Abstract
Background
Objective
Design
Participants/setting
Main outcome measure
Statistical analyses performed
Results
Conclusions
Keywords
Materials and Methods
Study Population and Cancer Follow-Up

Exposure Assessment
Mediterranean Diet Adherence
Statistical Analyses
Results
Characteristic | Men | Women | ||
---|---|---|---|---|
Subcohort (n = 2057) | Cancer cases (n = 13,657) | Subcohort (n = 2027) | Cancer cases (n = 8571) | |
←median (IQR)→ | ||||
Age (y) | 61 (7) | 62 (7) | 61 (7) | 61 (7) |
←%→ | ||||
Current cigarette smokers | 35.1 | 40.3 | 21.3 | 23.1 |
Higher vocational education or university | 19.3 | 19.6 | 9.5 | 9.1 |
←mean (SD)→ | ||||
Body mass index | 24.9 (2.6) | 25.0 (2.6) | 25.0 (3.5) | 25.2 (3.6) |
←median (IQR)→ | ||||
Height (cm) | 176 (9) | 176 (9) | 165 (8) | 166 (8) |
Nonoccupational physical activity (min/d) | 62.1 (67.1) | 64.3 (65.7) | 54.3 (52.9) | 51.4 (53.6) |
←%→ | ||||
Family history of cancer | 45.1 | 48.2 | 47.3 | 51.5 |
←median (IQR)→ | ||||
Age at menarche (y) | 13 (3) | 13 (3) | ||
Age at menopause (y) | 50 (6) | 50 (6) | ||
←%→ | ||||
Nulliparous | 18.5 | 19.1 | ||
←% of parous→ | ||||
Age at first birth ≥30 y | 22.5 | 23.3 | ||
←%→ | ||||
Ever use of oral contraceptives | 25.4 | 24.5 | ||
Ever use of hormone replacement therapy | 13.4 | 13.3 | ||
←mean (SD)→ | ||||
aMEDr | 3.9 (1.6) | 3.9 (1.6) | 4.0 (1.6) | 3.9 (1.6) |
aMED | 4.3 (1.7) | 4.3 (1.7) | 4.3 (1.7) | 4.2 (1.7) |
Food intake (g/d) | ←median (IQR)→ | |||
Vegetables | 207.3 (123.9) | 205.3 (116.4) | 219.2 (121.1) | 218.2 (122.1) |
Legumes | 6.5 (15.9) | 6.6 (16.0) | 4.7 (12.2) | 4.7 (11.8) |
Fruits | 157.0 (157.2) | 154.4 (162.2) | 209.4 (176.5) | 210.5 (178.1) |
Nuts | 3.3 (11.0) | 3.2 (10.4) | 1.7 (6.1) | 1.5 (5.7) |
Whole grains | 0.0 (9.7) | 0.0 (9.4) | 0.0 (13.1) | 0.0 (11.8) |
Fish | 11.5 (22.8) | 11.7 (21.7) | 8.7 (21.9) | 8.6 (21.2) |
Red and processed meat | 125.1 (62.8) | 124.7 (65.8) | 106.4 (61.2) | 106.1 (63.0) |
MUFA:SFA ratio | 0.98 (0.24) | 0.98 (0.23) | 0.94 (0.21) | 0.93 (0.22) |
Alcohol | 9.7 (20.9) | 11.4 (22.0) | 1.6 (7.8) | 1.5 (8.6) |
←mean (SD)→ | ||||
Daily energy intake (kcal) | 2162 (501) | 2165 (494) | 1687 (392) | 1682 (386) |
aMED | |||||
---|---|---|---|---|---|
0-3 | 4-5 | 6-8 | Ptrend | Continuous, per 2 points | |
Men | |||||
Excluding alcohol (aMEDr) | |||||
PYsubcohort/cases | 11,189/5068 | 11,773/5243 | 4416/1873 | 27,378/12,184 | |
HR age (95% CI) | 1.00 | 0.99 (0.88-1.12) | 0.92 (0.78-1.07) | .294 | 0.98 (0.92-1.05) |
HR multivariable-adjusted (95% CI) h Adjusted for age at baseline (years), cigarette smoking status (never, former, current), cigarette smoking frequency (cigarettes smoked per day, centered), cigarette smoking duration (years, centered), body mass index (<18.5, ≥18.5 to <25.0, ≥25.0 to <30.0, ≥30.0), height (cm), alcohol consumption (0, >0 to <5, ≥5 to <15, ≥15 to <30, ≥30 g/d), daily energy intake (kcal), highest level of education (primary school or lower vocational, secondary school or medium vocational, higher vocational or university), nonoccupational physical activity (≤30, >30 to ≤60, >60 to ≤90, >90 min/d), and family history of cancer (no, yes). | 1.00 | 1.00 (0.88-1.13) | 0.99 (0.84-1.17) | .948 | 1.02 (0.95-1.10) |
Including alcohol (aMED) | |||||
PYsubcohort/cases | 8690/4014 | 12,191/5292 | 6,497/2,878 | 27,378/12,184 | |
