In total, 1
630 women who had not been registered with a cancer (other than non-melanoma skin cancer) at the time of recruitment and for whom BMI could be calculated were eligible for analysis. Among these women, the average age at recruitment was 55.9 years. During an average follow-up period of 5.4 years for cancer incidence and 7.0 years for cancer mortality, 45
037 incident cancers and 17
203 deaths from cancer occurred. For some cancers typically associated with a very short survival time—namely, lung, pancreas, and brain cancer—the number of deaths was larger than the number of incident cases because of the slightly longer period of follow-up for mortality than for incidence. When we compared sociodemographic and lifestyle characteristics of women in three broad categories of BMI, we found that BMI was strongly associated with almost all of the characteristics examined (table 1). In particular, women with higher BMI tended to come from a lower socioeconomic class; were less likely to smoke, drink, and use hormone replacement therapy; and had more children than women with lower BMI.
Table 1 Characteristics of the study population at recruitment, and details of follow-up, according to body mass index. Values are percentages (numbers) unless stated otherwise
Table 2 shows the relative risk of cancer incidence for all cancers and for each of the 17 specific sites or types considered, according to BMI, adjusted for age, geographical region, socioeconomic status, age at first birth, parity, smoking status, alcohol intake, physical activity, and, where appropriate, years since menopause and use of hormone replacement therapy. Table 3 shows corresponding relative risks for cancer mortality. The relations between BMI and cancer incidence and mortality for all cancers combined, and for 11 selected sites, are presented graphically in figure 1.
Table 2 Relative risk* of cancer incidence for individual cancer sites or types according to body mass index
Table 3 Relative risk* of cancer mortality for individual cancer sites or types according to body mass index
Fig 1Relative risk of cancer incidence and mortality for individual cancer sites or types according to body mass index (22.5-24.9=reference group). Adjusted for age, geographical region, socioeconomic status, age at first birth, parity, smoking (more ...)
We found significant heterogeneity in the relative risk of cancer incidence across BMI categories for all cancers (P<0.0001), adenocarcinoma of the oesophagus (P=0.0009), squamous cell carcinoma of the oesophagus (P<0.0001), pancreatic cancer (P=0.03), lung cancer (P<0.0001), postmenopausal breast cancer (P<0.0001), endometrial cancer (P<0.0001), kidney cancer (P=0.0005), and leukaemia (P=0.0007). Although a general test for heterogeneity across the five categories of BMI was not statistically significant for ovarian cancer (P=0.1), non-Hodgkin's lymphoma (P=0.2), or multiple myeloma (P=0.1), a more directed test of linear trend in the log relative risks with increasing BMI was significant for each of these cancers (P=0.02 for each type of cancer).
For most of the sites that showed significant heterogeneity in risk according to BMI, the relative risk of cancer increased with increasing BMI. The exceptions to this pattern were squamous cell carcinoma of the oesophagus and lung cancer, for which we found trends of decreasing risk with increasing BMI (P<0.0001 in both cases). As lack of physical activity may be causally related to high BMI, we repeated the analyses in tables 2 and 3 without adjustment for physical activity, but the results were essentially unchanged. We also repeated analyses with inclusion of an interaction term for smoking and alcohol status in the model, but this made little difference to the results. Nor did the results change materially when we restricted analyses to women with complete information for all of the adjustment factors.
In general, the patterns for cancer mortality according to BMI were broadly similar to those for cancer incidence, and most cancer sites that showed a significant trend in the relative risk of incidence with increasing BMI also showed a similar trend in the risk of mortality with increasing BMI. For stomach cancer, colorectal cancer, malignant melanoma, cervix cancer, bladder cancer, and brain cancer, we found no significant evidence of any variation in the overall risk of incidence or mortality according to BMI. Analyses of colorectal cancer risk according to subsite yielded similar results for colon cancer (relative risks in BMI categories <22.5, 22.5-24.9 (reference), 25.0-27.4, 27.5-29.9, and ≥30 were 1.01, 1.00, 1.03, 0.99, and 1.01) and rectal cancer (1.04, 1.00, 1.05, 1.06, and 1.00).
