IJC International Journal of Cancer
Alcohol consumption and the risk of renal cancers in the European prospective investigation into cancer and nutrition (EPIC) Magdalena B. Wozniak1, Paul Brennan1, Darren R. Brenner1,2, Kim Overvad3, Anja Olsen4, Anne Tjønneland4, €hn7, Marie-Christine Boutron-Ruault5,6, Franc¸oise Clavel-Chapelon5,6, Guy Fagherazzi5,6, Verena Katzke7, Tilman Ku 8 8 8 9,10 9,10,11 Heiner Boeing , Manuela M. Bergmann , Annika Steffen , Androniki Naska , Antonia Trichopoulou , Dimitrios Trichopoulos10,11,12†, Calogero Saieva13, Sara Grioni14, Salvatore Panico15, Rosario Tumino16, Paolo Vineis17,18, H. B(as) Bueno-de-Mesquita19,20,21,22, Petra H. Peeters23,24, Anette Hjarta˚ker25, Elisabete Weiderpass26,27,28,29, n Alonso de la Torre35, Larraitz Arriola30, Esther Molina-Montes31,32, Eric J. Duell33, Carmen Santiuste34, Ramo 36,37 38,39 1,39 €rje Ljungberg39, Nick Wareham40, Aurelio Barricarte Gurrea , Tanja Stocks , Mattias Johansson , Bo 41 42 17 17 Kay-Tee Khaw , Ruth C. Travis , Amanda J. Cross , Neil Murphy , Elio Riboli17 and Ghislaine Scelo1 1
Genetic Epidemiology Group, International Agency for Research on Cancer (IARC), Lyon, France Department of Population Health Research, Cancer Control Alberta, Alberta Health Services, Calgary, AB, Canada 3 Department of Public Health, Section for Epidemiology, Aarhus University, Aarhus, Denmark 4 Department of Diet, Genes and Environment, Danish Cancer Society Research Center, Copenhagen, Denmark 5 Centre for Research in Epidemiology and Population Health (CESP), INSERM, Villejuif, France 6 Institut Gustave-Roussy (IGR), Universite Paris Sud, INSERM, Villejuif, France 7 Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany 8 €cke, Nuthetal, Germany Department of Epidemiology, German Institute of Human Nutrition (DIfE) Potsdam-Rehbru 9 Department of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School, Athens, Greece 10 Hellenic Health Foundation, Athens, Greece 11 Bureau of Epidemiologic Research, Academy of Athens, Greece 12 Department of Epidemiology, Harvard School of Public Health, Boston, MA 13 Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute (ISPO), Florence, Italy 14 Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale Dei Tumori, Milan, Italy 15 Department of Clinical and Experimental Medicine, Federico II University, Naples, Italy 16 Cancer Registry and Histopathology Unit, "Civic - M.P. Arezzo" Hospital, ASP Ragusa, Italy 17 Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, United Kingdom 18 HuGeF Foundation, Torino, Italy 19 Department for Determinants of Chronic Diseases (DCD), National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands
Key words: kidney cancer, renal cell carcinoma, risk factors, alcohol consumption, EPIC, cohort study Additional Supporting Information may be found in the online version of this article. † Deceased. This work was supported by the US National Cancer Institute (U01-CA155309). The coordination of EPIC is financially supported by the European Commission (DG-SANCO) and the International Agency for Research on Cancer. The national cohorts are supported by: Danish Cancer Society (Denmark); Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Generale de l’Education Nationale, Institut National de la Sante et de la Recherche Medicale (INSERM) (France); Deutsche Krebshilfe, Deutsches Krebsforschungszentrum, Federal Ministry of Education and Research (Germany); Stavros Niarchos Foundation, Hellenic Health Foundation (Greece); Italian Association for Research on Cancer (AIRC), National Research Council, HuGeF Foundation, Compagnia di San Paolo, Sicily Regional Government, AIRE ONLUS Ragusa, AVIS Ragusa (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 Funds (WCRF), Statistics Netherlands (The Netherlands); European Research Council (ERC-2009-AdG232997), Nordforsk (Nordic Center of Excellence programme on Food, Nutrition and Health), Norwegian Research Council, Norwegian Cancer Society, University of Tromso (Norway); Health Research Funds (FIS), Regional Governments of Andalusia, Asturias, Basque Country, Murcia (No. 6236), and Navarra, Instituto de Salud Carlos III (RETIC RD06/0020) (Spain); Swedish Cancer Society, Swedish Scientific Council, Regional Government of Skåne V€asterbotten (Sweden); Cancer Research UK, Medical Research Council (United Kingdom). DOI: 10.1002/ijc.29559 History: Received 6 Nov 2014; Accepted 16 Mar 2015; Online 9 Apr 2015 Correspondence to: Ghislaine Scelo, Genetic Epidemiology Group (GEP), International Agency for Research on Cancer (WHO-IARC), 150 Cours Albert Thomas, 69372 Lyon Cedex 08, France, Tel.: 1[33(0)472738173], Fax: 1[33(0)472738342], E-mail: [email protected]
C 2015 UICC Int. J. Cancer: 137, 1953–1966 (2015) V
Epidemiology
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Alcohol consumption and the risk of renal cancers
What’s new? Previous studies have indicated that environmental or lifestyle factors may be involved in the etiology of renal cancer, and that moderate alcohol consumption may reduce the risk of this type of cancer. In this very large European study (nearly 500,000 subjects), the authors found that, indeed, total alcohol consumption was inversely associated with renal cancer overall (for all subsites combined), and also with cancers of the renal parenchyma.
20
Department of Gastroenterology and Hepatology, University Medical Centre, Utrecht, The Netherlands Department of Epidemiology and Biostatistics, the School of Public Health, Imperial College London, United Kingdom 22 Department of Social & Preventive Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia 23 Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center, Utrecht, The Netherlands 24 MRC-PHE, Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, United Kingdom 25 Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway 26 Department of Community Medicine, Faculty of Health Sciences, University of Tromsø, The Arctic University of Norway, Tromsø, Norway 27 Cancer Registry of Norway, Oslo, Norway 28 Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden 29 Department of Genetic Epidemiology, Folkh€alsan Research Center, Helsinki, Finland 30 blica (CIBERESP), San Sebastian, Public Health Division of Gipuzkoa, Instituto BIO-Donostia, Basque Government, CIBER De Epidemiologıa Y Salud Pu Spain 31 n Biosanitaria, Universidad De Granada, Granada, Spain blica, Instituto De Investigacio Escuela Andaluza De Salud Pu 32 blica (CIBERESP), Granada, Spain CIBER De Epidemiologıa Y Salud Pu 33 Unit of Nutrition, Environment and Cancer, Cancer Epidemiology Research Program, Catalan Institute of Oncology (ICO), L’hospitalet De Llobregat, Barcelona, Spain 34 Department of Epidemiology, Murcia Regional Health Council, IMIB-Arrixaca, Murcia, Spain 35 Public Health Directorate, Asturias, Spain 36 Navarre Public Health Institute, Pamplona, Spain 37 blica (CIBERESP), Madrid, Spain CIBER De Epidemiologıa Y Salud Pu 38 €, Sweden Department of Clinical Sciences, Lund University, Malmo 39 Department of Surgical and Perioperative Sciences, Urology and Andrology, Umea˚ University, Umea˚, Sweden 40 MRC Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom 41 School of Clinical Medicine, University of Cambridge, Cambridge, United Kingdom 42 Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom
Epidemiology
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Epidemiologic studies have reported that moderate alcohol consumption is inversely associated with the risk of renal cancer. However, there is no information available on the associations in renal cancer subsites. From 1992 through to 2010, 477,325 men and women in the European Prospective Investigation into Cancer and Nutrition cohort were followed for incident renal cancers (n 5 931). Baseline and lifetime alcohol consumption was assessed by country-specific, validated dietary questionnaires. Information on past alcohol consumption was collected by lifestyle questionnaires. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated from Cox proportional hazard models. In multivariate analysis, total alcohol consumption at baseline was inversely associated with renal cancer; the HR and 95% CI for the increasing categories of total alcohol consumption at recruitment versus the light drinkers category were 0.78 (0.62–0.99), 0.82 (0.64–1.04), 0.70 (0.55–0.90), 0.91 (0.63–1.30), respectively, (ptrend 5 0.001). A similar relationship was observed for average lifetime alcohol consumption and for all renal cancer subsites combined or for renal parenchyma subsite. The trend was not observed in hypertensive individuals and not significant in smokers. In conclusion, moderate alcohol consumption was associated with a decreased risk of renal cancer.
