Background:

Renal cell carcinoma (RCC) accounts for more than 80% of kidney cancers in adults, and obesity is a known risk factor. Regular consumption of sweetened beverages has been linked to obesity and several chronic diseases, including some types of cancer. It is uncertain whether soft drink and juice consumption is associated with risk of RCC. We investigated the associations of soft drink and juice consumption with RCC incidence and mortality in the European Prospective Investigation into Cancer and Nutrition (EPIC).

Methods:

A total of 389,220 EPIC participants with median age of 52 years at recruitment (1991–2000) were included. Cox regression yielded adjusted HRs and 95% confidence intervals (CI) for RCC incidence and mortality in relation to intakes of juices and total, sugar-sweetened, and artificially sweetened soft drinks.

Results:

A total of 888 incident RCCs and 356 RCC deaths were identified. In models including adjustment for body mass index and energy intake, there was no higher risk of incident RCC associated with consumption of juices (HR per 100 g/day increment = 1.03; 95% CI, 0.97–1.09), total soft drinks (HR = 1.01; 95% CI, 0.98–1.05), sugar-sweetened soft drinks (HR = 0.99; 95% CI, 0.94–1.05), or artificially sweetened soft drinks (HR = 1.02; 95% CI, 0.96–1.08). In these fully adjusted models, none of the beverages was associated with RCC mortality (HR, 95% CI per 100 g/day increment 1.06, 0.97–1.16; 1.03, 0.98–1.09; 0.97, 0.89–1.07; and 1.06, 0.99–1.14, respectively).

Conclusions:

Consumption of juices or soft drinks was not associated with RCC incidence or mortality after adjusting for obesity.

Impact:

Soft drink and juice intakes are unlikely to play an independent role in RCC development or mortality.

Consumption of sweet beverages such as soft drinks and juices has been rising worldwide (1). These beverages contribute to adiposity (1, 2) and contain additives and chemical contaminants from food packaging that might have carcinogenic properties (3). Sweetened beverage consumption has been suggested to be associated with the incidence of obesity-related cancers such as kidney cancer, but results from epidemiological studies are inconclusive (4–6), and kidney cancer mortality remains unexplored.

We investigated soft drink and juice consumption in relation to renal cell carcinoma (RCC) incidence and mortality in the European Prospective Investigation into Cancer and Nutrition (EPIC).

Participants

EPIC is a prospective cohort study of >520,000 participants aged 30–70 years, recruited between 1991 and 2000 in 10 European countries. At recruitment, data on diet, lifestyle, medical history, anthropometric measurements, and blood samples were collected (7). All participants provided written informed consent and the study was approved by the ethics committees of the International Agency for Research on Cancer (IARC) and each participating center.

Soft drink and juice consumption

Baseline soft drink and juice consumption was mostly assessed by diet questionnaires covering the past year (7). Total soft drinks combined carbonated/soft/isotonic drinks and diluted syrups, and was subdivided into sugar-sweetened and artificially sweetened soft drinks. Types of soft drinks were unmeasured in Italy, Spain, and Umeå (Sweden), and these centers were excluded from this part of the analyses. Juices comprised fruit and vegetable juices and nectars.

Ascertainment of cases

Cancer cases and deaths were ascertained through linkage to population registries or active follow-up, depending on the study center. RCC was defined as ICD-10 C64. Participants were followed from recruitment until date of first invasive cancer diagnosis (for RCC incidence analyses), death, emigration, or end of follow-up, whichever occurred first.

