Citrus fruit and pancreatic cancer.

Pancreatic cancer risk: Data about the relation with pancreatic cancer risk was provided by 5 cohorts. No (non)significant associations were found in any cohort at any level of consumption.

Pancreatic cancer mortality: Data about the relation with pancreatic cancer mortality was provided by 3 cohorts. A nonsignificant protective effect was found in one cohort with very few cancer cases (1). No other associations were found.

Conclusion: No significant associations were found. No evidence was found for an association between citrus fruit and pancreatic cancer.

**Prospective studies of citrus fruit and pancreatic cancer risk:**
Author	Cohort name	Subjects	Years of follow-up	Cases	End point	Consumption of	Relative Risk (RR)	Adjustments
18) Vrieling A (2009)	The EPIC Study	478,400 subjects from 10 European countries.	8.9 (1991-2000 to 2002-2007)	555	Invasive exocrine pancreatic cancer incidence	Citrus fruit (not defined)	HR = 1.12 (0.86-1.45; P = 0.38) for the highest vs lowest quartile of consumption. Amount specific data (g/day): < 8: HR = 1. 8-29: HR = 1.00 (0.79-1.28). 29-68: HR = 0.92 (0.72-1.19). > 68: HR = 1.12 (0.86-1.45).	Stratified by age at entry, sex and center. Adjusted for energy from fat, energy from non-fat, weight, height, history of diabetes, and smoking status. Waist-to-hip ratio, alcohol, red meat and processed meat intake, and education did not markedly change the risk estimates.
16) Nöthlings U (2007)	The Multiethnic Cohort Study	162,150 subjects (72,966 men and 89,184 women) aged 45-75. (Hawaii-Los Angeles)	8 (1993-96 to 2002)	434	Exocrine pancreatic cancer incidence	Citrus fruit (not defined)	RR = 1.08 (0.82-1.43; P = 0.63) for the highest vs lowest quartile of consumption. Amount specific data (g/1000 kcal./d): < 13.4: RR = 1. 13.4-40.7: RR = 1.03 (0.78-1.35). 40.7-93.9: RR = 1.02 (0.77-1.34). ≥ 93.9: RR = 1.08 (0.82-1.43). There was little evidence of effect modification by smoking status (never, former, or current).	Controlled for sex and time on study. Adjusted for race-ethnicity, age at cohort entry, smoking status, pack-years of smoking, family history of pancreatic cancer, energy intake, intakes of red meat and processed meat, and BMI.
14) Larsson SC (2006)	The Swedish Mammography Cohort & The Cohort of Swedish Men	81,922 subjects (36,616 women and 45,306 men).	6.8 (1998-2004)	135 (61 women and 74 men)	Primary malignant neoplasm of the exocrine pancreas incidence	Citrus fruits (oranges, grapefruits, orange/grapefruit juice, and other citrus fruits)	HR = 1.12 (0.68-1.83; P = 0.53) for the highest vs lowest quartile of consumption. Amount specific data (servings/wk): < 1.0: HR = 1. 1.0-2.9: HR = 0.88 (0.52-1.50). 3.0-6.9: HR = 1.26 (0.81-2.00). ≥ 7.0: HR = 1.12 (0.68-1.83).	Age, sex, education, BMI, physical activity, cigarette smoking status and pack-years of smoking, multivitamin supplement use, and intakes of total energy, alcohol, green leafy vegetables and cruciferous vegetables.
6) Bobe G (2008)	The Alpha-Tocopherol, beta-Carotene Cancer Prevention Study (ATBC)	27,111 healthy male smokers of ≥ 5 cigarettes/day aged 50-69. (Finland)	16.1 (1985-2004)	306	Primary exocrine adenocarcinoma of the pancreas incidence	Citrus fruits (not defined)	HR = 1.05 (0.74-1.49; P = 0.84) for the highest vs lowest quintile of consumption. Amount specific data (g/day): ≤ 4.43: HR = 1. > 4.43-13.99: HR = 1.05 (0.75-1.48). 14.00-27.72: HR = 0.85 (0.59-1.22). > 27.72-58.79: HR = 0.84 (0.58-1.20). > 58.80: HR = 1.05 (0.74-1.49). Effect modification: No significant interaction was found by intervention (any supplement [alpha-tocopherol, beta-carotene, or both] vs placebo).	Age at randomization, years of smoking, total number of cigarettes per day, self-reported history of diabetes mellitus, and energy-adjusted saturated fat intake.
6) Stolzenberg-Solomon RZ (2002)	The Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study (ATBC).	27,111 male smokers of ≥ 5 cigarettes/day aged 50-69. (Finland)	13 (1985-88 to 1997)	163?	Primary malignant neoplasm of the exocrine pancreas incidence	Citrus fruits (not defined)	HR = 0.79 (0.47-1.31; P = 0.53) for the highest vs lowest quintile of consumption. Amount specific data (g/day): ≤ 5.3: HR = 1. > 5.3 and ≤ 22.6: HR = 1.15 (0.73-1.82). > 22.6 and ≤ 46.2: HR = 0.74 (0.44-1.23). > 46.2 and ≤ 90.9: HR = 1.14 (0.72-1.81). > 90.9: HR = 0.79 (0.47-1.31).	Energy intake, age and years of smoking. Additional variables examined in the analyses included ATBC trial interventions; dietary folate, saturated fat, and carbohydrate intakes; history of diabetes mellitus; occupational physical activity; and education.