Renal cancers consist of malignant tumors of renal parenchyma and renal pelvis. Adenocarcinoma of renal parenchyma [referred to as renal cell carcinoma (RCC)] accounts for over 90% of renal cancers while nearly all cancers arising in renal pelvis are of the transitional cell type and comprise 0–6 (men) >0–3 (women)
1.6
18.1
2.5
18.3
25.6
54.1
24.5 (4.1)
65.0 (11.0)
163.0 (6.5)
6.9 (2.6)
50.4 (9.9)
100,238 (29.9)
0.93 (0.06)
100.5 (6.6)
93.9 (10.0)
3.2
22.0
1.6
24.9
35.8
37.8
26.2 (3.6)
80.7 (11.8)
175.4 (7.3)
8.9 (1.7)
52.0 (10.8)
23,939 (16.8)
>6–12 (men) >3–12 (women)
1.5
17.6
2.1
20.5
26.4
51.0
24.2 (3.8)
64.1 (10.3)
162.6 (6.5)
16.7 (3.6)
51.0 (9.6)
44,167 (13.2)
0.94 (0.06)
100.6 (6.6)
94.2 (9.8)
3.0
22.3
1.2
27.9
39.6
31.4
26.4 (3.5)
81.0 (11.6)
175.1 (7.2)
17.3 (3.5)
52.6 (9.7)
29,266 (20.6)
>12–24
1.6
17.6
2.2
28.1
28.4
41.4
24.2 (3.8)
64.4 (10.5)
163.0 (6.3)
34.8 (8.8)
51.7 (8.5)
26,261 (7.8)
0.94 (0.06)
101.0 (6.7)
95.1 (9.7)
3.1
22.9
1.0
34.7
39.5
24.9
26.7 (3.5)
81.3 (11.6)
174.5 (7.3)
37.8 (9.8)
52.4 (8.8)
34,576 (24.3)
>24–60
Baseline alcohol consumption (g/d)
2.5
21.6
3.2
39.9
24.5
32.5
24.6 (4.0)
65.8 (11.4)
163.6 (6.1)
76.2 (17.3)
51.8 (8.1)
2,176 (0.7)
0.96 (0.06)
101.9 (7.4)
97.8 (10.5)
4.1
25.4
0.5
49.2
33.9
16.4
27.4 (3.9)
83.2 (12.7)
174.2 (7.2)
82.3 (25.4)
53.0 (7.6)
9,363 (6.6)
>60
Table 2. Baseline characteristics of study participants by total alcohol consumption at recruitment, the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, 1992– 2010
Epidemiology
1958 Alcohol consumption and the risk of renal cancers
C 2015 UICC Int. J. Cancer: 137, 1953–1966 (2015) V
11,539 (2.4) Continuous variables are presented as means and standard deviations (SD), categorical variables are presented as percentages. Unknown values were excluded from the calculations. Percent of missing data were for hypertension, 13.2%; diabetes, 3.5%; waist circumference, 22.4%; hip circumference, 22.4%; waist-hip ratio, 22.4%. 2
931 All Participants (n, %)
476,394
64,134 (13.4)
143,205 (30.0)
124,177 (26.0)
73,433 (15.4)
60,837 (12.8) 1
0.82 (0.08)
100.3 (8.7) 99.7 (8.1)
0.79 (0.07) 0.79 (0.07)
99.5 (8.1) 100.1 (8.7)
0.78 (0.07) 0.79 (0.07)
101.4 (9.6) 104.1 (10.3)
0.81 (0.07) 0.79 (0.07) Waist-hip-ratio2
101.0 (9.3) 102.8 (9.7)
0.82 (0.08)
Hip circumference2 (cm)
82.0 (11.5)
>60 >24–60
79.2 (10.3) 78.3 (10.1) 78.6 (10.7) 80.1 (11.7)
>12–24 Nondrinkers
84.9 (12.4) 80.1 (11.4)
Noncases Cases
84.0 (12.2) Waist circumference2 (cm)
Baseline alcohol consumption (g/d)
>6–12 (men) >3–12 (women) >0–6 (men) >0–3 (women)
Characteristics1
Table 2. Baseline characteristics of study participants by total alcohol consumption at recruitment, the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, 1992– 2010 (Continued)
C 2015 UICC Int. J. Cancer: 137, 1953–1966 (2015) V
hypertension and diabetes showing 31.2 and 7.2% in men and 25.9 and 4.6% in women, respectively. The nonlinear regression analyses for baseline and lifetime alcohol consumption and renal cancer risk for men and women combined are presented in Figures 1 and 2. These nonparametric regression analyses showed evidence of nonlinearity in the association between alcohol consumption and renal cancer risk in the multivariable model for both baseline (p values 5 0.113) and lifetime alcohol consumption (p-value 5 0.035). For both baseline and lifetime alcohol consumption, a linear inverse association was observed in participants with alcohol consumption lower than 10 g/day, this relationship became flat above 10 g/ day. Overall, total baseline and lifetime alcohol consumption were inversely associated with risk of renal cancer (Table 3). In the multivariate model, decreased risks (ptrend 5 0.001) were observed between baseline alcohol consumption and renal cancers combined, compared with light drinkers. This inverse trend remained significant when estimated for drinkers only (ptrend 5 0.047). Similar HRs were observed when diabetes and physical activity were added as covariates to the multivariable model (data not shown). The inverse association for baseline alcohol consumption was mostly driven by the association in renal parenchyma (ptrend 5 0.026) where lower HRs were observed than in renal pelvis. The competing risk analysis provided very similar HRs (Supporting Information Table S1). In addition, similar trends for inverse association have been found in different geographical regions (Supporting Information Table S2). We further assessed associations for specific alcoholic beverages, alcohol consumption from beer, wine, liquor and spirits for men and women combined (Table 3). Among all cohort participants 18% of men and 46% of women were nonbeer drinkers, 13% of men and 20% of women were non-wine drinkers and 28% of men and 56% of women were not drinking spirits and liquor beverages. On average, men had a higher use of alcohol from each beverage for both consumption at recruitment and lifetime. The median consumption for beverages (in grams of alcohol from beverage per day) at recruitment was: beer 4.8 g/d for men and 0.6 g/d for women, wine 5.1 g/d for men and 3.7 g/d for women, liquor and spirits 1.2 g/d for men and 0.4 g/d for women. One type of alcoholic beverage alone was not associated with the risk of all renal cancer subsites combined, when adjusted for other types of alcoholic beverages. Looking at these associations separately by sex did not show strong associations (Supporting Information Tables S3 and S4). There was however a significant inverse association with lifetime consumption of alcohol from liquor and spirits among men (ptrend 5 0.030). A significant inverse association was observed in wine only drinkers, particularly in women where a HR of 0.51 (95% CI 0.31–0.84) was observed
