Citrus fruit and lung cancer.
Lung cancer risk: Data about lung cancer risk was provided by 9 cohorts including a total of 10,704 cases. Significant protective effects of high vs low
consumption were found in one cohort examining men + women (11), and in two other cohorts examining women only (10, 14) including a total of 2,126 cases (20% of all cases).
No other associations were found. The average RR = 0.90 (excluding incomplete data from Liu Y [25]).
Results for men: Data about men only was provided by 2 cohorts (14, 29), incuding 4,092 cases. No associations were found. The average RR = 1.00.
Results for women: Data about women only was provided by 3 cohorts (10, 14, 29), including 3,477 cases. Significant protective effects were found in one cohort (14),
and in a second cohort among ever smokers (10), including 1,163 cases (33% of all cases). The average RR = 0.86.
When extreme categories of consumption were considered, the effects size became stronger and significant in one of the cohorts (RR = 0.91 to 0.80 for Wright ME [29]).
As a result, the average RR became: 0.79.
| Author | Cohort name | Cases | Relative Risk (RR) |
|---|---|---|---|
| 29) Wright ME (2008) | The NIH-AARP Diet and Health Study | 3,834 men, and 2,201 women | Men: RR = 0.99 (0.89-1.10; P = 0.68). Women: RR = 0.91 (0.79-1.04; P = 0.55). |
| 25) Liu Y (2004) | The JPHC Study | 251 | No association. |
| 22) Neuhouser ML (2003) | The CARET | 326 placebo, and 414 intervention | Placebo arm: RR = 0.72 (0.46-1.10; P = 0.15). Intervention arm: RR = 0.84 (0.58-1.21; P = 0.22). |
| 19) Linseisen J (2007) | The EPIC Study | 1,126 | HR = 0.87 (0.70-1.07). |
| 14) Feskanich D (2000) | The Health Professional's Follow-up Study & The Nurses' Health Study | 258 men, and 516 women | Men: RR = 1.12 (0.77-1.61). Women: RR = 0.72 (0.54-0.97). |
| 11) Voorrips LE (2000) | The Netherlands Cohort Study | 963 | RR = 0.8 (0.6-1.1; P = 0.01). |
| 10) Cutler GJ (2008) | The Iowa Women's Health Study | 113 never smokers, and 647 ever smokers | Never smokers: RR = 1.12 (0.70-1.76; P = 0.61). Ever smokers: RR = 0.73 (0.60-0.89; P = 0.01). |
| 7) Fraser GE (1991) | The Adventist Health Study | 55 | RR = 0.64 (0.35-1.17). |
| Total number of cases: 10,704 | Average RR = 0.90 |
Inclusion of intermediate levels of consumption:
The figure below includes RRs for the association between citrus fruit and lung cancer risk among women. Significant protective effects were found of high vs
low consumption in 2 cohorts (Cutler GJ among ever smokers at ≥ 4 servings/wk; and Feskanich D at > 9 servings/wk), and at an intermediate
level of consumption in the remaining cohort (Wright ME at 7 servings/wk).
Effect modification: Inconsistent findings were done among current- (11, 19, 29), and never smokers (10, 19, 29). But a consistent lack of an association
was found among past smokers (11, 19, 29).
Lung cancer mortality: Data about lung cancer mortality was provided by 3 cohorts. Significant protective effects were found among men in 2 cohorts (5, 17),
while no association was found among women (17). The level of consumption for this effect could not be defined, because no definitions of units of consumption were
given in the smaller cohort. The average RR = 0.76.
Conclusion: Among women, significant protective effects of high vs low consumption were found in 2 cohorts of moderate-large size. In addition, a significant
protective effect was found in one cohort of very large size at an intermediate level of consumption. Among women, citrus fruit possibly protects against lung
cancer risk (- 14%). This effect was found a at a median level of consumption (7 servings/wk), and suggestive evidence was found for a protective effect at > 9 servings/wk.
No consistent evidence was found for effect modification, but no evidence was found for an association among past smokers.
Significant protective effects against lung cancer mortality were found among men in 2 cohorts, one of which was of very small size. Suggestive evidence
was found for a protective effect of citrus fruit against lung cancer mortality among men (- 24%). No level of consumption could be defined for this effect.
| Author | Cohort name | Subjects | Years of follow-up | Cases | End point | Consumption of | Relative Risk (RR) | Adjustments | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 29) Wright ME (2008) | The NIH-AARP Diet and Health Study | 472,081 subjects (281,288 men and 190,793 women) aged 50-71. (USA) | 8 (1995-2003) | See variables | Lung cancer risk | Rutaceae (oranges, tangerines, tangelos, and grapefruits) |
All men (3,834 cases): RR = 0.99 (0.89-1.10; P = 0.68) for the highest vs lowest quintile of consumption. Amount specific data (servings per 1000 kcal per day): 0.04: RR = 1. 0.19: RR = 0.99 (0.91-1.09). 0.43: RR = 0.97 (0.88-1.07). 0.73: RR = 0.95 (0.86-1.05). 1.35: RR = 0.99 (0.89-1.10).
