Weight Cycling and Cancer Incidence
Weight Cycling and Cancer Incidence
A large proportion of CPS-II Nutrition Cohort participants reported some weight cycling. More women (57%) than men (43%) weight cycled, and women were more likely to report higher numbers of weight cycles than men.
Weight cyclers tended to be younger, were more likely to be former smokers and to have a history of diabetes, and were less likely to be current smokers than noncyclers (Table 1 (men) and Table 2 (women)). Weight cyclers also had a higher BMI at age 18, in 1982, and in 1992 and gained more weight in the intervals between age 18 and 1982 and between 1982 and 1992 than did noncyclers. Women weight cyclers were also more likely to be former postmenopausal hormone users and less likely to be current postmenopausal hormone users and to have a higher energy intake and a lower alcohol consumption.
The associations of weight cycling with risk of all cancer and 11 individual cancers for men and women combined are shown in Table 3. The associations for men and women separately for these cancers plus 4 sex-specific cancers are shown in Web Table 2 http://aje.oxfordjournals.org/content/182/5/394/suppl/DC1. In men and women combined and in women only, weight cycling was associated with overall cancer risk before but not after adjustment for BMI at baseline in 1992. In men alone, weight cycling was not associated with overall cancer risk in either model.
The association between weight cycling and prostate cancer risk, which accounted for almost 47% of all cancers in men, was null, regardless of whether BMI was included in the model. No association was observed when only aggressive prostate cancers were examined. The associations with postmenopausal breast and endometrial cancers were similar to those for overall cancer risk in women, where a positive association was observed before but not after adjustment for BMI. There was no association between weight cycling and ovarian cancer risk either prior to or after adjustment for BMI.
Weight cycling was not statistically significantly associated with a number of other cancers, including colon, rectal, pancreatic, renal, esophageal, liver, lung, and stomach cancers, non-Hodgkin lymphoma, multiple myeloma, and melanoma, in both men and women (Table 2 and Web Table 2 http://aje.oxfordjournals.org/content/182/5/394/suppl/DC1).
The associations with cancer risk determined by using weight cycling as a continuous variable before and after adjustment for BMI in men and women separately are shown in Figures 1 and 2. The only statistically significant association after adjustment for BMI was for esophageal cancer in women. However, this analysis included only 35 cases (20 weight cycling cases).
(Enlarge Image)
Figure 1.
Association of weight cycling with cancer incidence in men in the Cancer Prevention Study II Nutrition Cohort. Hazard ratios (HRs) and 95% confidence intervals (CIs) are shown for each cancer for analyses adjusted for age, race, education, smoking status, physical activity, nonsteroidal antiinflammatory drug use, and history of diabetes (A) and all these variables plus body mass index expressed as weight (kg)/height (m) in 1992 (continuous) (B). The HR is the association per 5 weight cycles determined by using weight cycles as a continuous variable. All analyses for prostate cancer are additionally adjusted for prostate-specific antigen screening starting in 1997 (time dependent), and all analyses for colon and rectal cancer are additionally adjusted for colorectal endoscopy starting in 1997 (time dependent).
(Enlarge Image)
Figure 2.
Association of weight cycling with cancer incidence in women in the Cancer Prevention Study II Nutrition Cohort. Hazard ratios (HRs) and 95% confidence intervals (CIs) are shown for each cancer for analyses adjusted for age, race, education, smoking status, physical activity, nonsteroidal antiinflammatory drug use, history of diabetes, and postmenopausal hormone use (A) and all these variables plus body mass index expressed as weight (kg)/height (m) in 1992 (continuous) (B). The HR is the association per 5 weight cycles determined by using weight cycles as a continuous variable. All analyses for breast cancer are additionally adjusted for mammography starting in 1992 (time dependent), and all analyses for colon and rectal cancer are additionally adjusted for colorectal endoscopy starting in 1997 (time dependent).
Because a recent analysis of weight cycling and endometrial cancer found a statistically significant interaction with history of obesity (BMI <30), we examined associations stratified by obesity status. "Never obese" individuals were those whose BMI was <30 at age 18, in 1982, and in 1992, whereas "ever obese" individuals reported having a BMI ≥30 at 1 or more of these time points. The results of these analyses for overall cancer risk, the most common cancers in men and women (prostate and postmenopausal breast), kidney cancer in men, and endometrial cancer in women are shown in Figures 3 (men) and 4 (women). These associations, as well as those for all other cancers (Web Table 3 http://aje.oxfordjournals.org/content/182/5/394/suppl/DC1), were null regardless of history of obesity. Although the point estimates were above 1 for some cancers among the ever obese and primarily less than or equal to 1 for the never obese, the interaction was not statistically significant for any cancer in either sex.
(Enlarge Image)
Figure 3.