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Alcohol consumption and the risk of renal cancers
Figure 1. HRs (solid line) and 95% CIs (gray shade) for baseline alcohol consumption and renal cancer risk evaluated using restricted cubic spline regression (4 knots) for men and women combined in the EPIC cohort. Participants with extreme alcohol consumption of [mt]60 g/day and nondrinkers were excluded. The model was adjusted for age at recruitment, hypertension, sex, BMI, smoking status, waist-to-hip ratio and stratified by center. European Prospective Investigation into Cancer and Nutrition (EPIC), 1992–2010. [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]
Figure 2. HRs (solid line) and 95% CIs (gray shade) for lifetime alcohol consumption and renal cancer risk evaluated using restricted cubic spline regression (4 knots) for men and women combined in the EPIC cohort. Participants with extreme alcohol consumption of more than 60 g/day and nondrinkers were excluded. The model was adjusted for age at recruitment, hypertension, sex, BMI, smoking status, waist-to-hip ratio and stratified by center. European Prospective Investigation into Cancer and Nutrition (EPIC), 1992–2010. [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]
(Supporting Information Table S5). Beer only drinkers also showed an inverse association with renal cancer risk, although not significantly. Table 4 presents the HRs for renal cancer and alcohol consumption at baseline stratified by sex, history of hypertension, smoking status, diabetes and BMI. We found an inverse association between total alcohol consumption and renal cancer in both sexes with stronger effects in women (men: ptrend 5 0.057; women: ptrend 5 0.003). Interestingly, a lower risk of renal cancer was found for participants who declared no history of hypertension. These results were of similar magnitude for lifetime consumption (Supporting Information Table S6). In addition, the associations between baseline and average lifetime alcohol consumption were not modified by sex, hypertension, smoking status, diabetes and BMI as evaluated by likelihood ratio test based on models with and without interaction term. Nonsignificant interactions were observed for alcohol consumption and all variables (all pinteraction > 0.05).
time. We found that alcohol consumption was inversely associated with the risk of renal cancer in men and women. The study supports previous evidence of an inverse association between alcohol consumption and the risk of renal cancers. In addition, this study evaluated alcohol consumption in different renal cancer subsites including renal parenchyma and renal pelvis showing significant inverse associations of moderate alcohol consumption and cancers of renal parenchyma. Interestingly, our data also revealed that individuals with self-reported hypertension did not present lower risk of renal cancers combined in relation to alcohol consumption. Moderate alcohol consumption was inversely associated with renal cancer in our study and supports previous reports of case–control and prospective studies that have shown an inverse association between alcohol consumption and risk of RCC.15–25,39,40 We did not find any clear dose response relationship for the main analyses. The inverse association was observed for all renal cancer subsites combined and subsite of renal parenchyma. However, other cohort11–14,41 and case-control studies8–10 have reported no association. These dissimilarities could be due to different methodologies used to study alcohol consumption and renal cancer risk, quality of data, sample size and varying categories of alcohol consumption.
Discussion In this large prospective European cohort study, we assessed two measures of alcohol consumption. These included alcohol consumption at recruitment, which evaluates recent consumption only as well as alcohol consumption over life-
C 2015 UICC Int. J. Cancer: 137, 1953–1966 (2015) V
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Wozniak et al.
Table 3. Multivariable-adjusted HR and 95% CIs for renal cancer in relation to baseline and lifetime alcohol consumption in the European Prospective Investigation into Cancer and Nutrition (EPIC) study, 1992–2010. Total renal cancer Alcohol consumption
Cases1
Renal parenchyma
HR (95% CI)2
Cases
HR (95% CI)2
Renal pelvis Cases
HR (95% CI)2
Baseline (g/d) Nondrinkers
83
1.21 (0.91–1.59)
56
11
2.67 (1.05–6.83)
>0–6 (M)/> 0–3 (W)
170
Reference
131
Reference