HR multivariable-adjusted (95% CI) h Adjusted for age at baseline (years), cigarette smoking status (never, former, current), cigarette smoking frequency (cigarettes smoked per day, centered), cigarette smoking duration (years, centered), body mass index (<18.5, ≥18.5 to <25.0, ≥25.0 to <30.0, ≥30.0), height (cm), alcohol consumption (0, >0 to <5, ≥5 to <15, ≥15 to <30, ≥30 g/d), daily energy intake (kcal), highest level of education (primary school or lower vocational, secondary school or medium vocational, higher vocational or university), nonoccupational physical activity (≤30, >30 to ≤60, >60 to ≤90, >90 min/d), and family history of cancer (no, yes). | 1.00 | 0.96 (0.85-1.10) | 1.02 (0.88-1.19) | .996 | 1.02 (0.95-1.09) |
Women | |||||
Excluding alcohol (aMEDr) | |||||
PYsubcohort/cases | 10,191/2843 | 12,537/3003 | 5328/1225 | 28,056/7071 | |
HR age (95% CI) | 1.00 | 0.87 (0.77-0.98) | 0.84 (0.72-0.99) | .030 | 0.91 (0.85-0.98) |
HR multivariable-adjusted (95% CI) h Adjusted for age at baseline (years), cigarette smoking status (never, former, current), cigarette smoking frequency (cigarettes smoked per day, centered), cigarette smoking duration (years, centered), body mass index (<18.5, ≥18.5 to <25.0, ≥25.0 to <30.0, ≥30.0), height (cm), alcohol consumption (0, >0 to <5, ≥5 to <15, ≥15 to <30, ≥30 g/d), daily energy intake (kcal), highest level of education (primary school or lower vocational, secondary school or medium vocational, higher vocational or university), nonoccupational physical activity (≤30, >30 to ≤60, >60 to ≤90, >90 min/d), and family history of cancer (no, yes). j Analyses conducted among women were additionally adjusted for age at menarche (≤12, 13-14, 15-16, ≥17 years), parity (nulliparous, 1-2, ≥3 children), age at first birth (<25, ≥25 years), age at menopause (≤44, 45-49, 50-54, ≥55 years), oral contraceptive use (never, ever), and use of postmenopausal hormone replacement therapy (never, ever). | 1.00 | 0.85 (0.75-0.97) | 0.90 (0.76-1.06) | .188 | 0.93 (0.86-1.01) |
Including alcohol (aMED) | |||||
PYsubcohort/cases | 8,939/2461 | 12,149/3024 | 6969/1586 | 28,056/7071 | |
HR multivariable-adjusted (95% CI) h Adjusted for age at baseline (years), cigarette smoking status (never, former, current), cigarette smoking frequency (cigarettes smoked per day, centered), cigarette smoking duration (years, centered), body mass index (<18.5, ≥18.5 to <25.0, ≥25.0 to <30.0, ≥30.0), height (cm), alcohol consumption (0, >0 to <5, ≥5 to <15, ≥15 to <30, ≥30 g/d), daily energy intake (kcal), highest level of education (primary school or lower vocational, secondary school or medium vocational, higher vocational or university), nonoccupational physical activity (≤30, >30 to ≤60, >60 to ≤90, >90 min/d), and family history of cancer (no, yes). j Analyses conducted among women were additionally adjusted for age at menarche (≤12, 13-14, 15-16, ≥17 years), parity (nulliparous, 1-2, ≥3 children), age at first birth (<25, ≥25 years), age at menopause (≤44, 45-49, 50-54, ≥55 years), oral contraceptive use (never, ever), and use of postmenopausal hormone replacement therapy (never, ever). | 1.00 | 0.91 (0.79-1.04) | 0.88 (0.75-1.03) | .139 | 0.94 (0.87-1.01) |
