Weight Cycling and Cancer Incidence
Weight Cycling and Cancer Incidence
This study is the first to comprehensively investigate the associations of weight cycling with overall and site-specific cancer risk in men and women. Results of this large prospective study showed that weight cycling was not associated with overall cancer risk or risk of 15 specific cancers independent of BMI in men or in women.
Our null findings agree with the results of some, but not all, previous studies of weight cycling and risk of specific cancers. Two factors that likely contribute to inconsistencies across studies include variability in how body size was accounted for in statistical models and differences in how weight cycling was defined. The importance of adjusting for BMI can be seen by comparing our results for all cancers, endometrial cancer, and renal cancer in women before and after this adjustment (Figure 2 and Web Table 2 http://aje.oxfordjournals.org/content/182/5/394/suppl/DC1). In these analyses, weight cycling was statistically significantly associated with increased risk before adjustment for BMI but not afterwards. Potential confounding by BMI was not considered in the case-control study that found that weight cycling was associated with a statistically significantly 2.1-fold higher risk of breast cancer. Body size was adjusted for somewhat differently by 2 of the other case-control studies that reported significant results. Although BMI as a continuous variable was used in our study, Trentham-Dietz et al. used quartiles of BMI and Luo et al. used the waist-to-hip ratio in their analyses of the associations of weight cycling and risk of endometrial or renal cancer, respectively. It is possible that residual confounding might account for the positive findings in these studies.
The lack of a standardized definition of weight cycling has led to considerable variability in the classification of weight cyclers among studies. The intentionality of the weight loss is particularly important to consider because unintentional weight loss occurs with some unhealthy behaviors such as smoking and is also an early symptom of many diseases, including several cancers. Therefore, it may be strongly related to the disease or mortality endpoint. Thus, only intentional weight loss should be considered when defining weight cyclers. However, many studies defined weight cyclers on the basis of weight patterns or variability over time, regardless of intentionality. Such studies have reported significant associations for breast and renal cancer. Other features of the weight cycling criteria that often differ between studies are the magnitude of the weight cycle and the period over which the weight cycling occurred. In the case-control study that found a significant association between weight cycling and risk of renal cancer in women but not men, a weight cycle was defined as 3 or more instances of intentional weight loss of >5 kg for women and >10 kg for men. Lindblad et al. suggest that this difference may account for their disparate findings by sex. However, we defined a weight cycle as ≥10 pounds, which was similar to the >5 kg criteria for women, and our results in both men and women were null. Whether consideration of weight cycles of a larger magnitude would alter our findings is not known.
The possibility that the association between weight cycling and endometrial cancer risk might differ by obesity status was suggested by an Australian case-control study that found no association among never-obese women and a statistically significant 2.8-fold higher risk among ever-obese women. In our study, there were modest, but not statistically significant, differences between never-obese and ever-obese women and men for some cancers, including endometrial cancer. Whereas 90% of the weight cycling cases in the Australian case-control study fell into the ever-obese category, only 45% of the endometrial cancer cases in our study were ever obese. Thus, it is possible that our ability to detect an association may have been limited by the number of ever-obese individuals. Further research in populations with more obese subjects is needed to better understand the association between weight cycling and cancer risk in this group.
To our knowledge, this study is the largest and most comprehensive study of weight cycling and cancer risk conducted to date. The size of the study and the large number of weight cyclers enabled the examination of dose-response relationships. Other strengths include the prospective nature of the study and the availability of information about important covariates, which were needed to separate the influence of these factors on cancer risk from those of weight cycling.
An important limitation to this study was the lack of information on when during adulthood the weight cycling occurred. Also absent was information on the magnitude of the weight cycling or information on weight cycles of more than 10 pounds. Thus, we were unable to assess whether specific exposure periods or amplitude of gain/loss was associated with cancer risk. An additional limitation was the number of ever-obese individuals, which limited the power of our analyses in this group. Small sample sizes in analyses stratified by either obesity or age for some of the rarer cancers also limit our ability to determine whether our null results reflect a true lack of association or difference between associations. The limited number of esophageal cancer cases also precluded investigation of subtypes of this cancer. Finally, because weight cycling was self-reported, there may be some misclassification due to incorrect responses.
In summary, the results of this study indicate that weight cycling, independent of BMI, is not associated with overall cancer risk or risk of any specific cancer in either men or women. Therefore, overweight and obese individuals should be encouraged to attempt to lose weight even though the weight lost may be regained.