1 (0.72–1.39)
10
Reference
>6 – 12 (M)/> 3 – 12 (W)
120
0.78 (0.62–0.99)
92
0.80 (0.61–1.04)
11
1.00 (0.42–2.37)
> 12 – 24
118
0.82 (0.64–1.04)
80
0.72 (0.54–0.96)
15
1.47 (0.65–3.33)
>24 – 60
116
0.70 (0.55–0.90)
86
0.67 (0.50–0.89)
10
0.88 (0.36–2.19)
>60
41
0.91 (0.63–1.30)
34
0.98 (0.66–1.46)
3
0.92 (0.24–3.53)
P-trend3
0.001
0.026
0.112
Average lifetime (g/d) Nondrinkers
42
1.44 (0.99–2.08)
27
1.19 (0.76–1.86)
5
3.04 (0.88–10.55)
Former
31
1.05 (0.70–1.57)
21
0.90 (0.56–1.46)
4
2.00 (0.56–7.09)
>0 – 6 (M)/> 0 – 3 (W)
136
Reference
102
Reference
8
Reference
>6 – 12 (M)/> 3 – 12 (W)
125
0.73 (0.57–0.93)
85
0.66 (0.49–0.88)
21
1.59 (0.70–3.61)
>12 – 24
125
0.86 (0.66–1.11)
92
0.84 (0.62–1.13)
10
0.84 (0.32–2.19)
>24 – 60
104
0.76 (0.57–1.00)
78
0.73 (0.53–1.02)
7
0.67 (0.23–1.96)
>60
32
0.94 (0.61–1.44)
28
1.04 (0.65–1.67)
1
0.43 (0.05–3.83)
P-trend3
0.007
0.138
0.018
4
Baseline alcohol consumption by types of alcoholic beverage Beer (g/d) Nondrinkers
211
1.23 (0.94–1.60)
156
1.16 (0.86–1.57)
18
1.70 (0.59–4.95)
Q1 (> 0–0.43)
98
Reference
80
Reference
5
Reference
Q2 (> 0.43–1.37)
68
1.12 (0.81–1.54)
55
1.15 (0.80–1.65)
7
1.98 (0.60–6.49)
Q3 (> 1.37–5.27)
90
0.99 (0.73–1.35)
57
0.73 (0.51–1.05)
8
1.86 (0.57–6.02)
Q4 (> 5.27)
181
0.96 (0.72–1.29)
131
0.83 (0.59–1.15)
22
2.19 (0.73–6.59)
P-trend3
0.093
0.012
0.418
Nondrinkers
92
1.13 (0.84–1.52)
64
0.98 (0.69–1.38)
10
1.89 (0.68–5.24)
Q1 (> 0–0. 98)
125
Reference
93
Reference
8
Reference
Q2 (> 0. 98–4.42)
156
1.09 (0.86–1.39)
118
1.08 (0.82–1.42)
15
1.52 (0.64–3.62)
Q3 (> 4.42–9.76)
127
0.96 (0.75–1.24)
88
0.90 (0.67–1.22)
15
1.36 (0.56–3.29)
Q4 (> 9.76)
148
0.89 (0.68-1.16)
116
0.89 (0.66-1.22)
12
1.01 (0.39–2.64)
3
P-trend
0.119
0.416
0.420
Liquor and spirits (g/d) Nondrinkers
228
0.94 (0.70–1.26)
168
0.99 (0.70–1.40)
22
2.08 (0.64–6.78)
Q1 (> 0–0. 17)
78
Reference
53
Reference
4
Reference
Q2 (> 0. 17–0. 63)
115
0.89 (0.65–1.22)
89
0.94 (0.65–1.35)
11
1.96 (0.58–6.65)
Q3 (> 0. 63–2.11)
100
0.82 (0.59–1.13)
65
0.78 (0.53–1.15)
15
1.92 (0.59–6.22)
Q4 (> 2.11)
127
0.88 (0.64–1.20)
104
1.04 (0.72–1.51)
8
P-trend3
0.370
0.863
0.89 (0.25–3.21) 0.207
Average lifetime alcohol consumption by types of alcoholic beverage4 Beer (g/d) Nondrinkers Q1 (>0–0. 30)
138
1.33 (0.97–1.82)
93
1.22 (0.84–1.77)
13
1.07 (0.41–2.82)
67
Reference
49
Reference
8
Reference
C 2015 UICC Int. J. Cancer: 137, 1953–1966 (2015) V
Epidemiology
Wine (g/d)
1962
Alcohol consumption and the risk of renal cancers
Table 3. Multivariable-adjusted HR and 95% CIs for renal cancer in relation to baseline and lifetime alcohol consumption in the European Prospective Investigation into Cancer and Nutrition (EPIC) study, 1992–2010. (Continued) Total renal cancer
Renal parenchyma
Renal pelvis
Cases1
HR (95% CI)2
Cases
HR (95% CI)2
Cases
HR (95% CI)2
Q2 (>0. 30 – 1.34)
87
1.03 (0.74–1.43)
68
1.01 (0.69–1.47)
10
0.97 (0.37–2.51)
Q3 (>1.34– 4.83)
109
1.14 (0.81–1.59)
79
1.09 (0.74–1.61)
10
0.57 (0.20–1.57)
Q4 (>4.83)
194
1.30 (0.92–1.85)
144
1.26 (0.84–1.90)
15
0.60 (0.21–1.72)
Alcohol consumption
3
P-trend
0.964
0.798
0.194
Wine (g/d) Nondrinkers
70
1.21 (0.89–1.66)
46
1.07 (0.73–1.56)
7
1.70 (0.57–5.02)
Q1 (>0–1.10)
121
Reference
89
Reference
8
Reference
Q2 (>1.10–3.47)
138
1.04 (0.81–1.33)
103
1.01 (0.76–1.35)
14
1.50 (0.62–3.61)
Q3 (>3.47–8.70)
123
0.98 (0.75–1.27)
84
0.90 (0.66–1.23)
15
1.41 (0.58–3.45)
Q4 (>8.70)
143
0.91 (0.69–1.20)
111
0.91 (0.66–1.26)
12
P-trend3
0.132
0.325
0.97 (0.36–2.61) 0.540
Liquor and spirits (g/d) Nondrinkers
143
1.10 (0.81–1.48)
99
Q1 (>0–0.14)
85
Reference
57
Q2 (>0.14–1.02)
122
1.11 (0.83–1.49)
89
Q3 (>1.02–3.28)
113
0.87 (0.65–1.17)
Q4 (>3.28)
132
0.86 (0.64–1.17)
3
P-trend
0.085
1.14 (0.8–1.64)
13
0.99 (0.39–2.51)
Reference
11
Reference
1.11 (0.78–1.58)
8
1.06 (0.41–2.70)
83
0.90 (0.63–1.29)
14
1.11 (0.49–2.53)
105
0.97 (0.68–1.40)
10
0.75 (0.29–1.92)
0.311
0.707
1
Epidemiology
Number of cases indicates the number of cases with data available for the complete set of variables used in multivariable model; the numbers for all renal cancer subsites include 161 unclear or inconsistent subsite cases and 5 sarcoma cases for which separate subsite analysis was not performed. 2 Multivariate model with age at recruitment (continuous) as the time scale stratified by EPIC study center and adjusted by sex (Male, Female), BMI (categories: 12 – 24
31
0.80 (0.53–1.20)
51
0.82 (0.53–1.28)
42
0.53 (0.32–0.86)
23
0.90 (0.59–1.37)
41
0.59 (0.43–0.82)
69
0.64 (0.39–1.04)
20
0.73 (0.54–0.99)
96
>24 – 60
HR (95% CI) for categories of baseline alcohol consumption (g/d)
8
0.94 (0.55–1.60)
22
1.07 (0.56–2.03)
13
0.81 (0.35–1.92)
6
1.12 (0.60–2.06)
14
0.81 (0.51–1.29)
25
2.19 (0.94–5.08)
6
0.83 (0.55–1.26)
35
>60
0.340
0.029
0.020
0.161
0.002
0.003
0.057
P-trend1
0.066
0.838
0.162
0.377
P-interaction2
Table 4. Multivariable-adjusted HR and 95% CIs for renal cancer by predefined categories of baseline alcohol consumption, according to sex, history of hypertension, smoking status, diabetes status and BMI in the European Prospective Investigation into Cancer and Nutrition (EPIC) study, 1992–2010
Wozniak et al.
