Obesity's Impact on Uterine Cancer Risk Greater in Younger Age Groups

TAMPA, Fla. -- Obesity poses a significantly greater risk of uterine cancer in younger women as compared with their older counterparts, an analysis of a database from Taiwan showed.

The relative risk of uterine cancer in women with obesity versus normal-weight women increased from 2.6 in the 65+ age group to as much as 39 times greater in women 20 to 24. The risk of endometrioid uterine cancer, the histology most closely associated with obesity, increased from 3.0 in the 65+ age group to 19 and 32 in the 25-34 and 20-24 age groups, respectively.

Among women who met body mass index (BMI) criteria for overweight, the risk of uterine cancer ranged from 1.3 to 7.7 times greater across age groups as compared with normal-weight women, reported Chelsea Stewart, MD, of the University of California Los Angeles, at the Society of Gynecologic Oncology annual meeting.

"This is the first study to investigate the risk of endometrial cancer based on BMI and age," said Stewart. "Previous studies lacked information on age and cell type and/or did not evaluate risk of endometrial cancer at a specific age."

"Overall, compared to normal-weight patients, those who are obese or overweight have a higher risk of uterine cancer," she added. "Specifically, obesity in younger patients poses a significantly higher risk compared to older patients, up to almost 40-fold higher. Future research should evaluate risk of uterine cancer adjusted for duration of obesity, fat distribution, and lean versus fat mass."

During a discussion that followed the talk, Megan Clarke, PhD, a research scientist at the National Cancer Institute, asked Stewart for more specifics about the data: the number of cases of uterine cancer in the youngest age group (20-24) with obesity and the confidence intervals associated with the statistically significant risk conferred by obesity in that age group.

Stewart said 11 cases of uterine cancer occurred in women with obesity versus three normal-weight women in the 20-24 age group, and the confidence intervals associated with the risk in that age group ranged from 11 to 139. The researchers performed additional analyses for patients and controls younger than 30 and obtained results associated with a P value <0.001, she added.

In response to another question from Clarke, Stewart said the researchers did not have information about women who had hysterectomies and did not know whether those women had been excluded.

Multiple studies have documented increasing rates of obesity and a corresponding increase in rates of uterine cancer. However, studies to date have lacked data directly linking BMI to cancer. U.S. databases do not have the necessary information, leading Stewart and colleagues to analyze records from Taiwan's Health and Welfare Data Science Center linked to the Statistical Yearbook of Health Promotion. Investigators normalized BMI categories according to Taiwanese standards: normal weight, 18.5-23.0; overweight, 24-27; and obese, ≥27.

From 2008 to 2018, uterine cancer incidence increased from 10 cases per 100,000 to 15.4 per 100,000, representing a 5.9% annual increase. During the same time period, the proportion of overweight and obese individuals increased from 28.4% to 32.4%.

The risk of uterine cancer in overweight versus normal-weight women was 1.3-fold higher in women older than 65 (P<0.001), increasing with age to 7.7-fold higher for women 20-24 (P=0.003). For the comparison of obese versus normal-weight women, the risk of uterine cancer in the 65-or-older age group was 2.6-fold greater, increasing with declining age:

• 55-64: 3.8
• 45-54: 4.2
• 35-44: 10.0
• 25-34: 16.2
• 20-24: 38.9

From 2014 to 2018, the risk of endometrioid uterine cancer for obese versus normal-weight women increased from 3.0 per 100,000 in women 65 or older to 31.8 per 100,000 among women 20-24. The risk of serous, carcinosarcoma, and malignant mesenchymal uterine cancer also increased across the age groups.

Stewart acknowledged several limitations to the study: no information on duration of obesity, the lower number of patients in younger cohorts, lack of diversity in the population studied, and the lack of information on genetic risk and use of unopposed estrogen.

The study did not address potential explanations for the association between obesity and uterine cancer. One recent investigation applied Mendelian randomization to more than a dozen possible molecular risk factors for uterine cancer. The study uncovered "strong evidence" that fasting insulin, bioavailable testosterone, and sex hormone-binding globulin (SHBG) mediate the effect of BMI on uterine cancer risk. The study did not address the variable effect of BMI on cancer risk by age group.

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