consumed alcohol to a greater extent. The prevalence of hypertension was close to 40 percent in this cohort, while the prevalence of diabetes was lower at about 11 percent. The prevalence of diuretic use was higher among women than men (24.2 percent vs. 19.0 percent). Compared with women, men reported higher total physical activity and average energy intake. The prevalence of a family history of kidney cancer was low in this cohort (≤0.8 percent).


View this table:
[in this window]
[in a new window]

  		TABLE 1. Descriptive characteristics of the study population, Multiethnic Cohort Study, Hawaii and California, 1993–2002

 
Table 2 shows the associations of body size and physical activity with RCC risk. BMI was positively associated with risk for both sexes. The multivariate relative risks associated with a one-unit increase in BMI were 1.06 (95 percent confidence interval (CI): 1.02, 1.09; ptrend = 0.001) for men and 1.07 (95 percent CI: 1.04, 1.10; ptrend < 0.0001) for women. Compared with a BMI of <25 kg/m2, overweight was associated with a twofold (95 percent CI: 1.31, 3.15) increased risk for women. Overweight status, however, was not associated with RCC in men (RR = 1.14, 95 percent CI: 0.84, 1.55). Obesity was associated with increased risk for men (RR = 1.76, 95 percent CI: 1.20, 2.58) and women (RR = 2.27, 95 percent CI: 1.37, 3.74). Although the association appeared stronger in women than in men, the statistical testing showed no evidence of interaction between sex and BMI (p = 0.318).


View this table:
[in this window]
[in a new window]

  		TABLE 2. Association between body size, physical activity, and renal cell cancer in men and women, Multiethnic Cohort Study, Hawaii and California, 1993–2002

 
Weight was positively associated with RCC risk for both sexes. In the multivariate analysis, the relative risks in the highest versus lowest quartile of weight were 1.52 (95 percent CI: 0.84, 2.75, ptrend = 0.005) for men and 3.39 (95 percent CI: 1.71, 6.72, ptrend < 0.0001) for women. No significant interaction between sex and weight was observed (p = 0.254). After adjustment for weight and other risk factors, height did not show a statistically significant trend in RCC risk for either men or women. We also assessed the association between RCC and the following factors: BMI and weight at age 21 years and weight change (between age 21 years and baseline); none of these factors were significantly associated with risk after BMI/weight at baseline was included in the model (data not shown).

We observed an inverse association between total physical activity and RCC among women (ptrend = 0.027) even after adjustment for BMI and other risk factors, but not among men (ptrend = 0.806) (table 2). The test for interaction between sex and physical activity was borderline significant (p = 0.074). The separate analysis of either moderate or vigorous physical activity showed no significant association with risk (results not shown).

Associations of smoking and alcohol consumption with RCC are shown in table 3. Smoking was related to increased RCC risk for both sexes. For men, a significant increase in risk was observed among past smokers (RR = 1.51, 95 percent CI: 1.08, 2.11) and current smokers (RR = 2.30, 95 percent CI: 1.55, 3.41). A significant dose-response trend with pack-years of smoking was observed (ptrend < 0.001), and men who were current smokers and had smoked for >20 pack-years had a 2.3-fold (95 percent CI: 1.41, 3.62) increased risk compared with nonsmokers. Among women, current smoking status was significantly associated with risk (RR = 1.71, 95 percent CI: 1.04, 2.82). Although the trend was not as strong as for men, a dose-response relation with pack-years was also observed for women (ptrend = 0.022).


View this table:
[in this window]
[in a new window]

  		TABLE 3. Association between cigarette smoking, alcohol consumption, and renal cell cancer in men and women, Multiethnic Cohort Study, Hawaii and California, 1993–2002

 
In the multivariate analysis, alcohol consumption was associated with a decreased RCC risk for men (ptrend = 0.045) (table 3). Men who drank at least 11 g/day of ethanol (~1 drink/day) had a 31 percent lower risk (95 percent CI: 0.49, 0.96) compared with those who did not drink. Alcohol–RCC association among women was not as obvious; the trend was not significant (ptrend = 0.502), but, compared with nondrinkers, drinkers had relative risks of less than 1. No evidence of statistical interaction between sex and alcohol drinking was observed. We also examined the associations with specific alcoholic beverages (beer, wine, and hard liquor) and did not observe a significant association for any individual beverage type (results not shown).

