Obesity Epidemiology

206 EPIDEMIOLOGIC STUDIES OF CONSEQUENCES OF OBESITYpredicted by measures of central adiposity than by BMI. This is most clear in studiesin women, where BMI is a weak predictor of colorectal cancer (because women aremore likely than men to carry adiposity peripherally rather than centrally). However,recent studies show that waist circumference and WHR are strong predictors of colorectalcancer in women, as they are in men. 36-38 In contrast, for postmenopausal breast cancer,where risk is largely driven by the increased levels of circulating estrogens, centraladiposity is not a better predictor of risk than overall adiposity as estimated by BMI. 21 Itis quite likely that the variability across studies in estimates of risk associated with BMIfor pancreas and liver cancer is partly due to the use of BMI as the measure of exposurerather than a measure of central adiposity.Adult weight gain is a stronger predictor of postmenopausal breast cancer thanBMI. 22-25 BMI reflects both lean body mass and adipose, whereas weight gain throughoutadult life reflects primarily the accumulation of excess adipose tissue. Thus, weight gainis likely a more precise measure of the relevant exposure (e.g., adipose) than BMI. Inaddition, because obesity before the menopause is associated with a lower risk of breastcancer, women who are obese throughout their life have their lifetime risk pulled in twoopposite directions. The women at greatest lifetime risk of breast cancer are those whoare lean in the premenopausal period and become heavier in the postmenopausal period.Adult weight gain measures this, whereas a single BMI does not.Effect ModificationWhile the impact of adiposity on cancer risk generally operates across all subgroupsof individuals, there are documented exceptions. The most obvious is the well-documentedmodification by menopausal status of the effect of adiposity on breast cancerrisk. Another is the apparent difference by gender for colorectal cancer risk as notedalready. However, when the correct measure of central adiposity is used rather thangeneral adiposity, the risks in both men and women are stronger and more similar toone another. 36Another subgroup difference relates to adiposity, exogenous hormone use, and risk ofpostmenopausal breast cancer. Both BMI and weight gain are related to risk of breastcancer only among postmenopausal women who have never used (or in some cases notcurrently using) hormone replacement therapy (HRT). 20,23,27,152-156 This finding has beenreplicated consistently and lends support to the hypothesis that adiposity increases postmenopausalbreast cancer risk through its estrogenic effects. Lean women who are notusing HRT have the lowest levels of circulating estrogens and the lowest risk of breastcancer. In HRT users, both lean and heavy women have high levels of circulating estrogensby virtue of their HRT use and have similar risk of breast cancer; against thisbackground, the estrogenic effect of obesity is imperceptible and does not increase riskfurther.The impact of adiposity may also vary according to characteristics of the cancer,including stage, tumor characteristics, subsite, or histology. Adiposity predicts foradvanced but not local prostate cancer. Adiposity is associated with more aggressivebreast cancers but with less aggressive endometrial cancers. Several studies suggestthat the association between adiposity and breast cancer varies by estrogen and progesteronereceptor status. 26,156 Adiposity predicts more strongly for colon cancer than forrectal cancer, and is a strong risk factor for adenocarcinoma of the esophagus but notfor squamous cell carcinoma of the esophagus. To the extent possible, studies shouldexamine the impact of adiposity by subgroups of individuals and by subtypes of canceroutcome.