Statistical analysis

Multivariable Cox regression models with age as the timescale were used to estimate HRs and 95% confidence intervals (CI) for RCC incidence and mortality in relation to intakes of juices and total, sugar-sweetened, and artificially sweetened soft drinks modeled continuously (per 100 g/day increment) and as 3-knot restricted cubic splines. Models were stratified by sex and country and adjusted for age at recruitment, education, smoking status, alcohol consumption, physical activity, juice intake (for soft drink analyses), and total soft drink intake (for juice analyses). Models for sugar-sweetened and artificially sweetened soft drinks were mutually adjusted. Separate models additionally adjusted for body mass index (BMI) and total energy intake. Interactions with sex were evaluated with likelihood ratio tests. Sensitivity analyses were performed additionally adjusting for fruit and vegetable intake, excluding the first 2 years of follow-up, and excluding participants with self-reported diabetes at baseline. All analyses were conducted using Stata 13.1 (StataCorp).

Availability of data and materials

For information on how to submit an application for gaining access to EPIC data and/or biospecimens, please follow the instructions at http://epic.iarc.fr/access/index.php.

A total of 389,220 participants with complete data were included, in whom 888 incident RCCs and 356 RCC deaths occurred during a mean follow-up of 15 years for incidence and 16 years for mortality (range, 0–22.8 years). Table 1 displays characteristics of participants.

Table 1.

Characteristics of EPIC participants included in analyses of soft drink and juice consumption and risk of renal cell carcinoma.