Table 4 shows the association between medical conditions, diuretic use, and RCC. In the multivariate analyses, hypertension was associated with increased risk (RRmen = 1.42, 95 percent CI: 1.07, 1.87; RRwomen = 1.58, 95 percent CI: 1.09, 2.28). To address the possibility that hypertension might be caused by RCC, we repeated our analysis by using a 2-year lag (i.e., cases occurring during the first 2 years of follow-up were excluded from the analysis). The number of cases was reduced to 280 (181 men and 99 women), but the magnitude of the association was similar (RRmen = 1.34, 95 percent CI: 0.99, 1.82; RRwomen = 1.51, 95 percent CI: 0.99, 2.29). Among men, after adjustment for other risk factors, no association with ever use of diuretics was observed (RR = 1.06, 95 percent CI: 0.74, 1.52). Among women, the association was significant (RR = 1.63, 95 percent CI: 1.04, 2.57) and was more apparent among normotensive and nonobese women (RR = 2.54, 95 percent CI: 1.06, 6.05). In the age-adjusted analysis, diabetes was associated with increased risk for both sexes, but, in the multivariate analysis, the associations were attenuated and became nonsignificant. A diagnosis of kidney stone was not associated with RCC in either sex.


View this table:
[in this window]
[in a new window]

  		TABLE 4. Association between medical conditions, diuretic use, and renal cell cancer in men and women, Multiethnic Cohort Study, Hawaii and California, 1993–2002

 
We examined the joint effects of BMI with smoking, hypertension, or diuretic use (figure 1). RCC risk for obese individuals who smoked was 3.56 (95 percent CI: 2.26, 5.61) compared with that for lean individuals who never smoked. Risk for obese and hypertensive individuals was 2.82 (95 percent CI: 1.97, 4.02) compared with that for lean and normotensive subjects. Obese individuals who used diuretics had a 2.34 times higher risk (95 percent CI: 1.55, 3.54) than lean nonusers did. We also assessed the joint effects of smoking with alcohol intake or hypertension (figure 2). Compared with normotensive nonsmokers, hypertensive smokers had a 2.49 times higher risk of RCC (95 percent CI: 1.74, 3.55). Interestingly, smokers who did not drink alcohol had the highest risk (RR = 1.93, 95 percent CI: 1.16, 3.24). None of the interactions was significant (p ≥ 0.097).


Figure 1
View larger version (13K):
[in this window]
[in a new window]
[Download PowerPoint slide]
  		FIGURE 1. Joint effects of body mass index (BMI; weight (kg)/height (m2)) with smoking, hypertension, or diuretics use. Relative risks (RRs; shown above the bars) were derived from Cox models stratified by sex and ethnicity and adjusted for smoking status, hypertension, alcohol intake, and physical activity as appropriate, Multiethnic Cohort Study, Hawaii and California, 1993–2002.

 

Figure 2
View larger version (12K):
[in this window]
[in a new window]
[Download PowerPoint slide]
  		FIGURE 2. Joint effects of smoking with hypertension or alcohol intake. Relative risks (RRs; shown above the bars) were derived from Cox models stratified by sex and ethnicity and adjusted for body mass index, hypertension, alcohol intake, and physical activity as appropriate, Multiethnic Cohort Study, Hawaii and California, 1993–2002.

 
Restricting our analysis to cases with a clear cell subtype (n = 293) did not alter the observed associations with each risk factor tested. In addition, the associations did not vary by stage of diagnosis (localized or advanced). We also assessed ethnic-specific associations of smoking, obesity, and hypertension with RCC. Despite being limited by small numbers of cases, the associations were consistent across ethnicity (data not shown).

Finally, we estimated that in our cohort, 32 percent, 10 percent, and 15 percent of RCC in male cases and 16 percent, 17 percent, and 24 percent of RCC in female cases could be attributed to ever smoking, obesity, and hypertension, respectively. Overall, these risk factors accounted for at least half of cases of RCC in the cohort.


   DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
References
 
In this large multiethnic cohort, we confirmed that BMI, smoking, and hypertension are independent risk factors for RCC in men and women. We observed a significant increase in risk associated with diuretic use among women, even after correcting for the presence of hypertension. Furthermore, we observed a protective effect of physical activity among women and of alcohol drinking among men.

The most consistent finding in epidemiologic studies of RCC is the excess risk for individuals who are smokers, obese, and hypertensive (4). We confirmed that smoking is an independent risk factor for RCC in men and women. We also found that RCC risk increased with BMI for both sexes. To our knowledge, five cohort studies with more than 200 cases have investigated BMI as a risk factor for RCC (8, 9, 18, 27, 28), and they all showed a higher risk of RCC with increasing BMI. The proposed mechanisms by which obesity affects risk include changes in hormonal patterns (increased levels of insulin, insulin-like growth factors, and estrogens), increased glomerular filtration rate and renal plasma flow, and increased lipid peroxidation of the proximal renal tubules (5, 29).

As observed in our study, previous studies have reported that the magnitude of association between BMI and RCC is greater among women than among men (9, 28). Among females in our cohort, an elevated risk was observed starting with a BMI of >25 kg/m2, whereas, among men, elevated risk was apparent among only those with a BMI of ≥30 kg/m2. We also observed that the relative risk associated with being obese was greater for women (RR = 2.3) than for men (RR = 1.8), although the test for interaction was not significant. Bergström et al. (5) have suggested that the gender differences in the BMI–RCC association observed in some studies can be explained by the different distribution of BMI among men and women within categories; for example, women are usually more obese than men in the highest category of BMI. In our cohort, mean BMI in the obese category was higher in women (34.6 kg/m2) than in men (33.4 kg/m2), but our results did not change when we excluded from our analyses subjects whose BMI was >35 kg/m2 (n = 7,750). Despite the fact that the number of cases in our study was rather small to make a definite comparison between genders, our findings suggest that the threshold for an effect of BMI on risk is lower for women than for men.

In our study, hypertension was independently associated with RCC in both sexes. The biologic mechanism by which hypertension affects risk is unclear; it has been hypothesized that lipid peroxidation, which is increased in hypertensive individuals and has been linked to tumor development, might be partly responsible for the increased RCC risk (29).

Consistent with results from other cohort studies (7, 9, 12), we found that women were at a higher risk of RCC associated with diuretic use than were men, even after correcting for the presence of hypertension. Several case-control studies have shown that diuretic use remained significantly associated with increased risk for female nonhypertensives (30–33). We observed that the association was even stronger among normotensive and nonobese women, which suggests that diuretic use could be an independent risk factor for RCC. The association between use of diuretics and RCC has some biologic plausibility, since diuretics affect renal tubular cells, the site of origin of RCC (34). However, the reasons why women are at higher diuretic-associated risk than are men are unknown. Possible explanations have been proposed, including a higher prevalence and intensity of diuretic use among women than among men (total chemical burden to the tubular cells may be important in determining carcinogenicity) (34) and higher estrogen exposure in women (estrogens have been shown to enhance the effect of diuretics in renal tubules in animal models) (35). Interestingly, we observed a stronger association among current users of hormone replacement therapy (RR = 2.57, 95 percent CI: 1.17, 5.64) than among nonusers (RR = 1.15, 95 percent CI: 0.59, 2.21), which supports the latter hypothesis.

A role of physical activity in the development of RCC is plausible, since energy expenditure is an important determinant of obesity. However, the epidemiologic evidence of an association between physical activity and RCC is weak. Of five cohort studies that investigated this association (15–19), two found a protective effect with increased occupational (15) and recreational (17) physical activity. After adjusting for BMI, we found that total physical activity was associated with a reduced risk for women but not for men. Whether this gender disparity has a true biologic explanation or is caused by residual confounding is unclear. It is possible that we did not completely eliminate the effect of BMI given that BMI is a stronger risk factor for women than for men and that, generally, women with a higher BMI engage in less physical activity than lean women do, and vice versa. Further studies are warranted to confirm our findings.

