Supplementary Table S1. Cohorts Participating in Analysis of Coffee Variables, Liver Cancer

Supplementary Table S1. Cohorts participating in analysis of coffee variables, Liver Cancer Pooling Project.

Cohort / Location / Recruitment/
Follow-up / Cohort
Characteristics / Non-Cases
Total / HCC
Total / ICC
Total
Men / Women / Men / Women / Men / Women
NIH-AARP Diet and
Health Study / multiple states / 1995/2008 / AARP members / 555,887 / 532 / 145
332,457 / 223,430 / 440 / 92 / 102 / 43
Agricultural Health
Study / North Carolina,
Iowa / 1999/2008 / Farmers and spouses / 33,696 / 10 / 2
18,297 / 15,399 / 5 / 5 / 2 / 0
United States
Radiologic Technologists
Study / multiple states / 1994/2008 / U.S. radiologic technologists / 72,402 / 4 / 1
16,112 / 56,290 / 2 / 2 / 1 / 0
Prostate, Lung,
Colorectal, and
Ovarian Cancer
Screening Trial / multiple states / 1993/2009 / Trial of cancer screening modalities / 149,595 / 148 / 41
73,589 / 76,006 / 126 / 22 / 25 / 16
Women's Health Study / multiple states / 1993-1995/2010 / Trial of low-dose aspirin and vitamin
E for preventing CVD and cancer, 1993-2004, then follow-up as an observational study / 39,840 / 6 / 5
- / 39,840 / - / 6 / - / 5
Cancer Prevention
Study II / U.S., nationwide / 1992/2007 / General population / 113,643 / 58 / 9
50,871 / 62,772 / 45 / 13 / 4 / 5
Iowa Women's
Health Study / Iowa / 1986/2007 / Postmenopausal women, ages
55-69 years / 28,570 / 29 / 10
- / 28,570 / - / 29 / - / 10
Black Women's
Health Study / multiple states / 1995/2009 / General population, self-identified
as black or African American / 57,152 / 6 / 1
- / 57,152 / - / 6 / - / 1
Women's Health
Initiative / multiple states / 1993/variable / Postmenopausal women, ages
50-79 years / 160,988 / 67 / 46
- / 160,988 / - / 67 / - / 46
TOTAL / 1,211,773 / 860 / 260
491,326 / 720,447 / 618 / 242 / 134 / 126

Supplementary Table S2. Assessment of coffee consumption, Liver Cancer Pooling Project.

Cohort / Coffee Assessment
NIH-AARP Diet and Health Study / Over the last 12 months, how many cups of coffee, caffeinated or decaffeinated, did you drink? None, Less than 1 cup per month, 1-3 cups per month, 1-2 cups per week, 3-4 cups per week, 5-6 cups per week, 1 cup per day, 2-3 cups per day, 4-5 cups per day, 6+ cups per day
More than half the time, I drank: caffeine-free, caffeine-containing.
Agricultural Health Study / Over the past 12 months, how many cups of coffee, caffeinated or decaffeinated, did you drink? Never, Less than 1 cup per month, 1-3 cups per month, 1 cup per week, 2-4 cups per week, 5-6 cups per week, 1 cup per day, 2-3 cups per day, 4-5 cups per day, 6 or more cups per day
How often was the coffee you drank decaffeinated? Almost never or never, About 1/4 of the time, About 1/2 of the time, About 3/4 of the time, Almost always or always
United States Radiologic
Technologists Study / During the past year, how often did you drink the following beverages?
Coffee, regular (6 oz.) Never, <1/month, 1/month, 2-3/month, 1/week, 2/week, 3-4/week, 5-6/week, 1/day, 2/day, 3/day, 4/day, 5+/day
Coffee, decaffeinated (6 oz.) Never, <1/month, 1/month, 2-3/month, 1/week, 2/week, 3-4/week, 5-6/week, 1/day, 2/day, 3/day, 4/day, 5+/day
Prostate, Lung, Colorectal, and
Ovarian Cancer Screening Trial / Over the past 12 months, How many cups of coffee, caffeinated or decaffeinated, did you drink? None, Less than 1 cup per month, 1-3 cups per month, 1 cup per week, 2-4 cups per week, 5-6 cups per week, 1 cup per day, 2-3 cups per day, 4-5 cups per day, 6 or more cups per day
How often was the coffee you drank decaffeinated? Almost never or never, About 1/4 of the time, About 1/2 of the time, About 3/4 of the time, Almost always or always
Women's Health Study / Please fill in your AVERAGE use, DURING THE PAST YEAR, of each specified food.
Decaffeinated coffee (1 cup): Never or less than once/month, 1-3 per month, 1 per week, 2-4 per week, 5-6 per week, 1 per day, 2-3 per day, 4-5 per day, 6+ per day
Coffee with caffeine (1 cup): Never or less than once/month, 1-3 per month, 1 per week, 2-4 per week, 5-6 per week, 1 per day, 2-3 per day, 4-5 per day, 6+ per day
Cancer Prevention Study II / Please fill in your average total use, during the past year, of each specified food.
Decaffeinated coffee (1 cup): Never, Less than once per month, 1-3 cups per month, 1 cup per week, 2-4 cups per week, 5-6 cups per week, 1 cup per day, 2-3 cups per day, 4-5 cups per day, 6+ cups per day
Coffee with caffeine (1 cup): Never, Less than once per month, 1-3 cups per month, 1 cup per week, 2-4 cups per week, 5-6 cups per week, 1 cup per day, 2-3 cups per day, 4-5 cups per day, 6+ cups per day
Iowa Women's Health Study / Average use during the past year, Coffee (1 cup) Never or less than one per month, 1-3 per mo, 1 per week, 2-4 per week, 5-6 per week, 1 per day, 2-3 per day, 4-5 per day, 6+ per day
Average use during the past year, Decaffeinated coffee (1 cup) Never or less than one per month, 1-3 per mo, 1 per week, 2-4 per week, 5-6 per week, 1 per day, 2-3 per day, 4-5 per day, 6+ per day
Black Women's Health Study / Usual eating habits over the past year:
Decaffeinated coffee - How often: Never or <1 per month, 1-3 per month, 1 per week, 2-4 per week, 5-6 per week, 1 per day, 2-3 per day, 4-5 per day, 6 or more per day; How much (medium serving=1 medium cup): Small, Medium, Large
Coffee, with caffeine - How often: Never or <1 per month, 1-3 per month, 1 per week, 2-4 per week, 5-6 per week, 1 per day, 2-3 per day, 4-5 per day, 6 or more per day; How much (medium serving=1 medium cup): Small, Medium, Large
Women's Health Initiative / Do you usually drink coffee each day?
If yes, how many cups of regular coffee (not decaf) do you usually drink each day? None, 1, 2, 3, 4, 5, 6 or more