WomenMenOverall
TotalIncident RCC casesTotalIncident RCC casesTotalIncident RCC cases
N 264,652 373 124,568 515 389,220 888 
Age (years), median (IQR) 51.4 (45.0–58.0) 57.1 (50.7–62.1) 52.7 (46.2–59.2) 56.0 (50.8–61.2) 51.8 (45.3–58.5) 56.5 (50.8–61.5) 
Countrya, % (n      
 Denmark 10.8 (28,596) 16.6 (62) 21.0 (26,171) 24.1 (124) 14.1 (54,767) 21.0 (186) 
 France 23.1 (61,105) 1.1 (4) 0 (0) 0 (0) 15.7 (61,105) 0.5 (4) 
 Germany 10.3 (27,316) 14.5 (54) 17.0 (21,122) 20.8 (107) 12.4 (48,438) 18.1 (161) 
 Italy 11.5 (30,465) 18.5 (69) 11.1 (13,785) 11.3 (58) 11.4 (44,250) 14.3 (127) 
 The Netherlands 9.1 (24,087) 12.9 (48) 5.9 (7,388) 2.1 (11) 8.1 (31,475) 6.6 (59) 
 Spain 9.3 (24,645) 10.5 (39) 12.1 (15,051) 15.5 (80) 10.2 (39,696) 13.4 (119) 
 Sweden 9.9 (26,098) 14.5 (54) 17.6 (21,949) 16.1 (83) 12.3 (48,047) 15.4 (137) 
 United Kingdom 16.0 (42,340) 11.5 (43) 15.3 (19,102) 10.1 (52) 15.8 (61,442) 10.7 (95) 
Education level, % (n      
 None/primary school 28.6 (75,751) 46.9 (175) 33.2 (41,410) 38.4 (198) 30.1 (117,161) 42.0 (373) 
 Technical/professional school 21.8 (57,741) 27.1 (101) 25.3 (31,495) 21.6 (111) 22.9 (89,236) 23.9 (212) 
 Secondary school 24.2 (63,992) 12.3 (46) 13.5 (16,864) 14.4 (74) 20.8 (80,856) 13.5 (120) 
 Longer education 25.4 (67,168) 13.7 (51) 27.9 (34,799) 25.6 (132) 26.2 (101,967) 20.6 (183) 
Smoking status, % (n      
 Never 58.7 (155,273) 54.4 (203) 34.0 (42,410) 26.2 (135) 50.8 (197,683) 38.1 (338) 
 Former 22.7 (60,121) 20.1 (75) 37.0 (46,030) 37.7 (194) 27.3 (106,151) 30.3 (269) 
 Current 18.6 (49,258) 25.5 (95) 29.0 (36,128) 36.1 (186) 21.9 (85,386) 31.6 (281) 
Physical activity, % (n      
 Inactive 22.3 (58,926) 26.5 (99) 17.6 (21,923) 20.6 (106) 20.8 (80,849) 23.1 (205) 
 Moderately inactive 36.3 (96,167) 37.5 (140) 31.8 (39,601) 37.9 (195) 34.9 (135,768) 37.7 (335) 
 Moderately active 24.7 (65,315) 17.4 (65) 24.8 (30,892) 22.7 (117) 24.7 (96,207) 20.5 (182) 
 Active 16.7 (44,244) 18.5 (69) 25.8 (32,152) 18.8 (97) 19.6 (76,396) 18.7 (166) 
Hypertensionb, % (n17.8 (47,199) 29.8 (111) 20.2 (25,108) 30.5 (157) 18.6 (72,307) 30.2 (268) 
Diabetesb, % (n2.1 (5,577) 3.8 (14) 3.4 (4,176) 4.7 (24) 2.5 (9,753) 4.3 (38) 
BMI (kg/m2), median (IQR) 24.0 (21.8–27.1) 25.6 (23.2–28.9) 26.1 (24.0–28.5) 27.1 (24.8–29.7) 24.8 (22.4–27.7) 26.5 (24.2–29.5) 
Alcohol intake (g/day), median (IQR) 4.2 (0.6–12.1) 1.8 (0.2–8.7) 12.9 (4.2–30.2) 13.6 (4.4–31.7) 6.4 (1.1–16.7) 7.5 (1.0–22.4) 
Energy intake (kcal/day), median (IQR) 1,907.7 (1,580.6–2,293.2) 1,806.2 (1,496.6–2,207.5) 2,356.8 (1,953.3–2,818.4) 2,341.6 (1,986.0–2,791.0) 2,038.3 (1,669.2–2,478.1) 2,119.5 (1,724.6–2,578.0) 
Fruit and vegetable juice intake (g/day), median (IQR)c 47.1 (10.7–120.0) 35.7 (8.3–120.0) 32.1 (8.3–101.9) 28.6 (8.2–103.4) 42.9 (9.0–120.0) 33.3 (8.3–120.0) 
Total soft drink intake (g/day), median (IQR)c 41.9 (13.4–138.5) 56.0 (14.8–175.5) 62.6 (19.7–194.9) 71.4 (16.4–157.1) 48.6 (16.4–157.1) 63.4 (16.4–171.4) 
Sugar-sweetened soft drink intake (g/day), median (IQR)c,d 28.6 (4.8–107.1) 31.5 (12.2–117.0) 45.5 (14.0–153.5) 46.3 (7.3–127.5) 32.1 (6.6–113.2) 35.4 (8.6–121.4) 
Artificially sweetened soft drink intake (g/day), median (IQR)c,d 14.3 (2.0–85.7) 21.8 (6.6–103.8) 16.4 (3.3–85.7) 16.4 (3.3–89.0) 14.3 (2.0–85.7) 19.7 (6.5–92.3) 