A growing number of cohort studies have reported a protective effect of alcohol drinking on RCC risk for men (23), women (19, 22, 36), or both (24). In our study, alcohol drinking was protective for men. It is possible that we did not have sufficient power to detect a significant relation for women because so few of them reported drinking alcohol. Among White women who reported the highest rate of alcohol drinking in the cohort, no significant association and dose response was observed, suggesting that alcohol may not be a strong risk factor for women. The mechanism of action by which alcohol reduces RCC risk is not established. Obesity, a known RCC risk factor, increases insulin resistance, and alcohol improves insulin sensitivity (24). Our results contributed further evidence that alcohol is protective, but additional studies are needed to solidify alcohol as an independent protective factor for RCC.

Our study has several strengths and limitations. The strengths include its prospective design, exclusion of subjects with cancer at baseline, and the ability to include most risk factors for RCC. One limitation of this study is that, despite its large size, because of the rarity of RCC, we had relatively small numbers of cases in certain risk factor categories, so some relative risks did not reach statistical significance that might have otherwise. Another limitation is that our analyses were based on exposures collected at baseline and did not consider changes during follow-up. Lastly, although the physical activity questionnaire has not been fully validated in our study population against a "gold standard," it has been pretested to assure that subjects could understand the questions, compared favorably with a different survey instrument administered to an overlapping set of subjects (25), and is comprehensive.

In conclusion, we confirmed that BMI, smoking, and hypertension are independent risk factors for RCC. We estimated that at least half of the cases of RCC in this cohort might have been prevented by eliminating these risk factors. Despite the compelling epidemiologic evidence, no credible mechanistic hypothesis for the association between these risk factors and RCC has been tested. Future studies incorporating biologic markers are warranted to understand the mechanisms underlying these associations.


   ACKNOWLEDGMENTS
 
This work is supported by National Cancer Institute grant CA54281. V. W. S. is supported by a Career Development Award from the National Cancer Institute (CA116543).

The authors thank Dr. Lynne Wilkens, Dr. Kristine Monroe, and Peggy Wan for their support with the data management and analysis.

Conflict of interest: none declared.