Supplementary Table S3. Characteristics of participants in the Liver Cancer Pooling Project by coffee drinking.

Coffee
Non-Drinkers
(N=186,949) / Coffee Drinkers
(N=986,021)
N / (%) / N / (%)
Outcome
Non-Cases / 186,819 / (99.93) / 985,096 / (99.91)
HCC / 93 / (0.05) / 716 / (0.07)
ICC / 37 / (0.02) / 209 / (0.02)
Age at Entry
<50 / 35,932 / (19.22) / 77,647 / (7.87)
50-59 / 56,012 / (29.96) / 292,063 / (29.62)
60-69 / 72,610 / (38.84) / 498,182 / (50.52)
≥70 / 22,395 / (11.98) / 118,129 / (11.98)
Sex
Male / 50,966 / (27.26) / 425,629 / (43.17)
Female / 135,983 / (72.74) / 560,392 / (56.83)
Race
White / 145,683 / (78.66) / 878,132 / (89.76)
Black / 32,501 / (17.55) / 64,094 / (6.55)
Other / 7,016 / (3.79) / 36,033 / (3.68)
Missing / 1,749 / 7,762
Body Mass Index (kg/m2)
<18.5 / 2,311 / (1.27) / 9,063 / (0.94)
18.5-24.9 / 69,112 / (37.89) / 356,389 / (36.94)
25-29.9 / 64,351 / (35.28) / 389,922 / (40.42)
≥30 / 46,631 / (25.56) / 209,380 / (21.70)
Missing / 4,544 / 21,267
Diabetes
No / 173,736 / (93.26) / 912,488 / (92.83)
Yes / 12,561 / (6.74) / 70,514 / (7.17)
Missing / 652 / 3,019
Alcohol (drinks/day)
Non-Drinker / 78,290 / (42.60) / 224,573 / (23.21)
>0-<1 drink / 90,542 / (49.27) / 545,149 / (56.34)
1-3 drinks / 11,021 / (6.00) / 140,550 / (14.53)
>3 drinks / 3,921 / (2.13) / 57,272 / (5.92)
Missing / 3,175 / 18,477
Cigarette Smoking Status
Never Smoker / 120,298 / (65.55) / 391,991 / (40.70)
Former Smoker / 48,274 / (26.30) / 410,495 / (42.62)
Current Smoker / 14,959 / (8.15) / 160,681 / (16.68)
Missing / 3,418 / 22,854
Physical Activity
Low / 70,035 / (41.20) / 421,004 / (46.06)
Medium / 48,578 / (28.57) / 264,639 / (28.95)
High / 51,391 / (30.23) / 228,478 / (24.99)
Missing / 16,945 / 71,900

Supplementary Table S4. Adjusted* Hazard Ratios (HR) and 95% Confidence Intervals (CI) for Associations Between Coffee Consumption and Intrahepatic Cholangiocarcinoma Incidence by Sex, Smoking Status, Body Mass Index, and Diabetes, Liver Cancer Pooling Project.