Association of weight cycling with overall, prostate, and renal cancer risk in men stratified by obesity status in the Cancer Prevention Study II Nutrition Cohort, 1992. Obesity status: A) never obese, body mass index <30; B) ever obese, body mass index ≥30. Hazard ratios (HRs) and 95% confidence intervals (CIs) were determined in analyses for age, race, education, smoking status, physical activity, nonsteroidal antiinflammatory drug use, history of diabetes, and body mass index expressed as weight (kg)/height (m) in 1992 (continuous).
(Enlarge Image)
Figure 4.
Association of weight cycling with overall, breast, and endometrial cancer risk in women stratified by obesity status in the Cancer Prevention Study II Nutrition Cohort, 1992. Obesity status: A) never obese, body mass index <30; B) ever obese, body mass index ≥30. Hazard ratios (HRs) and 95% confidence intervals (CIs) were determined in analyses for age, race, education, smoking status, physical activity, nonsteroidal antiinflammatory drug use, history of diabetes, postmenopausal hormone use, and body mass index expressed as weight (kg)/height (m) in 1992 (continuous).
Whether the association of weight cycling with cancer risk varied by age was investigated in stratified analyses with either younger or older participants defined relative to the median age of the study population (64 years for men and 62 years for women). In older women aged ≥62 years, there was a statistically significant positive trend between number of cycles and ovarian cancer (for 1–4 cycles: hazard ratio (HR) = 1.02, 95% confidence interval (CI): 0.72, 1.44; for 5–9 cycles: HR = 1.89, 95% CI: 1.15, 3.13; for ≥10 cycles: HR = 2.07, 95% CI: 1.23, 3.50) (P for trend = 0.03), whereas the association was null in younger women aged <62 years (for 1–4 cycles: HR = 0.88, 95% CI: 0.60, 1.29; for 5–9 cycles: HR = 1.13, 95% CI: 0.66, 1.95; for ≥10 cycles: HR = 0.68, 95% CI: 0.36, 1.28) (P for trend = 0.41). However, the age-specific associations of weight cycling with ovarian cancer risk were not statistically significantly different (P for interaction = 0.12). All other associations with weight cycling in younger and older men and women were null (data not shown).
Although smoking status was controlled for in analyses of weight cycling and cancer risk, it is possible that residual confounding by smoking dose could influence our findings. Therefore, in sensitivity analyses, the study population was limited to never and long-term former (≥20 years) smokers. All associations were null and similar to those obtained with the full study population (data not shown).
Results
A large proportion of CPS-II Nutrition Cohort participants reported some weight cycling. More women (57%) than men (43%) weight cycled, and women were more likely to report higher numbers of weight cycles than men.
Weight cyclers tended to be younger, were more likely to be former smokers and to have a history of diabetes, and were less likely to be current smokers than noncyclers (Table 1 (men) and Table 2 (women)). Weight cyclers also had a higher BMI at age 18, in 1982, and in 1992 and gained more weight in the intervals between age 18 and 1982 and between 1982 and 1992 than did noncyclers. Women weight cyclers were also more likely to be former postmenopausal hormone users and less likely to be current postmenopausal hormone users and to have a higher energy intake and a lower alcohol consumption.
The associations of weight cycling with risk of all cancer and 11 individual cancers for men and women combined are shown in Table 3. The associations for men and women separately for these cancers plus 4 sex-specific cancers are shown in Web Table 2 http://aje.oxfordjournals.org/content/182/5/394/suppl/DC1. In men and women combined and in women only, weight cycling was associated with overall cancer risk before but not after adjustment for BMI at baseline in 1992. In men alone, weight cycling was not associated with overall cancer risk in either model.
The association between weight cycling and prostate cancer risk, which accounted for almost 47% of all cancers in men, was null, regardless of whether BMI was included in the model. No association was observed when only aggressive prostate cancers were examined. The associations with postmenopausal breast and endometrial cancers were similar to those for overall cancer risk in women, where a positive association was observed before but not after adjustment for BMI. There was no association between weight cycling and ovarian cancer risk either prior to or after adjustment for BMI.
Weight cycling was not statistically significantly associated with a number of other cancers, including colon, rectal, pancreatic, renal, esophageal, liver, lung, and stomach cancers, non-Hodgkin lymphoma, multiple myeloma, and melanoma, in both men and women (Table 2 and Web Table 2 http://aje.oxfordjournals.org/content/182/5/394/suppl/DC1).
The associations with cancer risk determined by using weight cycling as a continuous variable before and after adjustment for BMI in men and women separately are shown in Figures 1 and 2. The only statistically significant association after adjustment for BMI was for esophageal cancer in women. However, this analysis included only 35 cases (20 weight cycling cases).
(Enlarge Image)
Figure 1.
