We found no statistically significant association between red or processed meat and lung cancer in the participants of the PLCO trial. Meat cooking methods and the level of doneness, as well as investigated mutagens and heme iron intake from meat, had no statistically significant effect on lung cancer risk.
In a recent analysis of 6,800 cases in another prospective U.S. study that used the same dietary questionnaire and meat mutagens database as this study, red and processed meat were positively associated with lung cancer in men and there was a suggestive positive association for women19
. We, however, had much less cases (N = 782 cases). In addition, our participants were more educated and were more likely to be never smokers than the AARP participants19
, although we carefully adjusted for both education and smoking. The evidence from other cohorts is also inconsistent31–35
and difficult to compare; cohorts used different definitions to identify meat exposures and different cut-points to categorize intake, employed dietary patterns rather than a single food approach to study the exposure effect31
, studied relatively younger cohorts35
or investigated mortality rather than morbidity of lung cancer as an outcome32–34
. Furthermore, some studies were conducted in countries with smoking and dietary habits different from the U.S.31, 33–35
High temperature cooking methods and doneness of meat have been used as a surrogate measure for HCAs and PAHs exposures36
. In our analysis, meat doneness level was not statistically significantly associated with lung cancer. In the NIH-AARP cohort, the risk increased with consumption of well/very-well done meat in men, whereas in women consuming rare meat was inversely associated with risk19
. Higher risk with well-done meat intake was also observed in a case-control study of 1,216 non-smoking women who provided detailed dietary information on meat cooking preferences17
. Furthermore, this study also found a borderline statistically significant increase in risk for lung cancer for fried and broiled red meat17
, in contrast to our study where no statistically significant association was found with any of the cooking methods. We found a borderline significant decrease in risk in women with B(a)P intake >11.9 ng/1000 kcal compared to those with intake 0.9 ng/1000 kcal or less. Contrary to our finding, Lam et al18
reported 1.3 fold increase in risk in participants in the highest (≥85.4 ng/d) vs. lowest tertile of B(a)P intake (<0.2 ng/d) in a population-based case-control study from Italy. The range of B(a)P intake in our participants was, however, evidently narrower compared to one reported by Lam et al18
, from their Italian population, where a great variety of processed meats are commonly consumed. They also found an increased risk with higher intake of MeIQx, PhIP and overall mutagenic activity. Two other studies observed elevated lung cancer risk with higher MeIQx intake; one in women16
and in one, risk was apparent only in men19
. Given that the former study was done in non-smoking women only16
, it may be that the effect of smoking is so large that small effects of diet are more likely to become apparent in non-smokers. Furthermore, a narrower intake range across meat mutagens compared to Sinha et al16
could have been a reason for null association in our cohort.
In our participants, heme iron intake was not statistically significantly associated with lung cancer risk. In a case-control study, Zhou et al37
observed a positive association between total iron and lung cancer, which was due to non-heme iron, whereas heme-iron was found to be protective. Contrary to these findings, two cohorts19, 38
observed increased risk with high heme iron intake, which became even more pronounced in participants with diet poor with fruit and vegetable intake19
or in former and current smokers taking vitamin C supplements38
. However, with the exception of the AARP cohort19
, none of the previous studies have estimated heme iron intake based on a specific database with measured values.
Investigation of the effect of meat by histological sub-type of lung cancer showed that similarly to our study, two studies found no difference in associations among different histological types39, 40
. One study detected an increased risk for non-adenocarcinoma cell tumors31
. in another study, risk was increased for all histological types, but was strongest for adenocarcinoma41
, whereas two studies detected an increased risk for squamous cell carcinoma42, 43
. Lam et al18
observed an elevated risk for both squamous and adenocarcinomas of the lung, whereas the NIH-AARP study detected an increased risk for squamous carcinoma in men and small cell carcinoma in women, although the risk between histological types was not statistically different19
While we carefully controlled for multiple smoking characteristics, we lacked information on passive smoking, types of cigarettes smoked and depth of inhalation, which might have limited our ability to fully control for this powerful confounder. Thus, we acknowledge that even the modest non-significant effect of red and processed meat we are seeing may be due to residual confounding by smoking, given its strong effect. Nevertheless, we found no correlation between any of the smoking characteristics, and red or processed meat intake.
Only fruit and total fat intake were correlated with meat consumption in our analysis, however, neither of the two exposures was associated with lung cancer (data not shown). The fat content of meat has been postulated as one of the potential mechanisms relating meat to lung carcinogenesis, yet a pooled analysis of eight prospective studies observed no association of total fat, or any of the specific types of fat, with lung cancer risk44
The prospective design of the PLCO trial, with diet being assessed prior cancer diagnosis, avoided the effect of recall or selection bias. To further limit the effect of reverse causality, we excluded all cases diagnosed within the first year of follow-up. Detailed information on meat cooking practicies, and the meat mutagen database allowed us to investigate different possible mechanisms for the effect of meat on lung cancer. However, we lacked information on B(a)P exposure from other dietary sources, which may be considerable45
. FFQs are known to have substantial measurement error that can lead to bias in estimated diet-disease risks and, in multivariable models can lead to distorted confidence intervals. The measurement error related to the meat mutagen database is also likely to have caused further attenuation of the risk estimates. In addition, a narrow range of intake of high temperature cooked meats may have affected our ability to detect an association. On average, only approximately 20% of meats consumed in our cohort were meats cooked at high temperature. Participants enrolled in the PLCO trial were found to be better educated, more physically active, more likely to be married, less likely to smoke, and had lower all-cause and cause-specific standardized mortality than the general population46
. They were also recruited among volunteers, hence it is reasonable to expect that they may have had healthier dietary behaviors. The FFQ was administered up to 4 years after baseline, at which time point no updates on participants’ baseline characteristics were collected; some of those might have changed, therefore causing residual confounding in our analyses. The follow-up period in our cohort was relatively shorter compared to other cohorts19, 31, 32, 33, 34, 35
, which certainly affected the statistical power of this analysis.
In conclusion, consumption of a diet high in red or processed meat was not associated with lung cancer in our population. We observed no effect of high temperature cooking methods, level of meat doneness, intake of meat mutagen or heme iron on risk of lung cancer.