WomenMenOverall
TotalIncident RCC casesTotalIncident RCC casesTotalIncident RCC cases
N 264,652 373 124,568 515 389,220 888 
Age (years), median (IQR) 51.4 (45.0–58.0) 57.1 (50.7–62.1) 52.7 (46.2–59.2) 56.0 (50.8–61.2) 51.8 (45.3–58.5) 56.5 (50.8–61.5) 
Countrya, % (n      
 Denmark 10.8 (28,596) 16.6 (62) 21.0 (26,171) 24.1 (124) 14.1 (54,767) 21.0 (186) 
 France 23.1 (61,105) 1.1 (4) 0 (0) 0 (0) 15.7 (61,105) 0.5 (4) 
 Germany 10.3 (27,316) 14.5 (54) 17.0 (21,122) 20.8 (107) 12.4 (48,438) 18.1 (161) 
 Italy 11.5 (30,465) 18.5 (69) 11.1 (13,785) 11.3 (58) 11.4 (44,250) 14.3 (127) 
 The Netherlands 9.1 (24,087) 12.9 (48) 5.9 (7,388) 2.1 (11) 8.1 (31,475) 6.6 (59) 
 Spain 9.3 (24,645) 10.5 (39) 12.1 (15,051) 15.5 (80) 10.2 (39,696) 13.4 (119) 
 Sweden 9.9 (26,098) 14.5 (54) 17.6 (21,949) 16.1 (83) 12.3 (48,047) 15.4 (137) 
 United Kingdom 16.0 (42,340) 11.5 (43) 15.3 (19,102) 10.1 (52) 15.8 (61,442) 10.7 (95) 
Education level, % (n      
 None/primary school 28.6 (75,751) 46.9 (175) 33.2 (41,410) 38.4 (198) 30.1 (117,161) 42.0 (373) 
 Technical/professional school 21.8 (57,741) 27.1 (101) 25.3 (31,495) 21.6 (111) 22.9 (89,236) 23.9 (212) 
 Secondary school 24.2 (63,992) 12.3 (46) 13.5 (16,864) 14.4 (74) 20.8 (80,856) 13.5 (120) 
 Longer education 25.4 (67,168) 13.7 (51) 27.9 (34,799) 25.6 (132) 26.2 (101,967) 20.6 (183) 
Smoking status, % (n      
 Never 58.7 (155,273) 54.4 (203) 34.0 (42,410) 26.2 (135) 50.8 (197,683) 38.1 (338) 
 Former 22.7 (60,121) 20.1 (75) 37.0 (46,030) 37.7 (194) 27.3 (106,151) 30.3 (269) 
 Current 18.6 (49,258) 25.5 (95) 29.0 (36,128) 36.1 (186) 21.9 (85,386) 31.6 (281) 
Physical activity, % (n      
 Inactive 22.3 (58,926) 26.5 (99) 17.6 (21,923) 20.6 (106) 20.8 (80,849) 23.1 (205) 
 Moderately inactive 36.3 (96,167) 37.5 (140) 31.8 (39,601) 37.9 (195) 34.9 (135,768) 37.7 (335) 
 Moderately active 24.7 (65,315) 17.4 (65) 24.8 (30,892) 22.7 (117) 24.7 (96,207) 20.5 (182) 
 Active 16.7 (44,244) 18.5 (69) 25.8 (32,152) 18.8 (97) 19.6 (76,396) 18.7 (166) 
Hypertensionb, % (n17.8 (47,199) 29.8 (111) 20.2 (25,108) 30.5 (157) 18.6 (72,307) 30.2 (268) 
Diabetesb, % (n2.1 (5,577) 3.8 (14) 3.4 (4,176) 4.7 (24) 2.5 (9,753) 4.3 (38) 
BMI (kg/m2), median (IQR) 24.0 (21.8–27.1) 25.6 (23.2–28.9) 26.1 (24.0–28.5) 27.1 (24.8–29.7) 24.8 (22.4–27.7) 26.5 (24.2–29.5) 
Alcohol intake (g/day), median (IQR) 4.2 (0.6–12.1) 1.8 (0.2–8.7) 12.9 (4.2–30.2) 13.6 (4.4–31.7) 6.4 (1.1–16.7) 7.5 (1.0–22.4) 
Energy intake (kcal/day), median (IQR) 1,907.7 (1,580.6–2,293.2) 1,806.2 (1,496.6–2,207.5) 2,356.8 (1,953.3–2,818.4) 2,341.6 (1,986.0–2,791.0) 2,038.3 (1,669.2–2,478.1) 2,119.5 (1,724.6–2,578.0) 
Fruit and vegetable juice intake (g/day), median (IQR)c 47.1 (10.7–120.0) 35.7 (8.3–120.0) 32.1 (8.3–101.9) 28.6 (8.2–103.4) 42.9 (9.0–120.0) 33.3 (8.3–120.0) 
Total soft drink intake (g/day), median (IQR)c 41.9 (13.4–138.5) 56.0 (14.8–175.5) 62.6 (19.7–194.9) 71.4 (16.4–157.1) 48.6 (16.4–157.1) 63.4 (16.4–171.4) 
Sugar-sweetened soft drink intake (g/day), median (IQR)c,d 28.6 (4.8–107.1) 31.5 (12.2–117.0) 45.5 (14.0–153.5) 46.3 (7.3–127.5) 32.1 (6.6–113.2) 35.4 (8.6–121.4) 
Artificially sweetened soft drink intake (g/day), median (IQR)c,d 14.3 (2.0–85.7) 21.8 (6.6–103.8) 16.4 (3.3–85.7) 16.4 (3.3–89.0) 14.3 (2.0–85.7) 19.7 (6.5–92.3) 