Prospective studies of citrus fruit and pancreatic cancer risk:

Author

Cohort name

Subjects

Years of follow-up

Cases

End point

Consumption of

Relative Risk (RR)

Adjustments

18) Vrieling A (2009)

The EPIC Study

478,400 subjects from 10 European countries.

8.9
(1991-2000 to 2002-2007)

555

Invasive exocrine pancreatic cancer incidence

Citrus fruit (not defined)

HR = 1.12 (0.86-1.45; P = 0.38) for the highest vs lowest quartile of consumption.

Amount specific data (g/day):
< 8: HR = 1.
8-29: HR = 1.00 (0.79-1.28).
29-68: HR = 0.92 (0.72-1.19).
> 68: HR = 1.12 (0.86-1.45).

Stratified by age at entry, sex and center. Adjusted for energy from fat, energy from non-fat, weight, height, history of diabetes, and smoking status.

Waist-to-hip ratio, alcohol, red meat and processed meat intake, and education did not markedly change the risk estimates.

16) Nöthlings U (2007)

The Multiethnic Cohort Study

162,150 subjects (72,966 men and 89,184 women) aged 45-75.
(Hawaii-Los Angeles)

8
(1993-96 to 2002)

434

Exocrine pancreatic cancer incidence

Citrus fruit (not defined)

RR = 1.08 (0.82-1.43; P = 0.63) for the highest vs lowest quartile of consumption.

Amount specific data (g/1000 kcal./d):
< 13.4: RR = 1.
13.4-40.7: RR = 1.03 (0.78-1.35).
40.7-93.9: RR = 1.02 (0.77-1.34).
≥ 93.9: RR = 1.08 (0.82-1.43).

There was little evidence of effect modification by smoking status (never, former, or current).

Controlled for sex and time on study. Adjusted for race-ethnicity, age at cohort entry, smoking status, pack-years of smoking, family history of pancreatic cancer, energy intake, intakes of red meat and processed meat, and BMI.

14) Larsson SC (2006)

The Swedish Mammography Cohort
&
The Cohort of Swedish Men

81,922 subjects (36,616 women and 45,306 men).

6.8
(1998-2004)

135
(61 women and 74 men)

Primary malignant neoplasm of the exocrine pancreas incidence

Citrus fruits (oranges, grapefruits, orange/grapefruit juice, and other citrus fruits)

HR = 1.12 (0.68-1.83; P = 0.53) for the highest vs lowest quartile of consumption.

Amount specific data (servings/wk):
< 1.0: HR = 1.
1.0-2.9: HR = 0.88 (0.52-1.50).
3.0-6.9: HR = 1.26 (0.81-2.00).
≥ 7.0: HR = 1.12 (0.68-1.83).

Age, sex, education, BMI, physical activity, cigarette smoking status and pack-years of smoking, multivitamin supplement use, and intakes of total energy, alcohol, green leafy vegetables and cruciferous vegetables.

6) Bobe G (2008)

The Alpha-Tocopherol, beta-Carotene Cancer Prevention Study (ATBC)

27,111 healthy male smokers of ≥ 5 cigarettes/day aged 50-69.
(Finland)

16.1
(1985-2004)

306

Primary exocrine adenocarcinoma of the pancreas incidence

Citrus fruits (not defined)

HR = 1.05 (0.74-1.49; P = 0.84) for the highest vs lowest quintile of consumption.