Men / Women
Coffee Consumption / Non-case N / Case N / HR / 95% CI / Non-case N / Case N / HR / 95% CI
Non-Drinker / 46,615 / 10 / 1.00 / 126,250 / 23 / 1.00
Ever / 393,030 / 105 / 0.99 / ( / 0.51 / - / 1.91 / ) / 508,592 / 94 / 0.90 / ( / 0.56 / - / 1.44 / )
Cups/day
>0-<1 / 73,955 / 21 / 1.16 / ( / 0.54 / - / 2.48 / ) / 90,884 / 15 / 1.16 / ( / 0.58 / - / 2.32 / )
1-<2 / 71,352 / 16 / 0.83 / ( / 0.37 / - / 1.84 / ) / 108,280 / 17 / 0.77 / ( / 0.41 / - / 1.46 / )
2-3 / 170,339 / 44 / 0.92 / ( / 0.46 / - / 1.86 / ) / 200,192 / 41 / 0.95 / ( / 0.56 / - / 1.61 / )
>3 / 76,461 / 24 / 1.11 / ( / 0.52 / - / 2.35 / ) / 84,558 / 16 / 0.89 / ( / 0.46 / - / 1.72 / )
Continuous, cups/day / 1.02 / ( / 0.92 / - / 1.13 / ) / 0.97 / ( / 0.86 / - / 1.09 / )
p for trend† / 0.7 / 0.5
Non-Smokers / Smokers
Coffee Consumption / Non-case N / Case N / HR / 95% CI / Non-case N / Case N / HR / 95% CI
Non-Drinker / 115,235 / 21 / 1.00 / 57,789 / 12 / 1.00
Ever / 374,559 / 65 / 0.82 / ( / 0.49 / - / 1.35 / ) / 527,629 / 134 / 1.11 / ( / 0.61 / - / 2.02 / )
Cups/day
>0-<1 / 87,498 / 17 / 1.13 / ( / 0.58 / - / 2.18 / ) / 77,356 / 19 / 1.25 / ( / 0.60 / - / 2.60 / )
1-<2 / 86,431 / 12 / 0.63 / ( / 0.31 / - / 1.29 / ) / 93,328 / 21 / 0.99 / ( / 0.49 / - / 2.04 / )
2-3 / 140,728 / 26 / 0.82 / ( / 0.46 / - / 1.48 / ) / 230,037 / 59 / 1.09 / ( / 0.58 / - / 2.05 / )
>3 / 47,124 / 9 / 0.89 / ( / 0.40 / - / 1.96 / ) / 113,988 / 31 / 1.19 / ( / 0.60 / - / 2.34 / )
Continuous, cups/day / 0.96 / ( / 0.83 / - / 1.11 / ) / 1.02 / ( / 0.93 / - / 1.12 / )
p for trend† / 0.6 / 0.1
BMI <25 kg/m2 / BMI ≥25 kg/m2
Coffee Consumption / Non-case N / Case N / HR / 95% CI / Non-case N / Case N / HR / 95% CI
Non-Drinker / 67,651 / 10 / 1.00 / 105,214 / 23 / 1.00
Ever / 339,706 / 56 / 0.91 / ( / 0.46 / - / 1.79 / ) / 561,916 / 143 / 0.94 / ( / 0.59 / - / 1.48 / )
Cups/day
>0-<1 / 63,633 / 12 / 1.29 / ( / 0.55 / - / 3.02 / ) / 101,206 / 24 / 1.09 / ( / 0.60 / - / 1.97 / )
1-<2 / 69,237 / 12 / 0.97 / ( / 0.41 / - / 2.25 / ) / 110,395 / 21 / 0.72 / ( / 0.39 / - / 1.31 / )
2-3 / 136,149 / 20 / 0.78 / ( / 0.36 / - / 1.69 / ) / 234,382 / 65 / 0.98 / ( / 0.60 / - / 1.61 / )
>3 / 60,960 / 11 / 0.96 / ( / 0.40 / - / 2.29 / ) / 100,059 / 29 / 1.01 / ( / 0.57 / - / 1.79 / )
Continuous, cups/day / 0.95 / ( / 0.82 / - / 1.11 / ) / 1.01 / ( / 0.92 / - / 1.11 / )
p for trend† / 0.5 / 0.07
No Diabetes / Diabetes
Coffee Consumption / Non-case N / Case N / HR / 95% CI / Non-case N / Case N / HR / 95% CI
Non-Drinker / 161,059 / 29 / 1.00 / 11,391 / 4 / 1.00
Ever / 835,624 / 172 / 0.92 / ( / 0.61 / - / 1.38 / ) / 63,979 / 27 / 1.01 / ( / 0.35 / - / 2.90 / )
Cups/day
>0-<1 / 151,345 / 30 / 1.12 / ( / 0.66 / - / 1.91 / ) / 13,102 / 6 / 1.29 / ( / 0.36 / - / 4.61 / )
1-<2 / 165,484 / 28 / 0.77 / ( / 0.45 / - / 1.31 / ) / 13,769 / 5 / 0.90 / ( / 0.24 / - / 3.36 / )
2-3 / 344,302 / 71 / 0.88 / ( / 0.56 / - / 1.39 / ) / 25,558 / 14 / 1.25 / ( / 0.41 / - / 3.83 / )
>3 / 150,340 / 38 / 1.07 / ( / 0.64 / - / 1.79 / ) / 10,231 / 2 / 0.44 / ( / 0.08 / - / 2.44 / )
Continuous, cups/day / 1.01 / ( / 0.93 / - / 1.10 / ) / 0.90 / ( / 0.72 / - / 1.14 / )
p for trend† / 0.8 / 0.8

*Adjusted for: sex, age (continuous), race (white, black, other), cohort (AARP, AHS, USRT, PLCO, WHS, CPSII, IWHS, BWHS, WHI), BMI (continuous), cigarette smoking intensity (0, ≤10, >10-≤15, >15-≤25, >25 cigarettes/day), alcohol (non-drinker, and >0-<1, 1-3, >3 drinks/day).