Abbreviations: BMI, body mass index; IQR, interquartile range; n, number of participants; RCC, renal cell carcinoma.

aGreece was excluded and Norway was not included in analyses because data on physical activity index were not available.

bSelf-reported at recruitment.

cMedian (IQR) among consumers. Overall ranges of intake were 0–4,000 g/day for juices, 0–4,202 g/day for total soft drinks, 0–4,202 g/day for sugar-sweetened soft drinks, and 0–3,389 g/day for artificially sweetened soft drinks.

dInformation on types of soft drinks was not available in Umeå (Sweden) and centers in Italy and Spain.

Intakes of juices and total, sugar-sweetened, or artificially sweetened soft drinks were not associated with RCC incidence (Table 2). Total and artificially-sweetened soft drinks were positively associated with RCC mortality in models unadjusted for BMI and energy intake, but not after adjustment. Juice consumption was positively associated with RCC mortality in women, even after adjustment for BMI and energy intake (HR per 100 g/day increment = 1.17; 95% CI, 1.05–1.29; Pinteraction by sex = 0.02). There was no strong evidence of nonlinearity of associations (Supplementary Figs. S1 and S2), and in fully adjusted models HRs (95% CIs) for 400 g/day compared with no intake of juices, total soft drinks, sugar-sweetened soft drinks, and artificially sweetened soft drinks were 1.06 (0.85–1.34), 1.13 (0.93–1.38), 1.00 (0.77–1.29), and 1.21 (0.91–1.61), respectively, for RCC incidence, and 1.25 (0.87–1.79), 1.01 (0.75–1.37), 0.86 (0.59–1.27), and 1.38 (0.93–2.05) for RCC mortality (Supplementary Table S1). Results were similar in sensitivity analyses (Supplementary Tables S2–S4).

Table 2.

RCC incidence and mortality in relation to a 100 g/day increment in the consumption of juices, total soft drinks, sugar-sweetened soft drinks, and artificially sweetened soft drinks in the EPIC study.