Association of weight cycling with cancer incidence in men in the Cancer Prevention Study II Nutrition Cohort. Hazard ratios (HRs) and 95% confidence intervals (CIs) are shown for each cancer for analyses adjusted for age, race, education, smoking status, physical activity, nonsteroidal antiinflammatory drug use, and history of diabetes (A) and all these variables plus body mass index expressed as weight (kg)/height (m) in 1992 (continuous) (B). The HR is the association per 5 weight cycles determined by using weight cycles as a continuous variable. All analyses for prostate cancer are additionally adjusted for prostate-specific antigen screening starting in 1997 (time dependent), and all analyses for colon and rectal cancer are additionally adjusted for colorectal endoscopy starting in 1997 (time dependent).
(Enlarge Image)
Figure 2.
Association of weight cycling with cancer incidence in women in the Cancer Prevention Study II Nutrition Cohort. Hazard ratios (HRs) and 95% confidence intervals (CIs) are shown for each cancer for analyses adjusted for age, race, education, smoking status, physical activity, nonsteroidal antiinflammatory drug use, history of diabetes, and postmenopausal hormone use (A) and all these variables plus body mass index expressed as weight (kg)/height (m) in 1992 (continuous) (B). The HR is the association per 5 weight cycles determined by using weight cycles as a continuous variable. All analyses for breast cancer are additionally adjusted for mammography starting in 1992 (time dependent), and all analyses for colon and rectal cancer are additionally adjusted for colorectal endoscopy starting in 1997 (time dependent).
Because a recent analysis of weight cycling and endometrial cancer found a statistically significant interaction with history of obesity (BMI <30), we examined associations stratified by obesity status. "Never obese" individuals were those whose BMI was <30 at age 18, in 1982, and in 1992, whereas "ever obese" individuals reported having a BMI ≥30 at 1 or more of these time points. The results of these analyses for overall cancer risk, the most common cancers in men and women (prostate and postmenopausal breast), kidney cancer in men, and endometrial cancer in women are shown in Figures 3 (men) and 4 (women). These associations, as well as those for all other cancers (Web Table 3 http://aje.oxfordjournals.org/content/182/5/394/suppl/DC1), were null regardless of history of obesity. Although the point estimates were above 1 for some cancers among the ever obese and primarily less than or equal to 1 for the never obese, the interaction was not statistically significant for any cancer in either sex.
(Enlarge Image)
Figure 3.
Association of weight cycling with overall, prostate, and renal cancer risk in men stratified by obesity status in the Cancer Prevention Study II Nutrition Cohort, 1992. Obesity status: A) never obese, body mass index <30; B) ever obese, body mass index ≥30. Hazard ratios (HRs) and 95% confidence intervals (CIs) were determined in analyses for age, race, education, smoking status, physical activity, nonsteroidal antiinflammatory drug use, history of diabetes, and body mass index expressed as weight (kg)/height (m) in 1992 (continuous).
(Enlarge Image)
Figure 4.
Association of weight cycling with overall, breast, and endometrial cancer risk in women stratified by obesity status in the Cancer Prevention Study II Nutrition Cohort, 1992. Obesity status: A) never obese, body mass index <30; B) ever obese, body mass index ≥30. Hazard ratios (HRs) and 95% confidence intervals (CIs) were determined in analyses for age, race, education, smoking status, physical activity, nonsteroidal antiinflammatory drug use, history of diabetes, postmenopausal hormone use, and body mass index expressed as weight (kg)/height (m) in 1992 (continuous).
Whether the association of weight cycling with cancer risk varied by age was investigated in stratified analyses with either younger or older participants defined relative to the median age of the study population (64 years for men and 62 years for women). In older women aged ≥62 years, there was a statistically significant positive trend between number of cycles and ovarian cancer (for 1–4 cycles: hazard ratio (HR) = 1.02, 95% confidence interval (CI): 0.72, 1.44; for 5–9 cycles: HR = 1.89, 95% CI: 1.15, 3.13; for ≥10 cycles: HR = 2.07, 95% CI: 1.23, 3.50) (P for trend = 0.03), whereas the association was null in younger women aged <62 years (for 1–4 cycles: HR = 0.88, 95% CI: 0.60, 1.29; for 5–9 cycles: HR = 1.13, 95% CI: 0.66, 1.95; for ≥10 cycles: HR = 0.68, 95% CI: 0.36, 1.28) (P for trend = 0.41). However, the age-specific associations of weight cycling with ovarian cancer risk were not statistically significantly different (P for interaction = 0.12). All other associations with weight cycling in younger and older men and women were null (data not shown).
Although smoking status was controlled for in analyses of weight cycling and cancer risk, it is possible that residual confounding by smoking dose could influence our findings. Therefore, in sensitivity analyses, the study population was limited to never and long-term former (≥20 years) smokers. All associations were null and similar to those obtained with the full study population (data not shown).
