Vegetables and lung cancer.

Total vegetables and lung cancer risk.

About the male analysis: In 2003 a pooled analysis of 8 prospective studies was published (Smith-Warner SA [24]). The analysis included data from a total of 1,808 men of which 298 were from The ATBC Study. In 2002 another publication about The ATBC Study included data from 1,644 men (Holick CN [18]), which is nearly as much as the total amount of cases from the pooled analysis. A similar finding was done with The Netherlands Cohort Study. For this systematic review it was chosen not to include data about men from the pooled analysis as a whole, but from the individual cohorts, because this allowed for a much larger amount of cases in the analysis.
As a consequence of this decision, data about men from The New York State Cohort (including 392 male cases) can not be included in these specific parts of the review, since no article is published about this specific cohort.

Results:

  • Men & women combined: 32 articles, providing information about 20 different cohorts were found, including 14,125 cases. Significant protective effects were found in 3 cohorts among men (Balder HF [11], Holick CN [18], George SM [29]) including 7,162 male cases. The average RR = 0.90 (excluding incomplete data from Shekelle RB [1], and Ratnasinghe D [15]).
  • Men: Data about 11 cohorts including a total of 8,107 cases was found. A significant protective effect was found in 3 cohorts (Balder HF [11], Holick CN [18], George SM [29]) including 7,162 cases (88% of all cases). No associations were found in the remaining 8 cohorts.
    The average RR = 0.82 (excluding incomplete data from Shekelle RB [1], and Ratnasinghe D [15]).
  • Women: Data about 9 cohorts including a total of 3,863 cases was found. No significant associations were found. The average RR = 1.01
  • In three other cohorts including a total of 2,294 cases, risk was not stratified by sex. No associations were found. The average RR = 0.98

Inclusion of intermediate levels of consumption:
(Non)significant effects at any level of consumption among men were as follows:

  • Balder HF (11) At 294 g/day (highest quintile of consumption).
  • Holick CN (18) At ≥ 110 g/day.
  • George SM (29) At 170-235, and at ≥ 424 g/day (2nd and 5th quintile of consumption).

Among men, overlapping effects were found at the level of ≥ 170 g/day.

RRs for the association between total vegetables and lung cancer risk among men (g/day):


(Non)significant effects at any level of consumption among women were as follows:

  • Smith-Warner SA [24] At the 3rd quintile of consumption. No level of consumption could be defined, because the pooled analysis included study-specific quintiles of consumption from the 6 cohorts.

Among women, the possibility of an association at an intermediate level of consumption can not be excluded, but is impossible to assess based on this data.

Effect modification by variables other than sex and smoking status:
A significant protective effect among cancer cases diagnosed at age < 65 years, but not ≥ 65 years was found in a pooled analysis of 8 cohorts (Smith-Warner [24]). In the same analysis, no evidence of effect modification was found by the number of fruit and vegetable questions included on a study's FFQ.
No evidence of effect modification was found by alcohol intake or multivitamin use in two cohorts (Feskanich D [14]), or by use of beta carotene/vitamin A supplements in another cohort (Neuhouser ML [22]).

Conclusion: For men, a significant protective effect was found in 3 cohorts of moderate-very large size, and no (non)significantly increased risks were found in the remaining cohorts. Total vegetables possibly protect against lung cancer risk among men (- 18%). Levels of consumption for this effect were ≥ 170 g/day, and the effect may be restricted to cancer cases diagnosed at age < 65 years. No associations were found among women.