RCC incidenceaRCC mortalityb
Adjusted modelcAdditionally adjusted for BMI and energy intakedAdjusted modelcAdditionally adjusted for BMI and energy intaked
ParticipantsCasesHR (95% CI) per 100 g/dayPPinteractionHR (95% CI) per 100 g/dayPPinteractionDeathsHR (95% CI) per 100 g/dayPPinteractionHR (95% CI) per 100 g/dayPPinteraction
Juice intake                
Overall 389,220 888 1.03 (0.97–1.09) 0.31  1.03 (0.97–1.09) 0.39  356 1.08 (0.99–1.17) 0.11  1.06 (0.97–1.16) 0.20  
 Women 264,652 373 1.02 (0.93–1.12) 0.71 0.78 1.02 (0.92–1.12) 0.74 0.82 158 1.18 (1.07–1.30) 0.001 0.02 1.17 (1.05–1.29) 0.003 0.02 
 Men 124,568 515 1.04 (0.97–1.11) 0.32  1.03 (0.96–1.10) 0.40  198 0.94 (0.80–1.11) 0.50  0.93 (0.79–1.09) 0.38  
Total soft drink intake              
Overall 389,220 888 1.02 (0.99–1.06) 0.21  1.01 (0.98–1.05) 0.46  356 1.05 (1.00–1.10) 0.06  1.03 (0.98–1.09) 0.28  
 Women 264,652 373 1.05 (0.99–1.11) 0.08 0.25 1.04 (0.98–1.10) 0.19 0.32 158 1.09 (1.02–1.17) 0.01 0.16 1.07 (1.00–1.15) 0.07 0.19 
 Men 124,568 515 1.01 (0.96–1.06) 0.76  1.00 (0.95–1.05) 0.99  198 1.02 (0.95–1.09) 0.66  1.00 (0.93–1.08) 0.97  
Sugar-sweetened soft drink intakee             
Overall 281,483 589 1.00 (0.95–1.06) 0.95  0.99 (0.94–1.05) 0.84  265 0.99 (0.91–1.09) 0.90  0.97 (0.89–1.07) 0.56  
 Women 197,502 242 1.04 (0.95–1.14) 0.42 0.38 1.03 (0.94–1.13) 0.53 0.38 123 1.07 (0.95–1.20) 0.27 0.16 1.05 (0.93–1.18) 0.44 0.15 
 Men 83,981 347 0.98 (0.92–1.06) 0.67  0.98 (0.91–1.05) 0.53  142 0.94 (0.83–1.07) 0.35  0.92 (0.81–1.05) 0.21  
Artificially sweetened soft drink intakee             
Overall 281,483 589 1.03 (0.97–1.09) 0.32  1.02 (0.96–1.08) 0.61  265 1.08 (1.01–1.16) 0.03  1.06 (0.99–1.14) 0.11  
 Women 197,502 242 1.06 (0.98–1.15) 0.13 0.32 1.05 (0.96–1.14) 0.28 0.37 123 1.10 (1.01–1.21) 0.03 0.52 1.08 (0.98–1.19) 0.11 0.57 
 Men 83,981 347 1.00 (0.93–1.09) 0.93  0.99 (0.91–1.08) 0.85  142 1.06 (0.95–1.17) 0.30  1.04 (0.93–1.15) 0.49  
RCC incidenceaRCC mortalityb
Adjusted modelcAdditionally adjusted for BMI and energy intakedAdjusted modelcAdditionally adjusted for BMI and energy intaked
ParticipantsCasesHR (95% CI) per 100 g/dayPPinteractionHR (95% CI) per 100 g/dayPPinteractionDeathsHR (95% CI) per 100 g/dayPPinteractionHR (95% CI) per 100 g/dayPPinteraction
Juice intake                
Overall 389,220 888 1.03 (0.97–1.09) 0.31  1.03 (0.97–1.09) 0.39  356 1.08 (0.99–1.17) 0.11  1.06 (0.97–1.16) 0.20  
 Women 264,652 373 1.02 (0.93–1.12) 0.71 0.78 1.02 (0.92–1.12) 0.74 0.82 158 1.18 (1.07–1.30) 0.001 0.02 1.17 (1.05–1.29) 0.003 0.02 
 Men 124,568 515 1.04 (0.97–1.11) 0.32  1.03 (0.96–1.10) 0.40  198 0.94 (0.80–1.11) 0.50  0.93 (0.79–1.09) 0.38  
Total soft drink intake              
Overall 389,220 888 1.02 (0.99–1.06) 0.21  1.01 (0.98–1.05) 0.46  356 1.05 (1.00–1.10) 0.06  1.03 (0.98–1.09) 0.28  
 Women 264,652 373 1.05 (0.99–1.11) 0.08 0.25 1.04 (0.98–1.10) 0.19 0.32 158 1.09 (1.02–1.17) 0.01 0.16 1.07 (1.00–1.15) 0.07 0.19 
 Men 124,568 515 1.01 (0.96–1.06) 0.76  1.00 (0.95–1.05) 0.99  198 1.02 (0.95–1.09) 0.66  1.00 (0.93–1.08) 0.97  
Sugar-sweetened soft drink intakee             
Overall 281,483 589 1.00 (0.95–1.06) 0.95  0.99 (0.94–1.05) 0.84  265 0.99 (0.91–1.09) 0.90  0.97 (0.89–1.07) 0.56  
 Women 197,502 242 1.04 (0.95–1.14) 0.42 0.38 1.03 (0.94–1.13) 0.53 0.38 123 1.07 (0.95–1.20) 0.27 0.16 1.05 (0.93–1.18) 0.44 0.15 
 Men 83,981 347 0.98 (0.92–1.06) 0.67  0.98 (0.91–1.05) 0.53  142 0.94 (0.83–1.07) 0.35  0.92 (0.81–1.05) 0.21  
Artificially sweetened soft drink intakee             
Overall 281,483 589 1.03 (0.97–1.09) 0.32  1.02 (0.96–1.08) 0.61  265 1.08 (1.01–1.16) 0.03  1.06 (0.99–1.14) 0.11  
 Women 197,502 242 1.06 (0.98–1.15) 0.13 0.32 1.05 (0.96–1.14) 0.28 0.37 123 1.10 (1.01–1.21) 0.03 0.52 1.08 (0.98–1.19) 0.11 0.57 
 Men 83,981 347 1.00 (0.93–1.09) 0.93  0.99 (0.91–1.08) 0.85  142 1.06 (0.95–1.17) 0.30  1.04 (0.93–1.15) 0.49  

