The exact mechanism(s) behind the association between obesity and some cancers is unknown. Obesity itself develops via complex mechanisms involving interactions between heredity and lifestyle changes that include nutritional and exercise considerations. Even the location of the fat deposits may provide clues as to the pathogenesis, as described below.38 The general thought is that augmented fat deposits lead to hormonal imbalances. For example, high levels of estrogens contribute to the proclivity toward cancer. The increased risk of breast cancer after menopause in obese women is believed to be due to increased levels of estrogens.39 Prior to menopause, the ovaries are the primary source of estrogen. After menopause, when ovaries stop producing estrogen, fat tissue becomes the primary source.39 Logic dictates that more fat leads to more circulating estrogens and, hence, an increase in risk.
In an international study from three weight centers, blood samples were collected from almost 3000 women who were not using hormone-replacement therapy.39 A total of 624 women developed breast cancer in the 2- to 12-year follow-up. Hormones in the afflicted were compared with the normals, and the subjects were categorized according to their BMI. In short, as BMI climbed, so did estrogen levels and breast cancer risk. Women with a BMI of 30 had an 18% higher risk of developing breast cancer than women with a BMI of 25.
Obesity not infrequently portends the development of insulin resistance, with high circulating levels of insulin and insulinlike hormones—very important growth factors.40 Insulin is known to stimulate cell proliferation, suggesting that an overproduction or high concentrations may be responsible, at least to some extent, for cancer development. High insulin and insulinlike hormone levels have been associated with increased risk for breast cancer and poorer survival after breast cancer diagnosis.31 An increased waist-to-hip ratio is a recognized marker of insulin resistance and hyperinsulinemia. The fact that an elevated ratio proved to be a predictor of breast cancer mortality supports the importance of some role for a perturbed insulin system in the pathogenesis of cancer, at least breast cancer.31 Among premenopausal women, central obesity may be specifically associated with an increased risk of breast cancer.41
Noting that insulin and insulinlike growth factors such as IGFI and II and IGF-binding proteins such as IGFBP 1 and 3 have been implicated in breast cancer outcomes, 53 postmenopausal breast cancer survivors were randomly assigned to an exercise (n=25) or control group (n=28) for 15 weeks.42 No significant intergroup differences were noted in fasting insulin, glucose, IGF II, or IGFBP 1. However, the changes in IGF I, IGFBP 3, and IGF 1/IGFBP 3 molar ratio between the exercise and control groups were significant. Accordingly, the possibility that exercise could be helpful in the treatment of breast cancer via its effects on the insulin system is strengthened.
An additional point to consider is that different forms of cancer may respond differently to obesity.
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