In this cohort a clear association between vegetarianism (as a single category) and all cancers, was found. This association was clearest in the vegan diet, where there was a mild protection for overall cancer risk. When dividing cancers to anatomical site or gender-specific groupings some statistically significant associations were also found. Specifically vegetarians had less gastro-intestinal cancer (HR=0.76), especially among lacto-ovo vegetarians (HR=0.75). In addition, vegan women experienced fewer female-specific cancers (HR=0.66). It is also noteworthy that, although often not statistically significant, the great majority of hazard ratio point estimates for effects of vegetarian status or its sub-types are less than 1.0. Exceptions are only male semi-vegetarians (), lacto and semi-vegetarians in female-specific cancers and urinary tract cancers (). When adding BMI into the multivariate models most of the statistically relative risks remain significant, but move slightly toward the null suggesting that BMI may be one mediator of the dietary effects.
Few prospective studies have looked at associations between vegetarian diets and cancer risk.(8
) Among the Seventh-day Adventist population, cancer risk for all sites combined (20
) has been previously reported as lower than an external reference population. Since many Adventists do not consume meat regularly, it is possible that low meat consumption, or the replacement sources of energy for the meat, would confer this protection. Furthermore, when exploring dietary associations with the risk of specific cancers, analyses in the older AHS-1 cohort data found evidence that meat consumption is directly associated with the risk of specific cancer-sites and also that greater consumption of vegetables and fruits predicts lower risk of certain cancer sites.(21
) Further evidence comes from the pooled analysis of data from two prospective studies in the United Kingdom, namely the Oxford Vegetarian Study and, the European Prospective Investigation into Cancer and Nutrition-Oxford (EPIC-Oxford) cohort where 12% decreased risk of overall cancer was observed among vegetarians compared to meat eaters after adjustment for potential confounding factors.(8
) However, associations between the vegan diet and cancer were not evaluated separately because of the small number of cancers reported.
A link has been suggested between specific plant foods such as fruits and vegetables, plant constituents such as fiber, antioxidants, other phytochemicals, maintaining a healthy weight, and a lower incidence of cancer.(22
) Vegetarians and vegans generally include greater amounts of plant foods, avoid the intake of meat, and often adopt other healthy lifestyles compared to non-vegetarians.(12
) Thus there is reason to suspect that vegetarian diets may protect against cancer. Factors associated with the high fiber content in vegetarian diets promote increased insulin sensitivity.(23
) A cross-sectional study suggests, in addition, that a plant-based diet is associated with lower circulating levels of total IGF-I and higher levels of IGFBP-I and IGFBP-2 compared with a meat-eating or even a lacto-ovo-vegetarian diet.(24
) Insulin and IGF-I act as promoters for most normal and pre-neoplastic tissues. Therefore, their down- regulation may reduce cancer rates.(25
In our study, an inverse association was evident between vegan diets and female-specific cancers. Much of the known epidemiology of gynecologic and breast cancers can be explained by hormonal factors, and the only definite lifestyle effects on risks of these cancers are obesity, physical activity, and alcohol consumption.(28
) Vegan diets conceivably protect against cancers linked to obesity, elevated IGF-1 levels, and insulin resistance.(25
) As there is evidence that obesity is a risk factor for several common female-specific cancers (29
) and that high levels of IGF-I may also increase the risk of some female-specific cancers (30
), these are potentially protective pathways.
Vegans also consume substantial amounts of soybeans or foods made from soy beans. Soy foods are rich in phytoestrogens which have been hypothesized to reduce breast cancer risk.(28
) Finally, the low intake of protein and the lower frequency of obesity in this group, suggests a lower energy intake that may well delay the onset of menarche and also influence hormone status at other periods of life. (33
Our results suggest that lacto-ovo-vegetarians compared to meat eaters are inversely associated with the development of cancers of the gastrointestinal system. Previous studies have strongly suggested that dairy foods are inversely associated with cancers of the digestive system in both men and women,(5
) this being especially so for colorectal cancer.(5
) Similar effects for gastric (37
) and pancreatic(40
) cancer are either controversial or absent. It is important to note that in those studies with null or positive (rather than negative) associations, high fat dairy products were generally the main exposures of interest. Calcium has been shown to reduce proliferation, stimulate differentiation, and induce apoptosis in cells of the gastrointestinal tract.(41
No statistically significant associations between dietary patterns and cancers of the respiratory tract, urinary tract and male cancers were observed. However, the point estimates, particularly in the pesco-vegetarian group, were in the protective direction for cancers of the respiratory and urinary system. Key and colleagues have reported similar inverse non-statistically significant associations between fish eaters and lung, kidney and bladder cancer incidence.(8
) Further investigation is necessary with larger numbers in the future and also when considering specific cancers.
The major strength of our study is its prospective design and the validation of new cancers through cancer registries. Also, the unique lifestyle of the Adventist population with a wide variety of dietary habits, a very low percentage of alcohol consumption or cigarette smoking, reduces the possibility of confounding by these non-dietary factors.
The potential limitations of our study include unavoidable inaccuracies in the assessment of food consumption. It is likely that participants may have overestimated some foods generally considered beneficial due to social desirability. However, this type of misclassification should be non-differential, usually biasing the results toward the null. Further our published data(14
) comparing questionnaire with six 24-hour dietary recall data suggests good validity for the foods used to determine the vegetarian categories.
The non-vegetarian reference group in AHS-2 was relatively low meat-consuming. Thus, if diets mainly based on animal products provide an adverse effect it is possible that the relatively low animal product intake of the non-vegetarians in this cohort could result in smaller observed effects. Low numbers, as yet, for pesco-vegetarians, semi-vegetarians, and vegans, limit our conclusions. Finally, although we did adjust for many potential risk factors available in our study for site-specific cancer, residual confounding by unknown or unmeasured risk factors may exist for some cancers.
In conclusion, this study suggests that vegan diets may be associated with a decrease in the incidence of all cancers combined, and specifically the risk of female-specific cancers when compared with non-vegetarians. Vegetarians (mainly lacto-ovo-vegetarians) as a combined group have lower risk of all cancers and gastrointestinal cancers than meat-eaters.