Figure 2 presents, in order of decreasing magnitude, the estimated relative risk of cancer incidence associated with an increase of 10 units in BMI for each individual cancer site or type for all women and within certain subgroups. Based on all women, sites for which we found a significant positive trend in the relative risk of incidence with BMI were endometrial cancer (relative risk per 10 unit increase in BMI=2.89, 95% confidence interval 2.62 to 3.18), adenocarcinoma of the oesophagus (2.38, 1.59 to 3.56), kidney cancer (1.53, 1.27 to 1.84), leukaemia (1.50, 1.23 to 1.83), postmenopausal breast cancer (1.40, 1.31 to 1.49), multiple myeloma (1.31, 1.04 to 1.65), pancreatic cancer (1.24, 1.03 to 1.48), non-Hodgkin's lymphoma (1.17, 1.03 to 1.34), and ovarian cancer (1.14, 1.03 to 1.27). The only cancers for which we found a significant inverse association between BMI and cancer incidence were squamous cell carcinoma of the oesophagus (0.26, 0.18 to 0.38) and lung cancer (0.74, 0.67 to 0.82). We also found evidence of a decrease in the risk of premenopausal breast cancer with increasing BMI (0.86, 0.73 to 1.00), although this was of borderline statistical significance (P=0.05). The trend in the risk of all cancers combined associated with a 10 unit increase in BMI was 1.12 (1.09 to 1.14). When we recalculated trend estimates incorporating updated information on BMI from the first re-survey, the results were essentially unchanged.
Fig 2Estimated trend in the relative risk of cancer incidence by site or type per 10 unit increase in body mass index (BMI). Adjusted for age, geographical region, socioeconomic status, age at first birth, parity, smoking status, alcohol intake, (more ...)
Most sites that showed a significant association with BMI among all women also showed a similar magnitude of association in never smokers, although the trend estimate in never smokers did not always achieve statistical significance. For lung cancer, the trend among never smokers was non-significant (0.82, 0.59 to 1.13) and somewhat attenuated compared with that in all women (0.74, 0.67 to 0.82). For other smoking related cancers (namely, kidney cancer and adenocarcinoma of the oesophagus) and for leukaemia, the trend in risk with increasing body mass index became greater in magnitude after restriction to never smokers. The trend in risk per 10 unit increase in BMI for all cancers combined was also slightly greater in never smokers (1.20, 1.15 to 1.24) than in all women (1.12, 1.09 to 1.14). When we repeated analyses excluding the first two years of follow-up, the trend estimates were not materially altered.
Figure 3 presents the trend estimates in premenopausal women and postmenopausal never users of hormone replacement therapy for cancer sites with more than 50 cases in women who reported being premenopausal at recruitment. We found significant differences in the trend estimates between premenopausal women and postmenopausal never users of hormone replacement therapy for breast cancer (P<0.0001), endometrial cancer (P=0.0001), colorectal cancer (P=0.03), and malignant melanoma (P=0.05). For colorectal cancer and malignant melanoma, we found positive trends in risk with BMI in premenopausal women (relative risk per 10 unit increase 1.61 and 1.62), but we found no evidence of any association in postmenopausal never users of hormone replacement therapy (0.99 and 0.92). By contrast, increased BMI was associated with a decreased risk of breast cancer in premenopausal women (relative risk 0.86) and an increased risk in postmenopausal women (1.40). For endometrial cancer, we found a significant increase in risk with increasing BMI for both groups, but the magnitude of the trend was substantially greater in postmenopausal women than in premenopausal women (relative risk 3.98 compared with 1.77). Thus, in total, we found a significant increase in risk with increasing BMI in 10 out of the 17 specific types of cancer considered, including eight sites in which a positive association existed in all women and two sites in which it was confined to either premenopausal women (colorectal cancer) or postmenopausal women (breast cancer).
Fig 3Estimated relative risk of incidence per 10 unit increase in body mass index (BMI) for cancer sites with at least 50 cases in premenopausal women, by menopausal status at entry in never users of hormone replacement therapy. Adjusted for (more ...)
Table 4 presents (for postmenopausal women only) the proportions of incident cancers attributable to being overweight or obese, and to being obese, for those cancers that showed a significant increase in risk with increasing BMI. The estimated proportion of all cancers attributable to being overweight or obese among postmenopausal women was 5%. For endometrial cancer and adenocarcinoma of the oesophagus, about a half of cases (51% and 48%) were attributable to being overweight or obese. By comparison, the estimated proportion of cancers attributable to being overweight or obese was between 10% and 20% for multiple myeloma, kidney cancer, leukaemia, and pancreatic cancer and below 10% for all other specific sites or types listed in table 4. Estimates of attributable risk obtained by using unstratified relative risk estimates did not differ materially from those in the table.
Table 4 Estimated proportion of all cancers, and of cancers of specific sites, attributable to overweight and obesity in postmenopausal women in UK