Abbreviations: BMI, body mass index; CI, confidence interval; HR, hazard ratio; RCC, renal cell carcinoma.

aIncident RCC was defined as histologically confirmed first invasive RCC diagnosis coded according to the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) C64.

bRCC deaths included all deaths in which the underlying cause of death was ICD-10 C64.

cMultivariable Cox regression models were stratified by sex and country and adjusted for age at recruitment (continuous, years), educational attainment (none/primary school, technical or professional school, secondary school, longer education including university), smoking status (never, former, current), alcohol consumption (continuous, g/day), physical activity (inactive, moderately inactive, moderately active, active), juice intake (continuous, g/day; for soft drink analyses), and total soft drink intake (continuous, g/day; for juice analyses). Sugar-sweetened and artificially sweetened soft drinks were mutually adjusted.

dModels were as described for the adjusted modelc and additionally adjusted for body mass index (continuous, kg/m2) and total energy intake (continuous, kcal/day).

eUmeå (Sweden) and centers in Italy and Spain were not included in these analyses as information on types of soft drinks was not available.

In this prospective European study, intakes of juices or soft drinks were not associated with RCC incidence or mortality independent of obesity.

The absence of clear associations between consumption of juices and RCC risk in EPIC is consistent with other prospective studies (4, 8). The higher RCC mortality associated with higher juice intake in women is not interpretable and could be a chance finding.

The lack of association between soft drink consumption and RCC mortality aligns with previous EPIC findings showing no association between soft drink consumption and overall cancer mortality, despite a strong association with all-cause mortality (9). A meta-analysis did not identify associations between soft drink consumption and several cancer types, including kidney cancer (5), and other prospective studies investigating RCC/kidney cancer similarly have not found clear associations (4, 6).

Strengths of this study include its prospective design in European populations with different food and beverage habits, long follow-up time, many RCC cases, and detailed personal and lifestyle information which enabled control for multiple covariates. Limitations include the single assessment of diet at baseline, incomplete data on soft drink types in some countries, and inability to distinguish between juice types (fruit/vegetable/nectars/added sugars). Because few participants had very high intakes of these beverages, we cannot rule out the possibility that higher consumption levels might be associated with RCC.

In conclusion, in this large European prospective cohort study, consumption of soft drinks or juices was not associated with RCC incidence or mortality independent of obesity.

B. Ljungberg reports personal fees from Novartis, BMS, Janssen, Ipsen, and MSD, and nonfinancial support from Jensen and Astellas outside the submitted work. D.C. Muller reports grants from Cancer Research UK during the conduct of the study and grants from U.S. NIH/NCI outside the submitted work. No disclosures were reported by the other authors.