1963
Multivariate model
28
1.25 (0.75–2.10)
Cases (n)4
Multivariate model
$30
31
0.93 (0.61–1.43)
Cases (n)4
1.63 (0.98–2.73)
Reference
41
Reference
84
Reference
0.79 (0.48–1.31)
25
0.58 (0.40–0.83)
45
1.13 (0.75–1.70)
>6–12 (men) >3–12 (women)
0.82 (0.48–1.39)
22
0.65 (0.45–0.93)
50
1.13 (0.74–1.73)
>12 – 24
0.78 (0.46–1.31)
26
0.65 (0.46–0.93)
59
0.76 (0.47–1.22)
>24 – 60
0.45 (0.18–1.09)
6
1.16 (0.73–1.84)
27
0.90 (0.41–1.96)
>60
0.023
0.184
0.042
P-trend1
P-interaction2
3
2
Tests for trend were performed by ordinal coding of the variable under consideration. The significance of interactions was assessed using likelihood ratio tests based on the models with and without the interaction terms. Multivariate model with age at recruitment (continuous) as the time scale stratified by EPIC study center and adjusted by BMI (categories:
Alcohol consumption and the risk of renal cancers in the European prospective investigation into cancer and nutrition (EPIC) Magdalena B. Wozniak1, Paul Brennan1, Darren R. Brenner1,2, Kim Overvad3, Anja Olsen4, Anne Tjønneland4, €hn7, Marie-Christine Boutron-Ruault5,6, Franc¸oise Clavel-Chapelon5,6, Guy Fagherazzi5,6, Verena Katzke7, Tilman Ku 8 8 8 9,10 9,10,11 Heiner Boeing , Manuela M. Bergmann , Annika Steffen , Androniki Naska , Antonia Trichopoulou , Dimitrios Trichopoulos10,11,12†, Calogero Saieva13, Sara Grioni14, Salvatore Panico15, Rosario Tumino16, Paolo Vineis17,18, H. B(as) Bueno-de-Mesquita19,20,21,22, Petra H. Peeters23,24, Anette Hjarta˚ker25, Elisabete Weiderpass26,27,28,29, n Alonso de la Torre35, Larraitz Arriola30, Esther Molina-Montes31,32, Eric J. Duell33, Carmen Santiuste34, Ramo 36,37 38,39 1,39 €rje Ljungberg39, Nick Wareham40, Aurelio Barricarte Gurrea , Tanja Stocks , Mattias Johansson , Bo 41 42 17 17 Kay-Tee Khaw , Ruth C. Travis , Amanda J. Cross , Neil Murphy , Elio Riboli17 and Ghislaine Scelo1 1
Genetic Epidemiology Group, International Agency for Research on Cancer (IARC), Lyon, France Department of Population Health Research, Cancer Control Alberta, Alberta Health Services, Calgary, AB, Canada 3 Department of Public Health, Section for Epidemiology, Aarhus University, Aarhus, Denmark 4 Department of Diet, Genes and Environment, Danish Cancer Society Research Center, Copenhagen, Denmark 5 Centre for Research in Epidemiology and Population Health (CESP), INSERM, Villejuif, France 6 Institut Gustave-Roussy (IGR), Universite Paris Sud, INSERM, Villejuif, France 7 Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany 8 €cke, Nuthetal, Germany Department of Epidemiology, German Institute of Human Nutrition (DIfE) Potsdam-Rehbru 9 Department of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School, Athens, Greece 10 Hellenic Health Foundation, Athens, Greece 11 Bureau of Epidemiologic Research, Academy of Athens, Greece 12 Department of Epidemiology, Harvard School of Public Health, Boston, MA 13 Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute (ISPO), Florence, Italy 14 Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale Dei Tumori, Milan, Italy 15 Department of Clinical and Experimental Medicine, Federico II University, Naples, Italy 16 Cancer Registry and Histopathology Unit, "Civic - M.P. Arezzo" Hospital, ASP Ragusa, Italy 17 Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, United Kingdom 18 HuGeF Foundation, Torino, Italy 19 Department for Determinants of Chronic Diseases (DCD), National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands
Key words: kidney cancer, renal cell carcinoma, risk factors, alcohol consumption, EPIC, cohort study Additional Supporting Information may be found in the online version of this article. † Deceased. This work was supported by the US National Cancer Institute (U01-CA155309). The coordination of EPIC is financially supported by the European Commission (DG-SANCO) and the International Agency for Research on Cancer. The national cohorts are supported by: Danish Cancer Society (Denmark); Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Generale de l’Education Nationale, Institut National de la Sante et de la Recherche Medicale (INSERM) (France); Deutsche Krebshilfe, Deutsches Krebsforschungszentrum, Federal Ministry of Education and Research (Germany); Stavros Niarchos Foundation, Hellenic Health Foundation (Greece); Italian Association for Research on Cancer (AIRC), National Research Council, HuGeF Foundation, Compagnia di San Paolo, Sicily Regional Government, AIRE ONLUS Ragusa, AVIS Ragusa (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 Funds (WCRF), Statistics Netherlands (The Netherlands); European Research Council (ERC-2009-AdG232997), Nordforsk (Nordic Center of Excellence programme on Food, Nutrition and Health), Norwegian Research Council, Norwegian Cancer Society, University of Tromso (Norway); Health Research Funds (FIS), Regional Governments of Andalusia, Asturias, Basque Country, Murcia (No. 6236), and Navarra, Instituto de Salud Carlos III (RETIC RD06/0020) (Spain); Swedish Cancer Society, Swedish Scientific Council, Regional Government of Skåne V€asterbotten (Sweden); Cancer Research UK, Medical Research Council (United Kingdom). DOI: 10.1002/ijc.29559 History: Received 6 Nov 2014; Accepted 16 Mar 2015; Online 9 Apr 2015 Correspondence to: Ghislaine Scelo, Genetic Epidemiology Group (GEP), International Agency for Research on Cancer (WHO-IARC), 150 Cours Albert Thomas, 69372 Lyon Cedex 08, France, Tel.: 1[33(0)472738173], Fax: 1[33(0)472738342], E-mail: [email protected]
C 2015 UICC Int. J. Cancer: 137, 1953–1966 (2015) V
Epidemiology
2
1954
Alcohol consumption and the risk of renal cancers
What’s new? Previous studies have indicated that environmental or lifestyle factors may be involved in the etiology of renal cancer, and that moderate alcohol consumption may reduce the risk of this type of cancer. In this very large European study (nearly 500,000 subjects), the authors found that, indeed, total alcohol consumption was inversely associated with renal cancer overall (for all subsites combined), and also with cancers of the renal parenchyma.
20
Department of Gastroenterology and Hepatology, University Medical Centre, Utrecht, The Netherlands Department of Epidemiology and Biostatistics, the School of Public Health, Imperial College London, United Kingdom 22 Department of Social & Preventive Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia 23 Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center, Utrecht, The Netherlands 24 MRC-PHE, Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, United Kingdom 25 Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway 26 Department of Community Medicine, Faculty of Health Sciences, University of Tromsø, The Arctic University of Norway, Tromsø, Norway 27 Cancer Registry of Norway, Oslo, Norway 28 Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden 29 Department of Genetic Epidemiology, Folkh€alsan Research Center, Helsinki, Finland 30 blica (CIBERESP), San Sebastian, Public Health Division of Gipuzkoa, Instituto BIO-Donostia, Basque Government, CIBER De Epidemiologıa Y Salud Pu Spain 31 n Biosanitaria, Universidad De Granada, Granada, Spain blica, Instituto De Investigacio Escuela Andaluza De Salud Pu 32 blica (CIBERESP), Granada, Spain CIBER De Epidemiologıa Y Salud Pu 33 Unit of Nutrition, Environment and Cancer, Cancer Epidemiology Research Program, Catalan Institute of Oncology (ICO), L’hospitalet De Llobregat, Barcelona, Spain 34 Department of Epidemiology, Murcia Regional Health Council, IMIB-Arrixaca, Murcia, Spain 35 Public Health Directorate, Asturias, Spain 36 Navarre Public Health Institute, Pamplona, Spain 37 blica (CIBERESP), Madrid, Spain CIBER De Epidemiologıa Y Salud Pu 38 €, Sweden Department of Clinical Sciences, Lund University, Malmo 39 Department of Surgical and Perioperative Sciences, Urology and Andrology, Umea˚ University, Umea˚, Sweden 40 MRC Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom 41 School of Clinical Medicine, University of Cambridge, Cambridge, United Kingdom 42 Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom
Epidemiology
21
Epidemiologic studies have reported that moderate alcohol consumption is inversely associated with the risk of renal cancer. However, there is no information available on the associations in renal cancer subsites. From 1992 through to 2010, 477,325 men and women in the European Prospective Investigation into Cancer and Nutrition cohort were followed for incident renal cancers (n 5 931). Baseline and lifetime alcohol consumption was assessed by country-specific, validated dietary questionnaires. Information on past alcohol consumption was collected by lifestyle questionnaires. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated from Cox proportional hazard models. In multivariate analysis, total alcohol consumption at baseline was inversely associated with renal cancer; the HR and 95% CI for the increasing categories of total alcohol consumption at recruitment versus the light drinkers category were 0.78 (0.62–0.99), 0.82 (0.64–1.04), 0.70 (0.55–0.90), 0.91 (0.63–1.30), respectively, (ptrend 5 0.001). A similar relationship was observed for average lifetime alcohol consumption and for all renal cancer subsites combined or for renal parenchyma subsite. The trend was not observed in hypertensive individuals and not significant in smokers. In conclusion, moderate alcohol consumption was associated with a decreased risk of renal cancer.