†P-value for trend of continuous variable.

Supplementary Table S5. Adjusted* Hazard Ratios (HR) and 95% Confidence Intervals (CI) for Associations Between Coffee Consumption and Hepatocellular Carcinoma and Intrahepatic Cholangiocarcinoma Incidence by Caffeine Content; Sensitivity Analysis Excluding WHI and Jointly Modeling Caffeine Content and Drinking Intensity, Liver Cancer Pooling Project.

Hepatocellular Carcinoma / Intrahepatic Cholangiocarcinoma
Caffeinated Coffee Consumption / HR / 95% CI / HR / 95% CI
Non-Drinker / 130,187 / 63 / 1.00 / 18 / 1.00
Ever / 432,411 / 347 / 1.03 / ( / 0.78 / - / 1.36 / ) / 94 / 1.01 / ( / 0.60 / - / 1.71 / )
Cups/day
>0-<1 / 66,120 / 58 / 1.25 / ( / 0.91 / - / 1.72 / ) / 17 / 1.21 / ( / 0.66 / - / 2.21 / )
1-<2 / 78,850 / 70 / 1.21 / ( / 0.88 / - / 1.67 / ) / 11 / 0.85 / ( / 0.46 / - / 1.59 / )
2-3 / 198,354 / 160 / 0.95 / ( / 0.71 / - / 1.28 / ) / 41 / 0.97 / ( / 0.56 / - / 1.69 / )
>3 / 89,087 / 59 / 0.81 / ( / 0.58 / - / 1.14 / ) / 25 / 1.11 / ( / 0.60 / - / 2.03 / )
p for trend† / 0.2 / 1.0
Decaffeinated Coffee Consumption
Non-Drinker / 130,187 / 63 / 1.00 / 18 / 1.00
Ever / 212,826 / 194 / 1.20 / ( / 0.90 / - / 1.61 / ) / 51 / 1.11 / ( / 0.64 / - / 1.92 / )
Cups/day
>0-<1 / 66,450 / 58 / 1.38 / ( / 1.00 / - / 1.90 / ) / 15 / 1.30 / ( / 0.71 / - / 2.37 / )
1-<2 / 47,791 / 51 / 1.34 / ( / 0.97 / 1.86 / ) / 10 / 0.92 / ( / 0.48 / - / 1.75 / )
2-3 / 75,840 / 64 / 1.05 / ( / 0.77 / - / 1.44 / ) / 20 / 1.04 / ( / 0.58 / - / 1.88 / )
>3 / 22,745 / 21 / 0.90 / ( / 0.63 / - / 1.29 / ) / 6 / 1.19 / ( / 0.62 / - / 2.28 / )
p for trend† / 0.08 / 0.7
Combination Coffee Consumption
Non-Drinker / 130,187 / 63 / 1.00 / 18 / 1.00
Ever / 130,379 / 44 / 0.72 / ( / 0.48 / - / 1.09 / ) / 20 / 1.56 / ( / 0.77 / - / 3.15 / )
Cups/day
>0-<1 / 27,696 / 10 / 0.87 / ( / 0.56 / - / 1.35 / ) / 3 / 1.84 / ( / 0.85 / - / 3.95 / )
1-<2 / 27,098 / 10 / 0.85 / ( / 0.54 / - / 1.31 / ) / 6 / 1.30 / ( / 0.59 / - / 2.85 / )
2-3 / 45,466 / 11 / 0.66 / ( / 0.43 / - / 1.02 / ) / 7 / 1.48 / ( / 0.71 / - / 3.07 / )
>3 / 30,119 / 13 / 0.57 / ( / 0.36 / - / 0.89 / ) / 4 / 1.68 / ( / 0.79 / - / 3.62 / )
p for trend† / 0.4 / 0.2

*Adjusted for: sex, age (continuous), race (white, black, other), cohort (AARP, AHS, USRT, PLCO, WHS, CPSII, IWHS, BWHS, WHI), BMI (continuous), cigarette smoking intensity (cigarettes/day), smoking status (non-smoker, former smoker, current smoker), cigarette smoking intensity (0, ≤10, >10-≤15, >15-≤25, >25 cigarettes/day), alcohol (non-drinker, and >0-<1, 1-3, >3 drinks/day).

†P-value for trend of continuous variable.

Supplementary Table S6. Adjusted* Hazard Ratios (HR) and 95% Confidence Intervals (CI) for Associations Between Coffee Consumption and Suspected Hepatocellular Carcinoma Incidence by Caffeine Content, Liver Cancer Pooling Project.