aMEDr in Men b Adjusted for age at baseline (years), cigarette smoking status (never, former, current), cigarette smoking frequency (cigarettes smoked per day, centered), cigarette smoking duration (years, centered), body mass index (<18.5, ≥18.5 to <25.0, ≥25.0 to <30.0, ≥30.0), height (cm), alcohol consumption (0, >0 to <5, ≥5 to <15, ≥15 to <30, ≥30 g/d), daily energy intake (kcal), highest level of education (primary school or lower vocational, secondary school or medium vocational, higher vocational or university), nonoccupational physical activity (≤30, >30 to ≤60, >60 to ≤90, >90 min/d), and family history of cancer (no, yes). | aMEDr in Women b Adjusted for age at baseline (years), cigarette smoking status (never, former, current), cigarette smoking frequency (cigarettes smoked per day, centered), cigarette smoking duration (years, centered), body mass index (<18.5, ≥18.5 to <25.0, ≥25.0 to <30.0, ≥30.0), height (cm), alcohol consumption (0, >0 to <5, ≥5 to <15, ≥15 to <30, ≥30 g/d), daily energy intake (kcal), highest level of education (primary school or lower vocational, secondary school or medium vocational, higher vocational or university), nonoccupational physical activity (≤30, >30 to ≤60, >60 to ≤90, >90 min/d), and family history of cancer (no, yes). c Analyses conducted among women were additionally adjusted for age at menarche (≤12, 13-14, 15-16, ≥17 years), parity (nulliparous, 1-2, ≥3 children), age at first birth (<25, ≥25 years), age at menopause (≤44, 45-49, 50-54, ≥55 years), oral contraceptive use (never, ever), and use of postmenopausal hormone replacement therapy (never, ever). | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
0-3 | 4-5 | 6-8 | Ptrend | Continuous | 0-3 | 4-5 | 6-8 | Ptrend | Continuous | |
All cancers | ||||||||||
PYsubcohort | 11,189 | 11,773 | 4416 | 27,378 | 10,191 | 12,537 | 5328 | 28,056 | ||
Cases | 5068 | 5243 | 1873 | 12,184 | 2843 | 3003 | 1225 | 7071 | ||
HR (95% CI) | 1.00 | 1.00 (0.88-1.13) | 0.99 (0.84-1.17) | .948 | 1.02 (0.95-1.10) | 1.00 | 0.85 (0.75-0.97) | 0.90 (0.76-1.06) | .188 | 0.93 (0.86-1.01) |
Smoking related | ||||||||||
Cases | 2943 | 2835 | 945 | 6723 | 1236 | 1261 | 516 | 3013 | ||
HR (95% CI) | 1.00 | 0.95 (0.83-1.08) | 0.96 (0.80-1.14) | .559 | 0.99 (0.92-1.07) | 1.00 | 0.85 (0.73-0.98) | 0.90 (0.74-1.09) | .245 | 0.92 (0.84-1.01) |
Not smoking related | ||||||||||
Cases | 2125 | 2408 | 928 | 5461 | 1607 | 1742 | 709 | 4058 | ||
HR (95% CI) | 1.00 | 1.08 (0.95-1.23) | 1.05 (0.88-1.25) | .583 | 1.06 (0.98-1.14) | 1.00 | 0.86 (0.75-0.99) | 0.90 (0.75-1.07) | .221 | 0.94 (0.87-1.02) |
Obesity related | ||||||||||
Cases | 1159 | 1292 | 490 | 2941 | 1933 | 2085 | 865 | 4883 | ||
HR (95% CI) | 1.00 | 1.07 (0.93-1.23) | 1.06 (0.88-1.28) | .506 | 1.06 (0.98-1.15) | 1.00 | 0.85 (0.75-0.98) | 0.91 (0.77-1.08) | .277 | 0.94 (0.87-1.02) |
Not obesity related | ||||||||||
Cases | 3909 | 3951 | 1383 | 9243 | 910 | 918 | 360 | 2188 | ||
HR (95% CI) | 1.00 | 0.98 (0.86-1.11) | 0.97 (0.82-1.16) | .740 | 1.01 (0.94-1.08) | 1.00 | 0.85 (0.73-1.00) | 0.87 (0.71-1.07) | .172 | 0.92 (0.84-1.01) |
Alcohol related | ||||||||||
Cases | 954 | 1030 | 401 | 2385 | 1501 | 1580 | 675 | 3756 | ||
HR (95% CI) | 1.00 | 1.03 (0.89-1.20) | 1.08 (0.89-1.32) | .432 | 1.03 (0.95-1.13) | 1.00 | 0.83 (0.72-0.96) | 0.92 (0.77-1.10) | .322 | 0.93 (0.86-1.01) |
Not alcohol related | ||||||||||
Cases | 4114 | 4213 | 1472 | 9799 | 1342 | 1423 | 550 | 3315 | ||
HR (95% CI) | 1.00 | 0.99 (0.87-1.12) | 0.97 (0.82-1.15) | .753 | 1.02 (0.95-1.09) | 1.00 | 0.88 (0.76-1.01) | 0.88 (0.73-1.06) | .152 | 0.93 (0.86-1.01) |
Overall Cancer Risk | ||||
---|---|---|---|---|
Men | Women | |||