Renal cancers consist of malignant tumors of renal parenchyma and renal pelvis. Adenocarcinoma of renal parenchyma [referred to as renal cell carcinoma (RCC)] accounts for over 90% of renal cancers while nearly all cancers arising in renal pelvis are of the transitional cell type and comprise 0–6 (men) >0–3 (women)
1.6
18.1
2.5
18.3
25.6
54.1
24.5 (4.1)
65.0 (11.0)
163.0 (6.5)
6.9 (2.6)
50.4 (9.9)
100,238 (29.9)
0.93 (0.06)
100.5 (6.6)
93.9 (10.0)
3.2
22.0
1.6
24.9
35.8
37.8
26.2 (3.6)
80.7 (11.8)
175.4 (7.3)
8.9 (1.7)
52.0 (10.8)
23,939 (16.8)
>6–12 (men) >3–12 (women)
1.5
17.6
2.1
20.5
26.4
51.0
24.2 (3.8)
64.1 (10.3)
162.6 (6.5)
16.7 (3.6)
51.0 (9.6)
44,167 (13.2)
0.94 (0.06)
100.6 (6.6)
94.2 (9.8)
3.0
22.3
1.2
27.9
39.6
31.4
26.4 (3.5)
81.0 (11.6)
175.1 (7.2)
17.3 (3.5)
52.6 (9.7)
29,266 (20.6)
>12–24
1.6
17.6
2.2
28.1
28.4
41.4
24.2 (3.8)
64.4 (10.5)
163.0 (6.3)
34.8 (8.8)
51.7 (8.5)
26,261 (7.8)
0.94 (0.06)
101.0 (6.7)
95.1 (9.7)
3.1
22.9
1.0
34.7
39.5
24.9
26.7 (3.5)
81.3 (11.6)
174.5 (7.3)
37.8 (9.8)
52.4 (8.8)
34,576 (24.3)
>24–60
Baseline alcohol consumption (g/d)
2.5
21.6
3.2
39.9
24.5
32.5
24.6 (4.0)
65.8 (11.4)
163.6 (6.1)
76.2 (17.3)
51.8 (8.1)
2,176 (0.7)
0.96 (0.06)
101.9 (7.4)
97.8 (10.5)
4.1
25.4
0.5
49.2
33.9
16.4
27.4 (3.9)
83.2 (12.7)
174.2 (7.2)
82.3 (25.4)
53.0 (7.6)
9,363 (6.6)
>60
Table 2. Baseline characteristics of study participants by total alcohol consumption at recruitment, the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, 1992– 2010
Epidemiology
1958 Alcohol consumption and the risk of renal cancers
C 2015 UICC Int. J. Cancer: 137, 1953–1966 (2015) V
11,539 (2.4) Continuous variables are presented as means and standard deviations (SD), categorical variables are presented as percentages. Unknown values were excluded from the calculations. Percent of missing data were for hypertension, 13.2%; diabetes, 3.5%; waist circumference, 22.4%; hip circumference, 22.4%; waist-hip ratio, 22.4%. 2
931 All Participants (n, %)
476,394
64,134 (13.4)
143,205 (30.0)
124,177 (26.0)
73,433 (15.4)
60,837 (12.8) 1
0.82 (0.08)
100.3 (8.7) 99.7 (8.1)
0.79 (0.07) 0.79 (0.07)
99.5 (8.1) 100.1 (8.7)
0.78 (0.07) 0.79 (0.07)
101.4 (9.6) 104.1 (10.3)
0.81 (0.07) 0.79 (0.07) Waist-hip-ratio2
101.0 (9.3) 102.8 (9.7)
0.82 (0.08)
Hip circumference2 (cm)
82.0 (11.5)
>60 >24–60
79.2 (10.3) 78.3 (10.1) 78.6 (10.7) 80.1 (11.7)
>12–24 Nondrinkers
84.9 (12.4) 80.1 (11.4)
Noncases Cases
84.0 (12.2) Waist circumference2 (cm)
Baseline alcohol consumption (g/d)
>6–12 (men) >3–12 (women) >0–6 (men) >0–3 (women)
Characteristics1
Table 2. Baseline characteristics of study participants by total alcohol consumption at recruitment, the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, 1992– 2010 (Continued)
C 2015 UICC Int. J. Cancer: 137, 1953–1966 (2015) V
hypertension and diabetes showing 31.2 and 7.2% in men and 25.9 and 4.6% in women, respectively. The nonlinear regression analyses for baseline and lifetime alcohol consumption and renal cancer risk for men and women combined are presented in Figures 1 and 2. These nonparametric regression analyses showed evidence of nonlinearity in the association between alcohol consumption and renal cancer risk in the multivariable model for both baseline (p values 5 0.113) and lifetime alcohol consumption (p-value 5 0.035). For both baseline and lifetime alcohol consumption, a linear inverse association was observed in participants with alcohol consumption lower than 10 g/day, this relationship became flat above 10 g/ day. Overall, total baseline and lifetime alcohol consumption were inversely associated with risk of renal cancer (Table 3). In the multivariate model, decreased risks (ptrend 5 0.001) were observed between baseline alcohol consumption and renal cancers combined, compared with light drinkers. This inverse trend remained significant when estimated for drinkers only (ptrend 5 0.047). Similar HRs were observed when diabetes and physical activity were added as covariates to the multivariable model (data not shown). The inverse association for baseline alcohol consumption was mostly driven by the association in renal parenchyma (ptrend 5 0.026) where lower HRs were observed than in renal pelvis. The competing risk analysis provided very similar HRs (Supporting Information Table S1). In addition, similar trends for inverse association have been found in different geographical regions (Supporting Information Table S2). We further assessed associations for specific alcoholic beverages, alcohol consumption from beer, wine, liquor and spirits for men and women combined (Table 3). Among all cohort participants 18% of men and 46% of women were nonbeer drinkers, 13% of men and 20% of women were non-wine drinkers and 28% of men and 56% of women were not drinking spirits and liquor beverages. On average, men had a higher use of alcohol from each beverage for both consumption at recruitment and lifetime. The median consumption for beverages (in grams of alcohol from beverage per day) at recruitment was: beer 4.8 g/d for men and 0.6 g/d for women, wine 5.1 g/d for men and 3.7 g/d for women, liquor and spirits 1.2 g/d for men and 0.4 g/d for women. One type of alcoholic beverage alone was not associated with the risk of all renal cancer subsites combined, when adjusted for other types of alcoholic beverages. Looking at these associations separately by sex did not show strong associations (Supporting Information Tables S3 and S4). There was however a significant inverse association with lifetime consumption of alcohol from liquor and spirits among men (ptrend 5 0.030). A significant inverse association was observed in wine only drinkers, particularly in women where a HR of 0.51 (95% CI 0.31–0.84) was observed
Epidemiology
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Wozniak et al.