Total Coffee / Non-case N / Case N / HR / 95% CI
Non-Drinker / 172,865 / 150 / 1.00
Ever / 901,624 / 1,390 / 1.02 / ( / 0.86 / - / 1.22 / )
Cups/day
0 / 172,865 / 150 / 1.00
>0-<1 / 164,840 / 271 / 1.16 / ( / 0.95 / - / 1.42 / )
1-<2 / 179,632 / 289 / 1.11 / ( / 0.91 / - / 1.36 / )
2-3 / 370,532 / 593 / 1.01 / ( / 0.84 / - / 1.21 / )
>3 / 161,019 / 220 / 0.75 / ( / 0.61 / - / 0.94 / )
Continuous, cups/day / 0.92 / ( / 0.89 / - / 0.95 / )
p for trend† / <0.0001
Caffeinated Coffee
Non-Drinker / 172,865 / 150 / 1.00
Ever / 521,438 / 878 / 1.05 / ( / 0.87 / - / 1.26 / )
Cups/day
0 / 172,865 / 150 / 1.00
>0-<1 / 66,120 / 128 / 1.22 / ( / 0.96 / - / 1.56 / )
1-<2 / 102,435 / 177 / 1.19 / ( / 0.95 / - / 1.49 / )
2-3 / 246,378 / 420 / 1.05 / ( / 0.86 / - / 1.28 / )
>3 / 106,505 / 153 / 0.74 / ( / 0.58 / - / 0.95 / )
p for trend† / <0.0001
Decaffeinated Coffee
Non-Drinker / 172,865 / 150 / 1.00
Ever / 232,726 / 408 / 1.06 / ( / 0.87 / - / 1.30 / )
Cups/day‡
0 / 130,187 / 126 / 1.00
>0-<1 / 66,450 / 111 / 1.11 / ( / 0.85 / - / 1.44 / )
1-<2 / 47,791 / 97 / 1.12 / ( / 0.85 / - / 1.47 / )
2-3 / 75,841 / 145 / 1.04 / ( / 0.81 / - / 1.34 / )
>3 / 22,745 / 45 / 0.90 / ( / 0.63 / - / 1.28 / )
p for trend† / 0.3
Combination Coffee
Non-Drinker‡ / 130,187 / 126 / 1.00
Ever / 130,380 / 73 / 0.71 / ( / 0.48 / - / 1.05 / )
Cups/day‡
0 / 130,187 / 126 / 1.00
>0-<1 / 27,697 / 20 / 1.07 / ( / 0.62 / - / 1.84 / )
1-<2 / 27,098 / 12 / 0.56 / ( / 0.29 / - / 1.08 / )
2-3 / 45,466 / 21 / 0.61 / ( / 0.36 / - / 1.05 / )
>3 / 30,119 / 20 / 0.68 / ( / 0.39 / - / 1.18 / )
p for trend† / 0.1

*Adjusted for: sex, age (continuous), race (white, black, other), cohort (AARP, AHS, USRT, PLCO, WHS, CPSII, IWHS, BWHS, WHI), BMI (continuous), cigarette smoking intensity (cigarettes/day), smoking status (non-smoker, former smoker, current smoker), cigarette smoking intensity (0, ≤10, >10-≤15, >15-≤25, >25 cigarettes/day), alcohol (non-drinker, and >0-<1, 1-3, >3 drinks/day).

†P-value for trend of continuous variable.

‡WHI excluded from analysis, due to lack of information about decaffeinated coffee consumption.

Supplementary Table S7. Adjusted* Hazard Ratios (HR) and 95% Confidence Intervals (CI) for Associations Between Coffee Consumption and Hepatocellular Carcinoma and Intrahepatic Cholangiocarcinoma Incidence by Caffeine Content in the AARP Study, Liver Cancer Pooling Project.