Cases | HR (95% CI) e Adjusted for age at baseline (years), cigarette smoking status (never, former, current), cigarette smoking frequency (cigarettes smoked per day, centered), cigarette smoking duration (years, centered), body mass index (<18.5, ≥18.5 to <25.0, ≥25.0 to <30.0, ≥30.0), height (cm), alcohol consumption (0, >0 to <5, ≥5 to <15, ≥15 to <30, ≥30 g/d), daily energy intake (kcal), highest level of education (primary school or lower vocational, secondary school or medium vocational, higher vocational or university), nonoccupational physical activity (≤30, >30 to ≤60, >60 to ≤90, >90 min/d), and family history of cancer (no, yes). | Cases | HR (95% CI) e Adjusted for age at baseline (years), cigarette smoking status (never, former, current), cigarette smoking frequency (cigarettes smoked per day, centered), cigarette smoking duration (years, centered), body mass index (<18.5, ≥18.5 to <25.0, ≥25.0 to <30.0, ≥30.0), height (cm), alcohol consumption (0, >0 to <5, ≥5 to <15, ≥15 to <30, ≥30 g/d), daily energy intake (kcal), highest level of education (primary school or lower vocational, secondary school or medium vocational, higher vocational or university), nonoccupational physical activity (≤30, >30 to ≤60, >60 to ≤90, >90 min/d), and family history of cancer (no, yes). f Analyses conducted among women were additionally adjusted for age at menarche (≤12, 13-14, 15-16, ≥17 years), parity (nulliparous, 1-2, ≥3 children), age at first birth (<25, ≥25 years), age at menopause (≤44, 45-49, 50-54, ≥55 years), oral contraceptive use (never, ever), and use of postmenopausal hormone replacement therapy (never, ever). | |
Overall | 12,184 | 1.02 (0.95-1.10) | 7071 | 0.93 (0.86-1.01) |
Cigarette smoking status | ||||
Never | 1367 | 0.99 (0.82-1.20) | 3970 | 0.93 (0.85-1.03) |
Former | 6084 | 1.05 (0.96-1.15) | 1490 | 0.87 (0.72-1.04) |
Current | 4733 | 0.98 (0.85-1.12) | 1611 | 0.97 (0.81-1.18) |
Pinteraction | .801 | .363 | ||
Alcohol consumption | ||||
0 g/d | 1488 | 1.03 (0.86-1.24) | 2166 | 0.91 (0.78-1.05) |
>0 to <15.0 g/d | 5616 | 1.07 (0.97-1.19) | 3838 | 0.97 (0.88-1.07) |
≥15.0 g/d | 5080 | 0.95 (0.84-1.07) | 1067 | 0.80 (0.63-1.00) |
Pinteraction | .344 | .532 | ||
Body mass index | ||||
≥18.5 to <25.0 | 6310 | 0.99 (0.89-1.09) | 3699 | 0.91 (0.82-1.01) |
≥25.0 | 5826 | 1.07 (0.96-1.19) | 3293 | 0.93 (0.82-1.04) |
Pinteraction | .263 | .740 | ||
Highest level of education | ||||
Primary school or lower vocational | 5430 | 0.96 (0.86-1.08) | 3742 | 0.87 (0.79-0.97) |
Secondary school or medium vocational | 4319 | 1.04 (0.93-1.16) | 2643 | 0.96 (0.84-1.10) |
Higher vocational or university | 2435 | 1.19 (1.01-1.41) | 686 | 1.19 (0.91-1.57) |
Pinteraction | .049 | .408 | ||
Family history of cancer | ||||
No | 6267 | 1.06 (0.96-1.17) | 3375 | 0.94 (0.84-1.04) |
Yes | 5917 | 0.98 (0.89-1.09) | 3696 | 0.94 (0.84-1.04) |
Pinteraction | .261 | .785 |
Discussion
Conclusions
Acknowledgements
Author Contributions
References
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STATEMENT OF POTENTIAL CONFLICT OF INTEREST No potential conflict of interest was reported by the authors.
FUNDING/SUPPORT This study was funded by Wereld Kanker Onderzoek Fonds Nederland (WCRF-NL), as part of the World Cancer Research Fund International grant program (grant number 2015/1390 to P. A. van den Brandt). WCRF-NL had no role in the design, analysis, or writing of this article.
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