Obesity Epidemiology

204 EPIDEMIOLOGIC STUDIES OF CONSEQUENCES OF OBESITYscreening is not a confounder of the relationship between adiposity and poor prognosis,92,94,103,105 nor is mammography any less sensitive among heavier women. 106 Thus,the impact of obesity on prognosis is unlikely to be solely, or even largely, an artifact ofdelayed diagnosis.Another important area of research is the impact of treatment-related weight gain onprognosis for women with breast cancer. Weight gain after diagnosis is common in breastcancer patients who receive adjuvant chemotherapy as part of their treatment. Resultsfrom available studies suggest that weight gain after diagnosis exerts an adverse impacton prognosis, and research in this area is active. 107-109There is accumulating evidence that obesity is associated with an increase in risk ofadvanced prostate cancer or death from prostate cancer. 2,8,81,110-114 Recent studies consistentlyindicate that obese men with prostate cancer are more likely to have aggressivedisease that recurs after radical prostatectomy than nonobese men. 115-118 While still speculative,the mechanisms by which obesity predicts for advanced prostate cancer likelyinvolve the insulin pathway. Several studies suggest that insulin acts to promote prostatecancer development and growth. 119-122 High concentrations of IGF-I 30 and overexpression oftype 1 IGF-I receptor 123,124 are associated with prostate cancer. Studies of circulating leptinlevels and prostate cancer risk are not consistent; while three studies have linked increasedleptin levels to more advanced, higher-grade tumors, 125-127 three other studies have notfound an association. 78,128,129 Decreased adiponectin levels, which indicate decreased insulinsensitivity, have also been linked to high-grade, advanced prostate cancer. 130As with breast cancer, nonbiological issues of screening, detection, and treatment areimportant to the evaluation of the impact of adiposity on prostate cancer prognosis. It canbe harder to perform a digital rectal examination in obese men because of their generaladiposity in combination with larger prostate size. 131,132 In addition, despite larger prostatesizes, obese men may have lower serum levels of prostate- specific antigen (PSA), 133-136potentially biasing them toward later stage at diagnosis even with regular PSA screening.Surgery is more difficult to perform in obese men with a greater risk of positive surgicalmargins. Still, mortality from prostate cancer was found to be increased in obese menin a prospective cohort study conducted from 1950 to 1972, 137 long before PSA screening,and at a time when surgery was rarely done. These results suggest that the adverseimpact of adiposity on prognosis is rooted in biological characteristics of the tumor.Studies on BMI and prognosis among women with endometrial cancer suggestthat heavier women have a better prognostic profile, as indicated by more favorablepathological features, and longer survival. 138-142 This finding lends additional support tothe mechanistic hypothesis of unopposed estrogens, as it mirrors the better prognosticprofile seen in women whose endometrial cancer was induced by estrogen replacementtherapy.There are several studies examining the impact of adiposity on prognosis among colorectalcancer patients. Available studies suggest that adiposity may have an adverseeffect on prognosis, 143-147 although results are somewhat inconsistent by gender and forcolon versus rectal cancer. While obesity is not consistently associated with increasedrisk of ovarian cancer, studies among ovarian cancer patients suggest that obesity mayadversely impact survival. 148-150For breast, prostate, and other cancer patients, obesity may bring added complicationsof multiple comorbidities, resulting in poorer overall survival. In addition, obesity maycompromise efficacy of cancer treatment, both surgery and chemotherapy. Additionalwork is needed to understand the impact of adiposity on prognosis across a wider rangeof cancer sites.