Hepatocellular Carcinoma / Intrahepatic Cholangiocarcinoma
Total Coffee / Non-case N / Case N / HR / 95% CI / Case N / HR / 95% CI
Non-Drinker / 54,090 / 33 / 1.00 / 12 / 1.00
Ever / 457,507 / 446 / 1.40 / ( / 0.97 / - / 2.00 / ) / 124 / 1.08 / ( / 0.59 / - / 1.98 / )
Cups/day
0 / 54,090 / 33 / 1.00 / 12 / 1.00
>0-<1 / 83,437 / 87 / 1.60 / ( / 1.07 / - / 2.39 / ) / 24 / 1.23 / ( / 0.61 / - / 2.48 / )
1-<2 / 84,175 / 92 / 1.59 / ( / 1.06 / - / 2.38 / ) / 16 / 0.77 / ( / 0.36 / - / 1.63 / )
2-3 / 209,014 / 196 / 1.32 / ( / 0.90 / - / 1.92 / ) / 55 / 1.04 / ( / 0.55 / - / 1.98 / )
>3 / 80,881 / 71 / 1.11 / ( / 0.72 / - / 1.70 / ) / 29 / 1.38 / ( / 0.69 / - / 2.77 / )
Continuous, cups/day / 0.93 / ( / 0.88 / - / 0.99 / ) / 1.05 / ( / 0.95 / - / 1.16 / )
p for trend† / 0.02 / 0.3
Caffeinated Coffee
Non-Drinker / 54,090 / 33 / 1.00 / 12 / 1.00
Ever / 302,795 / 286 / 1.41 / ( / 0.97 / - / 2.04 / ) / 79 / 1.10 / ( / 0.59 / - / 2.08 / )
Cups/day
0 / 54,090 / 33 / 1.00 / 12 / 1.00
>0-<1 / 40,741 / 44 / 1.62 / ( / 1.03 / - / 2.56 / ) / 11 / 1.22 / ( / 0.53 / - / 2.79 / )
1-<2 / 51,174 / 55 / 1.62 / ( / 1.04 / - / 2.51 / ) / 7 / 0.59 / ( / 0.23 / - / 1.51 / )
2-3 / 148,044 / 136 / 1.37 / ( / 0.92 / - / 2.03 / ) / 38 / 1.11 / ( / 0.57 / - / 2.19 / )
>3 / 62,836 / 51 / 1.11 / ( / 0.70 / - / 1.75 / ) / 23 / 1.54 / ( / 0.73 / - / 3.22 / )
p for trend† / 0.1 / 0.2
Decaffeinated Coffee
Non-Drinker / 54,090 / 33 / 1.00 / 12 / 1.00
Ever / 151,333 / 157 / 1.44 / ( / 0.98 / - / 2.13 / ) / 43 / 1.13 / ( / 0.59 / - / 2.19 / )
Cups/day
0 / 54,090 / 33 / 1.00 / 12 / 1.00
>0-<1 / 42,272 / 43 / 1.58 / ( / 1.00 / - / 2.50 / ) / 12 / 1.21 / ( / 0.54 / - / 2.71 / )
1-<2 / 32,522 / 37 / 1.61 / ( / 1.00 / - / 2.60 / ) / 9 / 1.10 / ( / 0.46 / - / 2.64 / )
2-3 / 59,311 / 59 / 1.32 / ( / 0.85 / - / 2.04 / ) / 17 / 1.11 / ( / 0.51 / - / 2.39 / )
>3 / 17,228 / 18 / 1.23 / ( / 0.68 / - / 2.22 / ) / 5 / 1.10 / ( / 0.37 / - / 3.22 / )
p for trend† / 0.7 / 0.7
Combination Coffee
Non-Drinker / 54,090 / 33 / 1.00 / 12 / 1.00
Ever / 3,379 / 3 / 1.25 / ( / 0.38 / - / 4.16 / ) / 2 / 2.63 / ( / 0.56 / - / 12.23 / )
Cups/day
0 / 54,090 / 33 / 1.00 / 12 / 1.00
>0-<1 / 424 / 0 / – / 1 / 9.55 / ( / 1.23 / - / 74.30 / )
1-<2 / 479 / 0 / – / 0 / –
2-3 / 1,659 / 1 / 0.87 / ( / 0.12 / - / 6.44 / ) / 0 / –
>3 / 817 / 2 / 4.02 / ( / 0.93 / - / 17.32 / ) / 1 / 5.22 / ( / 0.64 / - / 42.69 / )
p for trend† / 0.2 / 0.4

*Adjusted for: sex, age (continuous), race (white, black, other), BMI (continuous), cigarette smoking intensity (cigarettes/day), smoking status (non-smoker, former smoker, current smoker), cigarette smoking intensity (0, ≤10, >10-≤15, >15-≤25, >25 cigarettes/day), alcohol (non-drinker, and >0-<1, 1-3, >3 drinks/day).

†P-value for trend of continuous variable.

Supplementary Table S8. Adjusted* Hazard Ratios (HR) and 95% Confidence Intervals (CI) for Associations Between Coffee Consumption and Hepatocellular Carcinoma and Intrahepatic Cholangiocarcinoma Incidence by Sex in the AARP Study, Liver Cancer Pooling Project.

Hepatocellular Carcinoma
Men / Women
Coffee Consumption / Non-case N / Case N / HR / 95% CI / Non-case N / Case N / HR / 95% CI
Non-Drinker / 28,514 / 23 / 1.00 / 25,576 / 10 / 1.00
Ever / 279,531 / 378 / 1.56 / ( / 1.02 / - / 2.40 / ) / 177,976 / 68 / 1.00 / ( / 0.51 / - / 1.95 / )
Cups/day
>0-<1 / 47,911 / 73 / 1.84 / ( / 1.15 / - / 2.95 / ) / 35,526 / 14 / 1.01 / ( / 0.45 / - / 2.28 / )
1-<2 / 47,194 / 77 / 1.84 / ( / 1.15 / - / 2.94 / ) / 36,981 / 15 / 1.01 / ( / 0.45 / - / 2.24 / )
2-3 / 129,720 / 165 / 1.45 / ( / 0.93 / - / 2.26 / ) / 79,294 / 31 / 1.05 / ( / 0.51 / - / 2.16 / )
>3 / 54,706 / 63 / 1.25 / ( / 0.77 / - / 2.03 / ) / 26,175 / 8 / 0.77 / ( / 0.30 / - / 1.97 / )
Continuous, cups/day / 0.93 / ( / 0.88 / - / 0.99 / ) / 0.94 / ( / 0.82 / - / 1.09 / )
p for trend† / 0.03 / 0.4
Intrahepatic Cholangiocarcinoma
Men / Women
Coffee Consumption / Non-case N / Case N / HR / 95% CI / Non-case N / Case N / HR / 95% CI
Non-Drinker / 28,514 / 7 / 1.00 / 25,576 / 5 / 1.00
Ever / 279,531 / 87 / 1.12 / ( / 0.51 / - / 2.45 / ) / 177,976 / 37 / 1.02 / ( / 0.40 / - / 2.61 / )
Cups/day
>0-<1 / 47,911 / 14 / 1.13 / ( / 0.45 / - / 2.82 / ) / 35,526 / 10 / 1.43 / ( / 0.49 / - / 4.18 / )
1-<2 / 47,194 / 13 / 0.99 / ( / 0.39 / - / 2.51 / ) / 36,981 / 3 / 0.39 / ( / 0.09 / - / 1.63 / )
2-3 / 129,720 / 38 / 1.05 / ( / 0.46 / - / 2.38 / ) / 79,294 / 17 / 1.05 / ( / 0.39 / - / 2.89 / )
>3 / 54,706 / 22 / 1.43 / ( / 0.60 / - / 3.41 / ) / 26,175 / 7 / 1.30 / ( / 0.41 / - / 4.18 / )
Continuous, cups/day / 1.06 / ( / 0.94 / - / 1.19 / ) / 1.03 / ( / 0.86 / - / 1.24 / )
p for trend† / 0.4 / 0.8