Epidemiology
1960
Alcohol consumption and the risk of renal cancers
Figure 1. HRs (solid line) and 95% CIs (gray shade) for baseline alcohol consumption and renal cancer risk evaluated using restricted cubic spline regression (4 knots) for men and women combined in the EPIC cohort. Participants with extreme alcohol consumption of [mt]60 g/day and nondrinkers were excluded. The model was adjusted for age at recruitment, hypertension, sex, BMI, smoking status, waist-to-hip ratio and stratified by center. European Prospective Investigation into Cancer and Nutrition (EPIC), 1992–2010. [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]
Figure 2. HRs (solid line) and 95% CIs (gray shade) for lifetime alcohol consumption and renal cancer risk evaluated using restricted cubic spline regression (4 knots) for men and women combined in the EPIC cohort. Participants with extreme alcohol consumption of more than 60 g/day and nondrinkers were excluded. The model was adjusted for age at recruitment, hypertension, sex, BMI, smoking status, waist-to-hip ratio and stratified by center. European Prospective Investigation into Cancer and Nutrition (EPIC), 1992–2010. [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]
(Supporting Information Table S5). Beer only drinkers also showed an inverse association with renal cancer risk, although not significantly. Table 4 presents the HRs for renal cancer and alcohol consumption at baseline stratified by sex, history of hypertension, smoking status, diabetes and BMI. We found an inverse association between total alcohol consumption and renal cancer in both sexes with stronger effects in women (men: ptrend 5 0.057; women: ptrend 5 0.003). Interestingly, a lower risk of renal cancer was found for participants who declared no history of hypertension. These results were of similar magnitude for lifetime consumption (Supporting Information Table S6). In addition, the associations between baseline and average lifetime alcohol consumption were not modified by sex, hypertension, smoking status, diabetes and BMI as evaluated by likelihood ratio test based on models with and without interaction term. Nonsignificant interactions were observed for alcohol consumption and all variables (all pinteraction > 0.05).
time. We found that alcohol consumption was inversely associated with the risk of renal cancer in men and women. The study supports previous evidence of an inverse association between alcohol consumption and the risk of renal cancers. In addition, this study evaluated alcohol consumption in different renal cancer subsites including renal parenchyma and renal pelvis showing significant inverse associations of moderate alcohol consumption and cancers of renal parenchyma. Interestingly, our data also revealed that individuals with self-reported hypertension did not present lower risk of renal cancers combined in relation to alcohol consumption. Moderate alcohol consumption was inversely associated with renal cancer in our study and supports previous reports of case–control and prospective studies that have shown an inverse association between alcohol consumption and risk of RCC.15–25,39,40 We did not find any clear dose response relationship for the main analyses. The inverse association was observed for all renal cancer subsites combined and subsite of renal parenchyma. However, other cohort11–14,41 and case-control studies8–10 have reported no association. These dissimilarities could be due to different methodologies used to study alcohol consumption and renal cancer risk, quality of data, sample size and varying categories of alcohol consumption.
Discussion In this large prospective European cohort study, we assessed two measures of alcohol consumption. These included alcohol consumption at recruitment, which evaluates recent consumption only as well as alcohol consumption over life-
C 2015 UICC Int. J. Cancer: 137, 1953–1966 (2015) V
1961
Wozniak et al.
Table 3. Multivariable-adjusted HR and 95% CIs for renal cancer in relation to baseline and lifetime alcohol consumption in the European Prospective Investigation into Cancer and Nutrition (EPIC) study, 1992–2010. Total renal cancer Alcohol consumption
Cases1
Renal parenchyma
HR (95% CI)2
Cases
HR (95% CI)2
Renal pelvis Cases
HR (95% CI)2
Baseline (g/d) Nondrinkers
83
1.21 (0.91–1.59)
56
11
2.67 (1.05–6.83)
>0–6 (M)/> 0–3 (W)
170
Reference
131
Reference
1 (0.72–1.39)
10
Reference
>6 – 12 (M)/> 3 – 12 (W)
120
0.78 (0.62–0.99)
92
0.80 (0.61–1.04)
11
1.00 (0.42–2.37)
> 12 – 24
118
0.82 (0.64–1.04)
80
0.72 (0.54–0.96)
15
1.47 (0.65–3.33)
>24 – 60
116
0.70 (0.55–0.90)
86
0.67 (0.50–0.89)
10
0.88 (0.36–2.19)
>60
41
0.91 (0.63–1.30)
34
0.98 (0.66–1.46)
3
0.92 (0.24–3.53)
P-trend3
0.001
0.026
0.112
Average lifetime (g/d) Nondrinkers
42
1.44 (0.99–2.08)
27
1.19 (0.76–1.86)
5
3.04 (0.88–10.55)
Former
31
1.05 (0.70–1.57)
21
0.90 (0.56–1.46)
4
2.00 (0.56–7.09)
>0 – 6 (M)/> 0 – 3 (W)
136
Reference
102
Reference
8
Reference
>6 – 12 (M)/> 3 – 12 (W)
125
0.73 (0.57–0.93)
85
0.66 (0.49–0.88)
21
1.59 (0.70–3.61)
>12 – 24
125
0.86 (0.66–1.11)
92
0.84 (0.62–1.13)
10
0.84 (0.32–2.19)
>24 – 60
104
0.76 (0.57–1.00)
78
0.73 (0.53–1.02)