Discussion
This study is the first to comprehensively investigate the associations of weight cycling with overall and site-specific cancer risk in men and women. Results of this large prospective study showed that weight cycling was not associated with overall cancer risk or risk of 15 specific cancers independent of BMI in men or in women.
Our null findings agree with the results of some, but not all, previous studies of weight cycling and risk of specific cancers. Two factors that likely contribute to inconsistencies across studies include variability in how body size was accounted for in statistical models and differences in how weight cycling was defined. The importance of adjusting for BMI can be seen by comparing our results for all cancers, endometrial cancer, and renal cancer in women before and after this adjustment (Figure 2 and Web Table 2 http://aje.oxfordjournals.org/content/182/5/394/suppl/DC1). In these analyses, weight cycling was statistically significantly associated with increased risk before adjustment for BMI but not afterwards. Potential confounding by BMI was not considered in the case-control study that found that weight cycling was associated with a statistically significantly 2.1-fold higher risk of breast cancer. Body size was adjusted for somewhat differently by 2 of the other case-control studies that reported significant results. Although BMI as a continuous variable was used in our study, Trentham-Dietz et al. used quartiles of BMI and Luo et al. used the waist-to-hip ratio in their analyses of the associations of weight cycling and risk of endometrial or renal cancer, respectively. It is possible that residual confounding might account for the positive findings in these studies.
The lack of a standardized definition of weight cycling has led to considerable variability in the classification of weight cyclers among studies. The intentionality of the weight loss is particularly important to consider because unintentional weight loss occurs with some unhealthy behaviors such as smoking and is also an early symptom of many diseases, including several cancers. Therefore, it may be strongly related to the disease or mortality endpoint. Thus, only intentional weight loss should be considered when defining weight cyclers. However, many studies defined weight cyclers on the basis of weight patterns or variability over time, regardless of intentionality. Such studies have reported significant associations for breast and renal cancer. Other features of the weight cycling criteria that often differ between studies are the magnitude of the weight cycle and the period over which the weight cycling occurred. In the case-control study that found a significant association between weight cycling and risk of renal cancer in women but not men, a weight cycle was defined as 3 or more instances of intentional weight loss of >5 kg for women and >10 kg for men. Lindblad et al. suggest that this difference may account for their disparate findings by sex. However, we defined a weight cycle as ≥10 pounds, which was similar to the >5 kg criteria for women, and our results in both men and women were null. Whether consideration of weight cycles of a larger magnitude would alter our findings is not known.
The possibility that the association between weight cycling and endometrial cancer risk might differ by obesity status was suggested by an Australian case-control study that found no association among never-obese women and a statistically significant 2.8-fold higher risk among ever-obese women. In our study, there were modest, but not statistically significant, differences between never-obese and ever-obese women and men for some cancers, including endometrial cancer. Whereas 90% of the weight cycling cases in the Australian case-control study fell into the ever-obese category, only 45% of the endometrial cancer cases in our study were ever obese. Thus, it is possible that our ability to detect an association may have been limited by the number of ever-obese individuals. Further research in populations with more obese subjects is needed to better understand the association between weight cycling and cancer risk in this group.
To our knowledge, this study is the largest and most comprehensive study of weight cycling and cancer risk conducted to date. The size of the study and the large number of weight cyclers enabled the examination of dose-response relationships. Other strengths include the prospective nature of the study and the availability of information about important covariates, which were needed to separate the influence of these factors on cancer risk from those of weight cycling.
An important limitation to this study was the lack of information on when during adulthood the weight cycling occurred. Also absent was information on the magnitude of the weight cycling or information on weight cycles of more than 10 pounds. Thus, we were unable to assess whether specific exposure periods or amplitude of gain/loss was associated with cancer risk. An additional limitation was the number of ever-obese individuals, which limited the power of our analyses in this group. Small sample sizes in analyses stratified by either obesity or age for some of the rarer cancers also limit our ability to determine whether our null results reflect a true lack of association or difference between associations. The limited number of esophageal cancer cases also precluded investigation of subtypes of this cancer. Finally, because weight cycling was self-reported, there may be some misclassification due to incorrect responses.
In summary, the results of this study indicate that weight cycling, independent of BMI, is not associated with overall cancer risk or risk of any specific cancer in either men or women. Therefore, overweight and obese individuals should be encouraged to attempt to lose weight even though the weight lost may be regained.
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