*Adjusted for: sex, age (continuous), race (white, black, other), cohort (AARP, AHS, USRT, PLCO, WHS, CPSII, IWHS, BWHS, WHI), BMI (continuous), smoking status (non-smoker, former smoker, current smoker), cigarette smoking intensity (0, ≤10, >10-≤15, >15-≤25, >25 cigarettes/day), alcohol (non-drinker, and >0-<1, 1-3, >3 drinks/day).

†P-value for trend of continuous variable.

Supplementary Table S9. Adjusted* Hazard Ratios (HR) and 95% Confidence Intervals (CI) for Associations Between Coffee Consumption and Hepatocellular Carcinoma and Intrahepatic Cholangiocarcinoma Incidence by Caffeine Content excluding the AARP Study, Liver Cancer Pooling Project.

Hepatocellular Carcinoma / Intrahepatic Cholangiocarcinoma
Total Coffee / Non-case N / Case N / HR / 95% CI / Case N / HR / 95% CI
Non-Drinker / 118,775 / 52 / 1.00 / 21 / 1.00
Ever / 444,115 / 204 / 0.69 / ( / 0.50 / - / 0.96 / ) / 75 / 0.84 / ( / 0.50 / - / 1.40 / )
Cups/day
0 / 118,775 / 52 / 1.00 / 21 / 1.00
>0-<1 / 81,402 / 51 / 1.02 / ( / 0.67 / - / 1.55 / ) / 12 / 1.18 / ( / 0.54 / - / 2.56 / )
1-<2 / 95,457 / 57 / 0.84 / ( / 0.56 / - / 1.24 / ) / 17 / 0.87 / ( / 0.45 / - / 1.68 / )
2-3 / 161,517 / 59 / 0.52 / ( / 0.35 / - / 0.78 / ) / 30 / 0.87 / ( / 0.49 / - / 1.55 / )
>3 / 80,138 / 26 / 0.42 / ( / 0.25 / - / 0.68 / ) / 11 / 0.62 / ( / 0.29 / - / 1.34 / )
Continuous, cups/day / 0.81 / ( / 0.74 / - / 0.89 / ) / 0.91 / ( / 0.79 / - / 1.04 / )
p for trend† / <0.0001 / 0.2
Caffeinated Coffee
Non-Drinker / 118,775 / 52 / 1.00 / 21 / 1.00
Ever / 218,643 / 93 / 0.65 / ( / 0.45 / - / 0.93 / ) / 40 / 0.77 / ( / 0.44 / - / 1.34 / )
Cups/day
0 / 118,775 / 52 / 1.00 / 21 / 1.00
>0-<1 / 25,379 / 14 / 0.97 / ( / 0.52 / - / 1.80 / ) / 6 / 2.62 / ( / 0.95 / - / 7.25 / )
1-<2 / 51,261 / 30 / 0.85 / ( / 0.54 / - / 1.36 / ) / 8 / 0.62 / ( / 0.27 / - / 1.41 / )
2-3 / 98,334 / 38 / 0.59 / ( / 0.38 / - / 0.91 / ) / 19 / 0.74 / ( / 0.39 / - / 1.41 / )
>3 / 43,669 / 11 / 0.33 / ( / 0.16 / - / 0.64 / ) / 7 / 0.62 / ( / 0.26 / - / 1.52 / )
p for trend† / 0.0004 / 0.1
Decaffeinated Coffee
Non-Drinker / 118,775 / 52 / 1.00 / 21 / 1.00
Ever / 81,392 / 47 / 0.86 / ( / 0.56 / - / 1.33 / ) / 13 / 0.77 / ( / 0.37 / - / 1.63 / )
Cups/day‡
0 / 76,097 / 30 / 1.00 / 6 / 1.00
>0-<1 / 24,178 / 15 / 1.01 / ( / 0.53 / - / 1.91 / ) / 3 / 1.08 / ( / 0.26 / - / 4.52 / )
1-<2 / 15,269 / 14 / 1.09 / ( / 0.56 / - / 2.10 / ) / 1 / 0.43 / ( / 0.05 / - / 3.70 / )
2-3 / 16,529 / 5 / 0.32 / ( / 0.12 / - / 0.84 / ) / 3 / 1.32 / ( / 0.30 / - / 5.80 / )
>3 / 5,517 / 3 / 0.45 / ( / 0.13 / - / 1.51 / ) / 1 / 0.90 / ( / 0.10 / - / 8.24 / )
p for trend† / 0.01 / 0.6
Combination Coffee
Non-Drinker‡ / 76,097 / 30 / 1.00 / 6 / 1.00
Ever / 127,000 / 41 / 0.40 / ( / 0.24 / - / 0.67 / ) / 18 / 1.48 / ( / 0.54 / - / 4.04 / )
Cups/day‡
0 / 76,097 / 30 / 1.00 / 6 / 1.00
>0-<1 / 27,272 / 10 / 0.54 / ( / 0.26 / - / 1.13 / ) / 2 / 0.93 / ( / 0.18 / - / 4.76 / )
1-<2 / 26,619 / 10 / 0.46 / ( / 0.22 / - / 0.98 / ) / 6 / 2.33 / ( / 0.71 / - / 7.69 / )
2-3 / 43,807 / 10 / 0.26 / ( / 0.12 / - / 0.55 / ) / 7 / 1.64 / ( / 0.51 / - / 5.29 / )
>3 / 29,302 / 11 / 0.43 / ( / 0.20 / - / 0.89 / ) / 3 / 0.91 / ( / 0.21 / - / 4.02 / )
p for trend† / 0.02 / 0.8