Prospective studies of total vegetables and lung cancer risk (men):
AuthorCohort nameCasesRelative Risk (RR)
29) George SM (2008)The NIH-AARP Diet and Health Study4,092RR = 0.87 (0.78-0.96; P = 0.024)
27) Alavanja MC (2004)The Agricultural Health Study206RR = 0.8 (0.5-1.2; P = 0.13)
18) Holick CN (2002)The ATBC Study1,644RR = 0.75 (0.63-0.88; P = < 0.001)
15) Ratnasinghe D (2000)No cohort name106No significant difference (P = 0.46)
14) Feskanich D (2000)The Health Professionals' Follow-up Study258RR = 1.04 (0.69-1.57)
11) Balder HF (2005)The Netherlands Cohort Study1,426RR = 0.66 (0.50-0.87; P = 0.008)
8) Knekt P (1999)The Finnish Mobile Clinic Health Cohort138RR = 0.83 (0.54-1.26)
5) Jansen MC (2004)The Zutphen Elderly Study42RR = 0.95 (0.44-2.07; P = 0.92)
4) Shibata A (1992)The Leisure World Study94RR = 1.37 (0.74-2.25)
2) Kvale G (1983)No cohort name68RO = 0.74 (P = 0.37)
1) Shekelle RB (1981)The Western Electric Study33A nonsignificant inverse association (P = 0.23)
Total number of cases: 8,107Average RR = 0.82


Prospective studies of total vegetables and lung cancer risk (women):
AuthorCohort nameCasesRelative Risk (RR)
29) George SM (2008)The NIH-AARP Diet and Health Study2,347RR = 1.08 (0.94-1.23; P = 0.219)
27) Alavanja MC (2004)The Agricultural Health Study48RR = 0.6 (0.2-1.7; P = 0.09)
24) Smith-Warner SA (2003)Pooled analysis of 6 studies1,398RR = 0.93 (0.78-1.12; P = 0.59)
4) Shibata A (1992)The Leisure World Study70RR = 0.58 (0.32-1.05)
Total number of cases: 3,863Average RR = 1.01


Prospective studies of total vegetables and lung cancer risk (not stratified by sex):
AuthorCohort nameCasesRelative Risk (RR)
25) Liu Y (2004)The JPHC Study428RR = 1.03 (0.81-1.30)
22) Neuhouser ML (2003)The CARET Study326 (placebo), and
414 (intervention)
Placebo arm: RR = 0.82 (0.59-1.14; P = 0.39).

Intervention arm: RR = 0.81 (0.65-1.21; P = 0.46).
19) Linseinen J (2007)The EPIC Study1,126HR = 1.06 (0.83-1.36)
Total number of cases: 2,294Average RR = 0.98

Total vegetables and lung cancer risk. Stratified by smoking status.

Background:
About the analysis: For this systematic review, data is stratified by smoking status into current smokers, former smokers, and never smokers.
The JPHC Study (Liu Y [25]) and CARET Study (Neuhouser M [22]) provided data about "ever smokers" without stratifying into former vs current smokers. Likewise, The Finnish Mobile clinic Health Cohort (Knekt P [8]) provided data about "current nonsmokers" without stratifying into nonsmokers vs former smokers. It was chosen not to include this data in the following tables.
About the analysis of current smokers: In 2003 a pooled analysis of 8 prospective studies was published (Smith-Warner SA [24]). The analysis included data from a total of 1,915 smoking cases of which 298 were from The ATBC Study. In 2002 another publication about The ATBC Study included data from 1,644 smoking cases (Holick CN [18]), which is nearly as much as the total amount of cases from the pooled analysis. For the systematic review it was chosen not to include data about current smokers from the pooled analysis as a whole, but from the individual cohorts, because this allowed for a much larger amount of cases in the analysis.

Results:

  • Current smokers: Data about current smokers was provided by 8 cohorts, including 6,206 cases. Significant protective effects were found in 3 cohorts (Voorrips LE [11]), Feskanich D [14] among women, and Holick CN [18]), including 2,436 cases (39% of all cases). And a nonsignificant protective effect was found in a fourth cohort (Steinmetz KA [10]). No other (non)significant associations were found. The average RR = 0.85
  • Former smokers: Data about former smokers was provided by a pooled analysis of 7 cohorts, and 2 additional cohorts which were both of very large size. The analysis included 4,217 cases. A significant protective effects was found in one cohort among men, while among women a nonsignificantly increased risk was found (Wright ME [29]). No other associations were found. The average RR = 1.01
  • Never smokers: Data about never smokers was provided by a pooled analysis of 7 cohorts, and 3 additional cohorts, including 774 cases. No (non)significant effects were found. The average RR = 0.94

Conclusion: Significant protective effects among current smokers were found in 3 cohorts of moderate-large size, including 39% of all cases. Suggestive evidence was found for a protective effect of total vegetables against lung cancer risk among current smokers (- 15%). Few associations were found among former-, or never smokers, and no evidence was found for an association among these subgroups.