   References
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 References
 

  1. Chow WH, Devesa SS, Warren JL, et al. Rising incidence of renal cell cancer in the United States. JAMA (1999) 281:1628–31.[Abstract/Free Full Text]
  2. Mathew A, Devesa SS, Fraumeni JF Jr, et al. Global increases in kidney cancer incidence, 1973 –1992. Eur J Cancer Prev (2002) 11:171–8.[CrossRef][Web of Science][Medline]
  3. American Cancer Society. Cancer facts & figures 2007 (2007) Atlanta, GA: American Cancer Society.
  4. Moore LE, Wilson RT, Campleman SL. Lifestyle factors, exposures, genetic susceptibility, and renal cell cancer risk: a review. Cancer Invest (2005) 23:240–55.[Web of Science][Medline]
  5. Bergström A, Hsieh CC, Lindblad P, et al. Obesity and renal cell cancer—a quantitative review. Br J Cancer (2001) 85:984–90.[CrossRef][Web of Science][Medline]
  6. Hunt JD, van der Hel OL, McMillan GP, et al. Renal cell carcinoma in relation to cigarette smoking: meta-analysis of 24 studies. Int J Cancer (2005) 114:101–8.[CrossRef][Web of Science][Medline]
  7. Heath CW Jr, Lally CA, Calle EE, et al. Hypertension, diuretics, and antihypertensive medications as possible risk factors for renal cell cancer. Am J Epidemiol (1997) 145:607–13.[Abstract/Free Full Text]
  8. Chow WH, Gridley G, Fraumeni JF Jr, et al. Obesity, hypertension, and the risk of kidney cancer in men. N Engl J Med (2000) 343:1305–11.[Abstract/Free Full Text]
  9. Flaherty KT, Fuchs CS, Colditz GA, et al. A prospective study of body mass index, hypertension, and smoking and the risk of renal cell carcinoma (United States). Cancer Causes Control (2005) 16:1099–106.[CrossRef][Web of Science][Medline]
  10. Schouten LJ, van Dijk BA, Oosterwijk E, et al. Hypertension, antihypertensives and mutations in the Von Hippel-Lindau gene in renal cell carcinoma: results from the Netherlands Cohort Study. J Hypertens (2005) 23:1997–2004.[Web of Science][Medline]
  11. Benichou J, Chow WH, McLaughlin JK, et al. Population attributable risk of renal cell cancer in Minnesota. Am J Epidemiol (1998) 148:424–30.[Abstract/Free Full Text]
  12. Grossman E, Messerli FH, Goldbourt U. Antihypertensive therapy and the risk of malignancies. Eur Heart J (2001) 22:1343–52.[Abstract/Free Full Text]
  13. Messerli FH. Risk factors for renal cell carcinoma: hypertension or diuretics? Kidney Int (2005) 67:774–5.[CrossRef][Web of Science][Medline]
  14. Paffenbarger RS Jr, Hyde RT, Wing AL. Physical activity and incidence of cancer in diverse populations: a preliminary report. Am J Clin Nutr (1987) 45:312–17.[Free Full Text]
  15. Bergström A, Moradi T, Lindblad P, et al. Occupational physical activity and renal cell cancer: a nationwide cohort study in Sweden. Int J Cancer (1999) 83:186–91.[CrossRef][Web of Science][Medline]
  16. Bergström A, Terry P, Lindblad P, et al. Physical activity and risk of renal cell cancer. Int J Cancer (2001) 92:155–7.[CrossRef][Web of Science][Medline]
  17. Mahabir S, Leitzmann MF, Pietinen P, et al. Physical activity and renal cell cancer risk in a cohort of male smokers. Int J Cancer (2004) 108:600–5.[CrossRef][Web of Science][Medline]
  18. van Dijk BA, Schouten LJ, Kiemeney LA, et al. Relation of height, body mass, energy intake, and physical activity to risk of renal cell carcinoma: results from the Netherlands Cohort Study. Am J Epidemiol (2004) 160:1159–67.[Abstract/Free Full Text]
  19. Nicodemus KK, Sweeney C, Folsom AR. Evaluation of dietary, medical and lifestyle risk factors for incident kidney cancer in postmenopausal women. Int J Cancer (2004) 108:115–21.[CrossRef][Web of Science][Medline]
  20. Wideroff L, Gridley G, Mellemkjaer L, et al. Cancer incidence in a population-based cohort of patients hospitalized with diabetes mellitus in Denmark. J Natl Cancer Inst (1997) 89:1360–5.[Abstract/Free Full Text]
  21. Lindblad P, Chow WH, Chan J, et al. The role of diabetes mellitus in the aetiology of renal cell cancer. Diabetologia (1999) 42:107–12.[CrossRef][Web of Science][Medline]
  22. Rashidkhani B, Akesson A, Lindblad P, et al. Alcohol consumption and risk of renal cell carcinoma: a prospective study of Swedish women. Int J Cancer (2005) 117:848–53.[CrossRef][Web of Science][Medline]
  23. Mahabir S, Leitzmann MF, Virtanen MJ, et al. Prospective study of alcohol drinking and renal cell cancer risk in a cohort of Finnish male smokers. Cancer Epidemiol Biomarkers Prev (2005) 14:170–5.[Abstract/Free Full Text]
  24. Lee JE, Giovannucci E, Smith-Warner SA, et al. Total fluid intake and use of individual beverages and risk of renal cell cancer in two large cohorts. Cancer Epidemiol Biomarkers Prev (2006) 15:1204–11.[Abstract/Free Full Text]
  25. Kolonel LN, Henderson BE, Hankin JH, et al. A multiethnic cohort in Hawaii and Los Angeles: baseline characteristics. Am J Epidemiol (2000) 151:346–57.[Abstract/Free Full Text]
  26. Nöthlings U, Wilkens LR, Murphy SP, et al. Body mass index and physical activity as risk factors for pancreatic cancer: the Multiethnic Cohort Study. Cancer Causes Control (2007) 18:165–75.[CrossRef][Web of Science][Medline]
  27. Bjørge T, Tretli S, Engeland A. Relation of height and body mass index to renal cell carcinoma in two million Norwegian men and women. Am J Epidemiol (2004) 160:1168–76.[Abstract/Free Full Text]
  28. Pischon T, Lahmann PH, Boeing H, et al. Body size and risk of renal cell carcinoma in the European Prospective Investigation into Cancer and Nutrition (EPIC). Int J Cancer (2006) 118:728–38.[CrossRef][Web of Science][Medline]
  29. Gago-Dominguez M, Castelao JE. Lipid peroxidation and renal cell carcinoma: further supportive evidence and new mechanistic insights. Free Radic Biol Med (2006) 40:721–33.[CrossRef][Web of Science][Medline]
  30. Yu MC, Mack TM, Hanisch R, et al. Cigarette smoking, obesity, diuretic use, and coffee consumption as risk factors for renal cell carcinoma. J Natl Cancer Inst (1986) 77:351–6.[Web of Science][Medline]
  31. McLaughlin JK, Blot WJ, Fraumeni JF Jr. Diuretics and renal cell cancer. J Natl Cancer Inst (1988) 80:378.[Free Full Text]
  32. Mellemgaard A, Moller H, Olsen JH. Diuretics may increase risk of renal cell carcinoma. Cancer Causes Control (1992) 3:309–12.[CrossRef][Web of Science][Medline]
  33. Kreiger N, Marrett LD, Dodds L, et al. Risk factors for renal cell carcinoma: results of a population-based case-control study. Cancer Causes Control (1993) 4:101–10.[CrossRef][Web of Science][Medline]
  34. Messerli FH. Diuretic therapy and renal cell carcinoma—another controversy? Eur Heart J (1999) 20:1441–2.[Free Full Text]
  35. Verlander JW, Tran TM, Zhang L, et al. Estradiol enhances thiazide-sensitive NaCl cotransporter density in the apical plasma membrane of the distal convoluted tubule in ovariectomized rats. J Clin Invest (1998) 101:1661–9.[Web of Science][Medline]
  36. Prineas RJ, Folsom AR, Zhang ZM, et al. Nutrition and other risk factors for renal cell carcinoma in postmenopausal women. Epidemiology (1997) 8:31–6.[Web of Science][Medline]

Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 Cancer Epidemiol. Biomarkers Prev.Home page
V. W. Setiawan, L. N. Kolonel, and B. E. Henderson
Menstrual and Reproductive Factors and Risk of Renal Cell Cancer in the Multiethnic Cohort
Cancer Epidemiol. Biomarkers Prev., January 1, 2009; 18(1): 337 - 340.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Epidemiol. Biomarkers Prev.Home page
L. J. Schouten, B. A.C. van Dijk, E. Oosterwijk, M. van Engeland, C. A. Hulsbergen-van de Kaa, L. A.L.M. Kiemeney, R. A. Goldbohm, A. Kester, S. de Vogel, J. A. Schalken, et al.
Alcohol Consumption and Mutations or Promoter Hypermethylation of the von Hippel-Lindau Gene in Renal Cell Carcinoma
Cancer Epidemiol. Biomarkers Prev., December 1, 2008; 17(12): 3543 - 3550.
[Abstract] [Full Text] [PDF]

Home page
 CarcinogenesisHome page
J. Lin, X. Pu, W. Wang, S. Matin, N. M. Tannir, C. G. Wood, and X. Wu
Case-control analysis of nucleotide excision repair pathway and the risk of renal cell carcinoma
Carcinogenesis, November 1, 2008; 29(11): 2112 - 2119.
[Abstract] [Full Text] [PDF]

Home page
 Am J EpidemiolHome page
K. F. Adams, M. F. Leitzmann, D. Albanes, V. Kipnis, S. C. Moore, A. Schatzkin, and W.-H. Chow
Body Size and Renal Cell Cancer Incidence in a Large US Cohort Study
Am. J. Epidemiol., August 1, 2008; 168(3): 268 - 277.
[Abstract] [Full Text] [PDF]

Home page
 Am J EpidemiolHome page
S. C. Moore, W.-H. Chow, A. Schatzkin, K. F. Adams, Y. Park, R. Ballard-Barbash, A. Hollenbeck, and M. F. Leitzmann
Physical Activity during Adulthood and Adolescence in Relation to Renal Cell Cancer
Am. J. Epidemiol., July 15, 2008; 168(2): 149 - 157.
[Abstract] [Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow All Versions of this Article:
166/8/932    most recent
kwm170v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (19)
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Setiawan, V. W.
Right arrow Articles by Henderson, B. E.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Setiawan, V. W.
Right arrow Articles by Henderson, B. E.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?