†P-value for trend of continuous variable.

‡WHI excluded from analysis, due to lack of information about decaffeinated coffee consumption.

Supplementary Table S10. Adjusted* Hazard Ratios (HR) and 95% Confidence Intervals (CI) for Associations Between Coffee Consumption and Hepatocellular Carcinoma and Intrahepatic Cholangiocarcinoma Incidence by Sex excluding the AARP Study, Liver Cancer Pooling Project.

Hepatocellular Carcinoma
Men / Women
Coffee Consumption / Non-case N / Case N / HR / 95% CI / Non-case N / Case N / HR / 95% CI
Non-Drinker / 18,101 / 17 / 1.00 / 100,674 / 35 / 1.00
Ever / 113,499 / 112 / 0.71 / ( / 0.42 / - / 1.21 / ) / 330,616 / 92 / 0.68 / ( / 0.45 / - / 1.02 / )
Cups/day
>0-<1 / 26,044 / 40 / 1.12 / ( / 0.63 / - / 1.99 / ) / 55,358 / 11 / 0.70 / ( / 0.34 / - / 1.45 / )
1-<2 / 24,158 / 26 / 0.67 / ( / 0.36 / - / 1.25 / ) / 71,299 / 31 / 1.03 / ( / 0.63 / - / 1.69 / )
2-3 / 40,619 / 30 / 0.51 / ( / 0.27 / - / 0.93 / ) / 120,898 / 29 / 0.53 / ( / 0.32 / - / 0.88 / )
>3 / 21,755 / 16 / 0.48 / ( / 0.24 / - / 0.96 / ) / 58,383 / 10 / 0.33 / ( / 0.16 / - / 0.68 / )
Continuous, cups/day / 0.81 / ( / 0.71 / - / 0.92 / ) / 0.81 / ( / 0.71 / - / 0.92 / )
p for trend† / 0.001 / 0.002
Intrahepatic Cholangiocarcinoma
Men / Women
Coffee Consumption / Non-case N / Case N / HR / 95% CI / Non-case N / Case N / HR / 95% CI
Non-Drinker / 18,101 / 3 / 1.00 / 100,674 / 18 / 1.00
Ever / 113,499 / 18 / 0.66 / ( / 0.19 / - / 2.30 / ) / 330,616 / 57 / 0.87 / ( / 0.51 / - / 1.51 / )
Cups/day
>0-<1 / 26,044 / 7 / 1.20 / ( / 0.31 / - / 4.72 / ) / 55,358 / 5 / 0.86 / ( / 0.30 / - / 2.50 / )
1-<2 / 24,158 / 3 / 0.46 / ( / 0.09 / - / 2.34 / ) / 71,299 / 14 / 0.98 / ( / 0.48 / - / 2.00 / )
2-3 / 40,619 / 6 / 0.62 / ( / 0.15 / - / 2.54 / ) / 120,898 / 24 / 0.91 / ( / 0.49 / - / 1.71 / )
>3 / 21,755 / 2 / 0.34 / ( / 0.05 / - / 2.05 / ) / 58,383 / 9 / 0.70 / ( / 0.30 / - / 1.62 / )
Continuous, cups/day / 0.84 / ( / 0.63 / - / 1.13 / ) / 0.93 / ( / 0.80 / - / 1.08 / )
p for trend† / 0.3 / 0.01

†P-value for trend of continuous variable.

Supplementary Figure S1. Meta-influence Graph of the Influence of Individuals Studies for Associations between Coffee Consumption versus No Consumption and Hepatocellular Carcinoma, Liver Cancer Pooling Project.