Where authors are identified as personnel of the International Agency for Research on Cancer/World Health Organization, the authors alone are responsible for the views expressed in this article and they do not necessarily represent the decisions, policy, or views of the International Agency for Research on Cancer/World Health Organization.

A.K. Heath: Conceptualization, formal analysis, supervision, investigation, visualization, methodology, writing–original draft, writing–review and editing. J.L. Clasen: Investigation, visualization, methodology, writing–review and editing. N.P. Jayanth: Formal analysis, investigation, writing–review and editing. M. Jenab: Writing–review and editing. A. Tjønneland: Resources, data curation, writing–review and editing. K.E.N. Petersen: Writing–review and editing. K. Overvad: Resources, data curation, writing–review and editing. B. Srour: Writing–review and editing. V. Katzke: Writing–review and editing. M.M. Bergmann: Writing–review and editing. M.B. Schulze: Resources, data curation, writing–review and editing. G. Masala: Writing–review and editing. V. Krogh: Resources, data curation, writing–review and editing. R. Tumino: Resources, data curation, writing–review and editing. A. Catalano: Writing–review and editing. F. Pasanisi: Writing–review and editing. M. Brustad: Writing–review and editing. K.S. Olsen: Writing–review and editing. G. Skeie: Resources, data curation, writing–review and editing. L. Luján-Barroso: Writing–review and editing. M. Rodríguez-Barranco: Writing–review and editing. P. Amiano: Resources, data curation, writing–review and editing. C. Santiuste: Writing–review and editing. A. Barricarte Gurrea: Resources, data curation, writing–review and editing. H. Axelson: Writing–review and editing. S. Ramne: Writing–review and editing. B. Ljungberg: Writing–review and editing. E.L. Watts: Writing–review and editing. I. Huybrechts: Data curation, writing–review and editing. E. Weiderpass: Resources, writing–review and editing. E. Riboli: Resources, supervision, funding acquisition, project administration, writing–review and editing. D.C. Muller: Conceptualization, supervision, investigation, visualization, methodology, writing–review and editing.

The authors thank all participants in the EPIC cohort for their invaluable contribution to the study. We acknowledge the National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands, for their contribution and ongoing support to the EPIC Study and acknowledge the use of data from the EPIC-France cohort, PIs Gianluca Severi and Marie-Christine Boutron-Ruault; EPIC-Utrecht cohort, PI Roel Vermeulen; EPIC-Asturias cohort, PI José Ramón Quirós; and EPIC-Norfolk cohort, PI Nick Wareham. Cancer Research UK Population Research Fellowship (D.C. Muller); Imperial College London President's PhD Scholarship (J.L. Clasen); Nuffield Department of Population Health Early Career Research Fellowship (E.L. Watts). The coordination of EPIC is financially supported by International Agency for Research on Cancer (IARC) and also by the Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, which has additional infrastructure support provided by the NIHR Imperial Biomedical Research Centre (BRC). The national cohorts are supported by Danish Cancer Society (Denmark); Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l'Education Nationale, Institut National de la Santé et de la Recherche Médicale (INSERM) (France); German Cancer Aid, German Cancer Research Center (DKFZ), German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), Federal Ministry of Education and Research (BMBF) (Germany); Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy, Compagnia di SanPaolo and National Research Council (Italy); Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands (the Netherlands); Health Research Fund (FIS) - Instituto de Salud Carlos III (ISCIII), Regional Governments of Andalucía, Asturias, Basque Country, Murcia and Navarra, and the Catalan Institute of Oncology - ICO (Spain); Swedish Cancer Society, Swedish Research Council and County Councils of Skåne and Västerbotten (Sweden); and Cancer Research UK (14136 to EPIC-Norfolk; C8221/A29017 to EPIC-Oxford), Medical Research Council (1000143 to EPIC-Norfolk; MR/M012190/1 to EPIC-Oxford; United Kingdom).

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

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