All women (2,201 cases): RR = 0.91 (0.79-1.04; P = 0.55) for the highest vs lowest quintile of consumption. Amount specific data (servings per 1000 kcal per day): 0.05: RR = 1. 0.21: RR = 0.90 (0.79-1.01). 0.50: RR = 0.86 (0.75-0.98). 0.84: RR = 1.00 (0.88-1.13). 1.51: RR = 0.91 (0.79-1.04). An inverse association emerged among women in the top decile of citrus fruits intake (RR = 0.80; 95% CI = 0.66-0.97; P = 0.28). for consumption > 1.51 servings per 1,000 calories/day. In analyses stratified by histological type, a notable inverse association was observed between squamous cell carcinoma and intakes of citrus fruits (RR = 0.65; 95% CI = 0.45-0.96; P = 0.04).
One serving of fruits = 1 medium sized fresh fruit, 1/2 cup of chopped fruit, or 6 ounces of fruit juice. Age, energy intake, race, education, BMI, smoking status, smoking dose, time since quitting, alcohol intake, physical activity, and family history of any cancer. |
25) Liu Y (2004) | Cohort II of The JPHC Study | 51,114 (aged 40-69) subjects. | (Japan) 7 | (1993-1999) 251? | lung cancer risk | citrus | Inverse associations between lung cancer and specific individual fruits were not observed (no data shown). | age, gender, area, sports, frequency of alcohol intake, BMI, vitamin supplement use, salted fish and meat, pickled vegetables, smoking duration, and number of cigarettes per day among ever smokers. |
22) Neuhouser ML (2003) | The Beta-carotene And Retinol Efficacy Trial (CARET) (2003) | 14,120 current or former heavy smokers (male/female) and asbestos-exposted workers (male) aged 50-69. | 12 | (1989-2001) 742? | (326 in placebo arm, and 414 in intervention arm) Primary lung cancer risk | Rutaceae (oranges, grapefruit, orange juice, and grapefruit juice) |
|
Sex, age, smoking status, total pack-years of smoking, asbestos exposure, race-ethnicity, enrollment center, and total fruit. |
19) Linseisen J (2007) | The EPIC Study | 478,590 individuals, mostly aged 25-70 from 10 European countries. | 6.4 | (1992-2000) 1,126 (608 men, 518 women), of which 731 current smokers, 291 former smokers, and 98 never smokers) | lung cancer risk | Citrus fruits |
HR = 0.87 (0.70-1.07) for the highest vs lowest quintile of consumption. | Amount specific data (g/day): 0-5.9: HR = 1. 5.9-16.6: HR = 0.92 (0.78-1.08). 16.6-41.7: HR = 0.82 (0.67-0.996). 41.7-82.9: HR = 0.86 (0.71-1.04). 82.9-2487.2: HR = 0.87 (0.70-1.07).
Since results were not significantly different between men and women, no sex-stratified results are presented. adjusted for tobacco smoking (status and duration), education (5 categories), physical activity at work (5 categories), intake of red meat, intake of processed meat, height, weight, nonfat energy intake, energy intake from fat, ethanol intake at baseline |
14) Feskanich D (2000) | The Nurses' Health Study | & The Health Professionals' Follow-up Study 77,283 US women (38-63 years) and 47,778 men (40-75 years) | Women: 1984-1996. | Men: 1986-1996. 516? women, and | 258? men Total lung cancer risk | Citrus fruits (include oranges, orange juice, grapefruit, and grapefruit juice) |
|
age, follow-up cycle, smoking status,years since quitting among past smokers, cigarettes smoked/day among current smokers, age at start of smoking, total energy intake, and availability of diet data after baseline measure |
11) Voorrips LE (2000) | The Netherlands Cohort Study | 62,573 women and 58,279 men aged 55-69. | 6.3 | (1986-1992) 963 | lung cancer risk | Citrus fruit (mandarins, oranges and fresh orange juice, grapefruits and fresh grapefruit juice, processed orange/grapefruit juice) |
RR = 0.8 (0.6-1.1; P = 0.01) for the highest vs lowest quintile of consumption. | Amount specific data (g/day): 3: RR = 1. 28: RR = 0.7 (0.6-1.0). 62: RR = 0.7 (0.5-0.9). 100: RR = 0.7 (0.5-1.0). 175: RR = 0.8 (0.6-1.1). Additional adjustment for total vegetable intake did not change results at all (No data shown). An inverse association among current, but not in former smokers was found (no data shown). age, sex, family history of lung cancer, highest educational level, current smoker, years of smoking, number of cigarettes/day and total fruit intake. |
10) Cutler GJ. (2008) | The Iowa Women's Health Study. | 34,708 postmenopausal women aged 55-69. | (USA) 1986-2004 | 760 (113 never smokers, and 647 ever smokers) | Lung cancer risk | Citrus fruit or juice (grapefruits, grapefruit juice, oranges, orange juice) |
|
Age, energy, education, race, BMI, multivitamin use, activity level, and pack years. |
7) Fraser GE (1991) | The Adventist Health Study | 34,198 white California seventh-day adventists. | (USA) 6 | (1977-1982) 55 | Lung cancer risk | Fresh citrus fruit (not defined) | RR = 0.64 (0.35-1.17; No P-value) for consumption ≥ 3 vs < 3 times/wk. | Age, sex, and smoking history |
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