Significant Weight Gain in Adulthood Increased Risk for Endometrial Cancer

Postmenopausal women who gained weight during adulthood had an increased risk for endometrial cancer compared with women who maintained a stable weight, according to data from the American Cancer Society’s Cancer Prevention Study II Nutrition Cohort.

Victoria L. Stevens, Ph.D., strategic director of laboratory services at the National Home Office of the American Cancer Society in Atlanta, presented the data at the 10th AACR International Conference on Frontiers in Cancer Prevention Research, held Oct. 22-25, 2011.

Stevens and colleagues investigated whether adulthood weight gain and/or weight cycling, defined as the number of times a woman purposefully lost 10 pounds or more and then later regained the weight, increased the risk for endometrial cancer in postmenopausal women, independent of body mass index (BMI). Weight cycling, commonly referred to as “yo-yo” dieting, had previously been suggested to increase the amount of fat mass relative to lean body mass, according to Stevens.

“Fat tissue is the major source of circulating estrogen in postmenopausal women, and estrogen promotes the development of endometrial cancer,” Stevens said. “Therefore, we hypothesized that weight cycling could be associated with risk for this cancer because women who engage in this behavior may have a higher proportion of fat than noncyclers.”

The researchers collected data from 38,152 women with an intact uterus and who provided information on weight history and weight cycling on a 1992 questionnaire. Between 1992 and 2007, 560 women reported a diagnosis of endometrial cancer.

Overall, the results indicated that there was an almost fourfold increased risk for endometrial cancer in women who had gained 61 pounds or more in that timeframe, compared with women who maintained a stable weight. After adjustment for baseline BMI, the researchers found a twofold increased risk for endometrial cancer.

Endometrial Cancer Risk Factors
Before menopause, the ovaries normally produce two main types of hormones: estrogen and progesterone. Estrogen promotes endometrial cell growth; progesterone inhibits it. Endometrial cancer is more common in women who have consistently high circulating levels of estrogen and low levels of progesterone. Any factor that leads to increased relative exposure to estrogen over time also leads to an increased risk of endometrial cancer.

The key risk factors for endometrial cancer are:

  * obesity - particularly being more than 50 pounds overweight (fat tissue can convert other hormones in the body into estrogens)
  * early menstruation (periods starting before age 12)
  * late menopause (after age 52)
  * never having given birth or a history of infertility (an inability to become pregnant)
  * ovarian diseases, such as polycystic ovaries, that may cause a woman to have higher-than-normal estrogen levels and lower-than-normal progesterone levels
  * tamoxifen use

In addition, after adjustment, the researchers found no association between weight cycling, or yo-yo dieting, and endometrial cancer risk. “Weight gain during adulthood may increase risk for endometrial cancer in postmenopausal women, but weight cycling, which results from unsuccessful attempts to lose weight, does not increase risk for this cancer,” Stevens said.

Future research should address whether the timing of weight gain and weight cycling during specific parts of adulthood, such as early adulthood versus middle age, influences the risk for endometrial cancer and whether weight loss decreases this risk, Stevens said.

“Weight gain during adulthood should be avoided to minimize risk for endometrial cancer,” she said. “Women who have gained weight and are overweight or obese should continue to attempt to lose weight even though most weight loss will not be maintained.”

Although most cases of endometrial cancer occur in postmenopausal women, younger women who have been exposed to unopposed estrogen are at risk too. The first half of a normal menstrual cycle is characterized by proliferative changes, with estrogen as the main force. Following ovulation, mainly in response to progesterone, secretory changes are induced without further proliferation. If a patient is anovulatory, proliferation will continue without progesterone “control” and may lead to hyperplasia and even cancer. The various types of hyperplasia are simple hyperplasia, complex with atypia, and complex without atypia. Complex hyperplasia with atypia has a 25% risk of progressing to cancer if left untreated. Obesity increases estrogen exposure, partly because it is frequently accompanied by anovulation. Additionally, aromatase in fat tissue leads to the conversion of androgen to estrogen. Lower sex hormone-binding globulin levels are also associated with an increased amount of free sex steroids.

Thomas CC, Wingo PA, Dolan MS, Lee NC, Richardson LC
Obstet Gynecol. 2009;114:22-27

Peter Kovacs, MD, PhD

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Source: American Association for Cancer Research (AACR)

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