1. Perron, Michelle

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A recent long-term study of women identified a likely association between being overweight or obese as a teenager and developing endometrial cancer later in life. The research should spur greater clinical and population health efforts to reduce obesity in children and adolescents.

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"Obesity is an important risk factor for many adverse health outcomes. We have had a longstanding interest in developing a better understanding of that role," said Peggy Reynolds, PhD, Senior Research Scientist at the Cancer Prevention Institute of California in Berkeley. Reynolds was a coauthor of the article that reported the study findings in Cancer Causes & Control (2016;27(12):1419-28).


Study Design

The research team at the Cancer Prevention Institute of California evaluated 88,142 women who had enrolled in the California Teacher Study, a statewide project that has followed more than 130,000 current and former California teachers since 1995.


The researchers asked participants to complete a self-administered questionnaire that encompassed health and medical history and included queries about hormone therapy use and body size. They completed the questionnaire at the time they enrolled in the study and answered three additional surveys between then and 2006. Only women who had not had endometrial cancer prior to joining the study were included in this most recent analysis.


Between 1997 and 2012, 887 women in the study were diagnosed with invasive type 1 endometrial cancer. Researchers found that, among women not taking menopausal hormone therapy, adolescent obesity contributed to endometrial cancer risk no matter what the subjects' body weight in adulthood.



Multivariable Cox proportional hazards models provided estimates of hazard rates (HR) and 95 percent confidence intervals for endometrial cancer associated with life-course body size phenotypes, which incorporated validated measures.


Among women who reported current use of hormone therapy to manage postmenopause symptoms, endometrial cancer risk was only associated with height (HR 1.78, 95% CI 1.32-2.40 for >67 vs. <67 inches). Among women who did not report using hormone therapy, tall women who were overweight or obese in adolescence (HR 4.33, 95% CI 2.51-7.46) or who became overweight or obese as adults (HR 4.74, 95% CI 2.70-8.32) were at greatest risk.


"Considering absolute body mass, changes in adiposity over time, and body fat distribution together, instead of each measure alone, we identified lifetime obesity phenotypes associated with endometrial cancer risk," the authors wrote. "These results more clearly define specific risk groups, and may explain inconsistent findings across studies, improve risk prediction models, and aid in developing targeted interventions for endometrial cancer."


Clinical Implications

Reynolds, a member of the research team, shared further insight in an interview with Oncology Times. "We know that obesity in adulthood is a risk factor for endometrial cancer, and we also know that exposure to unopposed estrogen is a risk factor," Reynolds noted. "This study was designed to assess more carefully what features of overweight or obesity over the life course might be most important in understanding the role of body size, particularly in the absence of the powerful influence of hormone replacement therapy."


Aspects of obesity, such as overall body mass, body fat distribution, and weight gain, have been associated with endometrial cancer risk in women who don't use hormone therapy. This risk has also been noted in women with greater height, Reynolds explained.


"We wanted to understand how these various aspects of body size operate together and over a woman's lifetime to increase risk. This is particularly important given the obesity epidemic of the last several decades and the widespread cessation of hormone therapy following the publication of the Women's Health Initiative clinical trial results in 2002."


When asked about the study's implications for the clinical care of adolescent girls, Reynolds called the findings one more piece of evidence that obesity in youth can contributed to important health consequences later in life. "It suggests that adolescent obesity puts a woman at risk for the development of endometrial cancer decades later and points to the importance of preventing childhood and adolescent obesity," she explained.


The scope of increased cancer risk identified by the research team was significant and merits greater attention in the clinical setting. "Because we also saw that the most pronounced risks for endometrial cancer were for lifelong obesity-with 4-5 times higher risk in these women compared to those who maintained normal weight over the life course-this also contributes to the evidence for weight control even later in life," Reynolds said.


"While lifelong overweight and obesity increase risk most substantially, especially among tall women (5 foot 7 inches and taller), overweight and obesity in adulthood alone also increase risk. Thus, weight control throughout life is important," she continued.


So how widespread is obesity in adults and adolescents? A population analysis published earlier this year found that 40.5 percent of adult U.S. women were obese in 2013-2014 (JAMA 2016;315(21):2284-91). This health problem clearly has its roots in childhood: a separate analysis found that between 2011 and 2014, the prevalence of obesity in U.S. children and adolescents was 17.0 percent.


The Future

Although the Cancer Prevention Institute of California doesn't have specific follow-up plans on the endometrial risk finding, Reynolds said the results will continue to influence clinical research and care.


"The issue of the influence of body size is likely to play an important role in other cancers, especially breast cancer," she concluded. "To that extent, we may do similar types of analyses for other cancers and disease outcomes."


Michelle Perron is a contributing writer.