Prospective studies of total vegetables and lung cancer risk (current smokers):
AuthorCohort nameCasesRelative Risk (RR)
29) Wright ME (2008)The NIH-AARP Diet and Health Study1,583 men, and
1,196 women
Men: RR = 0.97 (0.81-1.16; P = 0.90).

Women: RR = 1.01 (0.84-1.22; P = 0.75).
19) Linheisen J (2007)The EPIC Study731HR = 0.78 (0.54-1.13)
18) Holick CN (2002)The ATBC Study1,644RR = 0.75 (0.63-0.88; P = < 0.001).
14) Feskanich D (2000)The Nurses' Health Study

&

The Health Professionals' Follow-up Study
86 men, and

269 women
Men: RR = 0.95 (0.45-2.03)..

Women: RR = 0.59 (0.39-0.89).
11) Voorrips LE (2000)The Netherlands Cohort Study523RR = 0.7 (0.5-1.0; P = 0.003).
10) Steinmetz KA (1993)The Iowa Women's Health Study81OR = 0.63 (0.30-1.33; P = 0.08).
8) Knekt P (1991)The Finnish Mobile Clinic Health Cohort93RR = 0.98 (P = 0.81) for low vs high consumption.
Total number of cases: 6,206Average RR = 0.85


Prospective studies of total vegetables and lung cancer risk (former smokers):
AuthorCohort nameCasesRelative Risk (RR)
29) Wright ME (2008)The NIH-AARP Diet and Health Study2,110 men, and
835 women
Men: RR = 0.88 (0.77-1.01; P = 0.01).

Women: RR = 1.26 (1.01-1.58; P = 0.07).
24) Smith-Warner SA (2003)Pooled analysis of 7 studies981RR = 0.97 (0.76-1.24; P = 0.83)
19) Linheisen J (2007)The EPIC Study291HR = 1.33 (0.85-2.08)
Total number of cases: 4,217Average RR = 1.01


Prospective studies of total vegetables and lung cancer risk (never smokers):
AuthorCohort nameCasesRelative Risk (RR)
29) Wright ME (2008)The NIH-AARP Diet and Health Study141 men, and
170 women
Men: RR = 0.94 (0.56-1.59; P = 0.99).

Women: RR = 0.72 (0.42-1.22; P = 0.27).
25) Liu Y (2004)The JPHC Study106RR = 1.37 (0.79-2.37; P = 0.20)
24) Smith-Warner SA (2003)Pooled analysis of 7 studies259RR = 0.90 (0.58-1.40; P = 0.75)
19) Linheisen J (2007)The EPIC Study98HR = 0.97 (0.46-2.04)
Total number of cases: 774Average RR = 0.94

Total vegetables and lung cancer mortality.

Data about lung cancer mortality is provided by 4 cohorts. Three of these cohorts measured food intake prior to cancer diagnosis (5, 9, 16), and another one following diagnosis (19). No associations were found. The average RR = 1.02 (excluding incomplete data from Skuladottir H [19]).

Conclusion: No associations were found. No evidence was found for an association between total vegetables and lung cancer mortality.

Prospective studies of total vegetables and lung cancer mortality:
AuthorCohort nameCasesRelative Risk (RR)
19) Skuladottir H (2006)The Danish Diet, Cancer and Health StudyNot definedHR = 0.84 (0.59-1.21)
16) Breslow RA (2000)The NIHS158RR = 0.9 (0.5-1.5; P = 0.786)
9) Chow WH (1992)The Lutheran Brotherhood Cohort219RR = 1.2 (0.6-2.3)
5) Jansen MC (2001)The Seven Countries Study149RR = 0.90 (0.61-1.33; P = 0.59)
Total number of cases: 526 + XAverage RR = 1.02