Amount specific data (g/day):
≤ 4.43: HR = 1.
> 4.43-13.99: HR = 1.05 (0.75-1.48).
14.00-27.72: HR = 0.85 (0.59-1.22).
> 27.72-58.79: HR = 0.84 (0.58-1.20).
> 58.80: HR = 1.05 (0.74-1.49).

Effect modification:
No significant interaction was found by intervention (any supplement [alpha-tocopherol, beta-carotene, or both] vs placebo).

Age at randomization, years of smoking, total number of cigarettes per day, self-reported history of diabetes mellitus, and energy-adjusted saturated fat intake.

6) Stolzenberg-Solomon RZ (2002)

The Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study (ATBC).

27,111 male smokers of ≥ 5 cigarettes/day aged 50-69.
(Finland)

13
(1985-88 to 1997)

163?

Primary malignant neoplasm of the exocrine pancreas incidence

Citrus fruits (not defined)

HR = 0.79 (0.47-1.31; P = 0.53) for the highest vs lowest quintile of consumption.

Amount specific data (g/day):
≤ 5.3: HR = 1.
> 5.3 and ≤ 22.6: HR = 1.15 (0.73-1.82).
> 22.6 and ≤ 46.2: HR = 0.74 (0.44-1.23).
> 46.2 and ≤ 90.9: HR = 1.14 (0.72-1.81).
> 90.9: HR = 0.79 (0.47-1.31).

Energy intake, age and years of smoking.

Additional variables examined in the analyses included ATBC trial interventions; dietary folate, saturated fat, and carbohydrate intakes; history of diabetes mellitus; occupational physical activity; and education.

Men:

Women:

HR = 0.89 (0.60-1.33) for the highest vs lowest tertile of consumption.

Amount specific data:
< 3/w: HR = 1.
3-4/w: HR = 0.98 (0.65-1.46).
≥ 5/w: HR = 0.89 (0.60-1.33).

HR = 0.83 (0.58-1.19) for the highest vs lowest tertile of consumption.

Amount specific data:
< 3/w: HR = 1.
3-4/w: HR = 0.73 (0.48-1.13).
≥ 5/w: HR = 0.83 (0.58-1.19).

Stratified by gender:

Men
(100 cases)

women
(123 cases)

HR = 0.85 (0.47-1.51; P = 0.58) for the highest vs lowest tertile of consumption.

Amount specific data (Frequency of intake):
0-2/mo: HR = 1.
1-4/wk: HR = 0.88 (0.53-1.46).
Almost every day: HR = 0.85 (0.47-1.51).

HR = 1.07 (0.57-1.98; P = 0.90) for the highest vs lowest tertile of consumption.

Amount specific data (Frequency of intake):
0-2/mo: HR = 1.
1-4/wk: HR = 1.07 (0.58-1.98).
Almost every day: HR = 1.07 (0.57-1.98).

Stratified by smoking status:

Smokers
(65 cases)

Nonsmokers
(114 cases)

HR = 1.08 (0.53-2.21; P = 0.86) for the highest vs lowest tertile of consumption.

Amount specific data (Frequency of intake):
0-2/mo: HR = 1.
1-4/wk: HR = 1.20 (0.64-2.24).
Almost every day: HR = 1.08 (0.53-2.21).

HR = 0.95 (0.52-1.74; P = 0.93) for the highest vs lowest tertile of consumption.

Amount specific data (Frequency of intake):
0-2/mo: HR = 1.
1-4/wk: HR = 0.94 (0.52-1.69).
Almost every day: HR = 0.95 (0.52-1.74).

Men:

Women:

RR = 1.0 (0.8-1.2) for the highest vs lowest quartile of consumption.

Amount specific data (Quartiles not defined):
Q1: RR = 1.
Q2: RR = 0.9 (0.8-1.1).
Q3: RR = 1.0 (0.8-1.1).
Q4: RR = 1.0 (0.8-1.2).

RR = 0.9 (0.7-1.1) for the highest vs lowest quartile of consumption.

Amount specific data (Quartiles not defined):
Q1: RR = 1.
Q2: RR = 0.9 (0.8-1.1).
Q3: RR = 1.0 (0.9-1.1).
Q4: RR = 0.9 (0.7-1.1).

Cancer & Diet. A systematic review.

Literature review.

Relating various aspects of our diet
to pancreatic cancer risk & mortality.

Citrus fruit and pancreatic cancer.

Cancer & Diet. A systematic review.

Literature review.

Relating various aspects of our dietto pancreatic cancer risk & mortality.

Citrus fruit and pancreatic cancer.

Relating various aspects of our diet
to pancreatic cancer risk & mortality.