7
0.67 (0.23–1.96)
>60
32
0.94 (0.61–1.44)
28
1.04 (0.65–1.67)
1
0.43 (0.05–3.83)
P-trend3
0.007
0.138
0.018
4
Baseline alcohol consumption by types of alcoholic beverage Beer (g/d) Nondrinkers
211
1.23 (0.94–1.60)
156
1.16 (0.86–1.57)
18
1.70 (0.59–4.95)
Q1 (> 0–0.43)
98
Reference
80
Reference
5
Reference
Q2 (> 0.43–1.37)
68
1.12 (0.81–1.54)
55
1.15 (0.80–1.65)
7
1.98 (0.60–6.49)
Q3 (> 1.37–5.27)
90
0.99 (0.73–1.35)
57
0.73 (0.51–1.05)
8
1.86 (0.57–6.02)
Q4 (> 5.27)
181
0.96 (0.72–1.29)
131
0.83 (0.59–1.15)
22
2.19 (0.73–6.59)
P-trend3
0.093
0.012
0.418
Nondrinkers
92
1.13 (0.84–1.52)
64
0.98 (0.69–1.38)
10
1.89 (0.68–5.24)
Q1 (> 0–0. 98)
125
Reference
93
Reference
8
Reference
Q2 (> 0. 98–4.42)
156
1.09 (0.86–1.39)
118
1.08 (0.82–1.42)
15
1.52 (0.64–3.62)
Q3 (> 4.42–9.76)
127
0.96 (0.75–1.24)
88
0.90 (0.67–1.22)
15
1.36 (0.56–3.29)
Q4 (> 9.76)
148
0.89 (0.68-1.16)
116
0.89 (0.66-1.22)
12
1.01 (0.39–2.64)
3
P-trend
0.119
0.416
0.420
Liquor and spirits (g/d) Nondrinkers
228
0.94 (0.70–1.26)
168
0.99 (0.70–1.40)
22
2.08 (0.64–6.78)
Q1 (> 0–0. 17)
78
Reference
53
Reference
4
Reference
Q2 (> 0. 17–0. 63)
115
0.89 (0.65–1.22)
89
0.94 (0.65–1.35)
11
1.96 (0.58–6.65)
Q3 (> 0. 63–2.11)
100
0.82 (0.59–1.13)
65
0.78 (0.53–1.15)
15
1.92 (0.59–6.22)
Q4 (> 2.11)
127
0.88 (0.64–1.20)
104
1.04 (0.72–1.51)
8
P-trend3
0.370
0.863
0.89 (0.25–3.21) 0.207
Average lifetime alcohol consumption by types of alcoholic beverage4 Beer (g/d) Nondrinkers Q1 (>0–0. 30)
138
1.33 (0.97–1.82)
93
1.22 (0.84–1.77)
13
1.07 (0.41–2.82)
67
Reference
49
Reference
8
Reference
C 2015 UICC Int. J. Cancer: 137, 1953–1966 (2015) V
Epidemiology
Wine (g/d)
1962
Alcohol consumption and the risk of renal cancers
Table 3. Multivariable-adjusted HR and 95% CIs for renal cancer in relation to baseline and lifetime alcohol consumption in the European Prospective Investigation into Cancer and Nutrition (EPIC) study, 1992–2010. (Continued) Total renal cancer
Renal parenchyma
Renal pelvis
Cases1
HR (95% CI)2
Cases
HR (95% CI)2
Cases
HR (95% CI)2
Q2 (>0. 30 – 1.34)
87
1.03 (0.74–1.43)
68
1.01 (0.69–1.47)
10
0.97 (0.37–2.51)
Q3 (>1.34– 4.83)
109
1.14 (0.81–1.59)
79
1.09 (0.74–1.61)
10
0.57 (0.20–1.57)
Q4 (>4.83)
194
1.30 (0.92–1.85)
144
1.26 (0.84–1.90)
15
0.60 (0.21–1.72)
Alcohol consumption
3
P-trend
0.964
0.798
0.194
Wine (g/d) Nondrinkers
70
1.21 (0.89–1.66)
46
1.07 (0.73–1.56)
7
1.70 (0.57–5.02)
Q1 (>0–1.10)
121
Reference
89
Reference
8
Reference
Q2 (>1.10–3.47)
138
1.04 (0.81–1.33)
103
1.01 (0.76–1.35)
14
1.50 (0.62–3.61)
Q3 (>3.47–8.70)
123
0.98 (0.75–1.27)
84
0.90 (0.66–1.23)
15
1.41 (0.58–3.45)
Q4 (>8.70)
143
0.91 (0.69–1.20)
111
0.91 (0.66–1.26)
12
P-trend3
0.132
0.325
0.97 (0.36–2.61) 0.540
Liquor and spirits (g/d) Nondrinkers
143
1.10 (0.81–1.48)
99
Q1 (>0–0.14)
85
Reference
57
Q2 (>0.14–1.02)
122
1.11 (0.83–1.49)
89
Q3 (>1.02–3.28)
113
0.87 (0.65–1.17)
Q4 (>3.28)
132
0.86 (0.64–1.17)
3
P-trend
0.085
1.14 (0.8–1.64)
13
0.99 (0.39–2.51)
Reference
11
Reference
1.11 (0.78–1.58)
8
1.06 (0.41–2.70)
83
0.90 (0.63–1.29)
14
1.11 (0.49–2.53)
105
0.97 (0.68–1.40)
10
0.75 (0.29–1.92)
0.311
0.707
1
Epidemiology
Number of cases indicates the number of cases with data available for the complete set of variables used in multivariable model; the numbers for all renal cancer subsites include 161 unclear or inconsistent subsite cases and 5 sarcoma cases for which separate subsite analysis was not performed. 2 Multivariate model with age at recruitment (continuous) as the time scale stratified by EPIC study center and adjusted by sex (Male, Female), BMI (categories: 12 – 24
31
0.80 (0.53–1.20)
51
0.82 (0.53–1.28)
42
0.53 (0.32–0.86)
23
0.90 (0.59–1.37)
41
0.59 (0.43–0.82)
69
0.64 (0.39–1.04)
20
0.73 (0.54–0.99)
96
>24 – 60
HR (95% CI) for categories of baseline alcohol consumption (g/d)
8
0.94 (0.55–1.60)
22
1.07 (0.56–2.03)
13
0.81 (0.35–1.92)
6
1.12 (0.60–2.06)
14
0.81 (0.51–1.29)
25
2.19 (0.94–5.08)
6
0.83 (0.55–1.26)
35
>60
0.340
0.029
0.020
0.161
0.002
0.003
0.057
P-trend1
0.066
0.838
0.162
0.377
P-interaction2
Table 4. Multivariable-adjusted HR and 95% CIs for renal cancer by predefined categories of baseline alcohol consumption, according to sex, history of hypertension, smoking status, diabetes status and BMI in the European Prospective Investigation into Cancer and Nutrition (EPIC) study, 1992–2010
Wozniak et al.
1963
Multivariate model
28
1.25 (0.75–2.10)
Cases (n)4
Multivariate model
$30
31
0.93 (0.61–1.43)
Cases (n)4
1.63 (0.98–2.73)
Reference
41
Reference
84
Reference
0.79 (0.48–1.31)
25
0.58 (0.40–0.83)
45
1.13 (0.75–1.70)
>6–12 (men) >3–12 (women)
0.82 (0.48–1.39)
22
0.65 (0.45–0.93)
50
1.13 (0.74–1.73)
>12 – 24
0.78 (0.46–1.31)
26
0.65 (0.46–0.93)
59
0.76 (0.47–1.22)
>24 – 60
0.45 (0.18–1.09)
6
1.16 (0.73–1.84)
27
0.90 (0.41–1.96)
>60
0.023
0.184
0.042
P-trend1
P-interaction2
3
2
Tests for trend were performed by ordinal coding of the variable under consideration. The significance of interactions was assessed using likelihood ratio tests based on the models with and without the interaction terms. Multivariate model with age at recruitment (continuous) as the time scale stratified by EPIC study center and adjusted by BMI (categories:
