Cumulative abdominal obesity exposure and risk of endometrial cancer in young women: a population-based cohort study

doi:10.21203/rs.3.rs-4881494/v1

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Cumulative abdominal obesity exposure and risk of endometrial cancer in young women: a population-based cohort study

https://doi.org/10.21203/rs.3.rs-4881494/v1

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BACKGROUND

Abdominal obesity is currently being investigated as an indicator of adiposity and cancer risk, and its prevalence is increasing in young women. This study aimed to examine whether cumulative abdominal obesity exposure in young women was associated with the development of endometrial cancer.

METHODS

We used data from the South Korean National Health Insurance Service for women aged 20–39 years who had completed four consecutive annual health examinations between 2009 and 2015 and had no history of cancer at baseline. Participants were categorized into five groups based on the number of abdominal obesity exposures (waist circumference ≥ 85 cm). Exposure numbers ranged from 0 to 4, indicating the frequency of abdominal obesity across the four health examinations over 4 years. The primary outcome was newly diagnosed endometrial cancer during a follow-up period of 7.12 years.

RESULTS

Among the 445,791 young women (mean [SD] age 30.82 [4.55] years), 302 (mean [SD], 32.79 [4.53] years) developed endometrial cancer. The cumulative incidence of endometrial cancer differed significantly according to the number of abdominal obesity exposures (log-rank test, P < .001). The incidence of endometrial cancer has progressively increased with abdominal obesity exposure. The multivariable-adjusted HRs for incident endometrial cancer were 1.480 (95% CI, 0.970–2.258), 2.361 (95% CI, 1.391–4.008), 4.114 (95% CI, 2.546–6.647), and 6.215 (95% CI, 4.250–9.088) for participants with exposure numbers of 1–4, respectively, compared with those with an exposure number of 0.

CONCLUSION

In this population-based nationwide cohort study of young women, we observed a progressive increase in the risk of endometrial cancer with cumulative abdominal obesity exposure.

Health sciences/Risk factors

Health sciences/Diseases/Cancer

Health sciences/Endocrinology/Endocrine system and metabolic diseases/Obesity

Abdominal obesity is currently being investigated as an indicator of adiposity and cancer risk, and its prevalence is increasing in young women. In this population-based longitudinal cohort study, we observed a progressive increase in the risk of endometrial cancer with cumulative abdominal obesity exposure in young women aged 20–39 years. In addition, abdominal obesity showed a stronger association with the risk of endometrial cancer than did general obesity, as cumulative exposure increased. These findings underscore the importance of identifying abdominal obesity as a potential risk factor for endometrial cancer in young women.

Abdominal obesity, which is characterized by the accumulation of visceral fat, is currently being investigated as an indicator of adiposity and cancer risk [1]. Although the precise mechanism is not fully understood, obesity-related abnormalities such as impaired glucose tolerance, insulin resistance, and systemic inflammation are expected to contribute to cancer development [2]. Apart from body mass index (BMI), other anthropometric measurements, such as waist-to-hip ratio or waist circumference (WC), are associated with an increased risk of endometrial cancer [3]. However, previous studies have indicated that most endometrial cancers in patients younger than 40 years are associated with general obesity [4]. The role of abdominal obesity in the risk of endometrial cancer, particularly in young women, requires comprehensive exploration.

Endometrial cancer, a gynecological malignancy arising from the inner lining of the uterus, is the most common gynecologic malignancy in developed countries, and its incidence has steadily increased in recent decades [5,6]. The majority of cases occur predominately in women who are postmenopausal; 2‒14% of cases develop in women aged 40 years and younger [7]. The incidence of endometrial cancer continues to increase sharply in younger generations [8]. This demographic shift highlights the need to identify the risk factors that contribute to endometrial cancer development among young women. The faster rise in endometrial cancer occurring before the age of 40 years mirrors similar observations in other cancers, pointing to a possible link with the rising obesity epidemic in younger generations [9].

This population-based nationwide cohort study of young Korean women aimed to assess the risk of endometrial cancer associated with cumulative exposure to abdominal obesity. This study provides valuable insights into the role of abdominal obesity in the development of endometrial cancer in young women, with implications for preventive strategies and public health interventions aimed at reducing the burden of this disease in this vulnerable population.

Data sources

In this large-scale epidemiological study of a Korean cohort, we used the Korean National Health Information Database (NHID), which combines information obtained from the National Health Insurance Service (NHIS) and general health examinations provided to all Korean adults [10]. The NHIS is the only insurer managing the health insurance system in Korea and enrolls approximately 97% of the Korean population. The general health screening program involves annual or biennial health examinations for the entire population of Korean adults aged ≥ 40 years and for regional household members and dependents of people aged ≥ 20 years. The NHID includes claims data, health screening information, detailed lifestyle questionnaires, laboratory results, and anthropometric measurements.

Study population

From the NHID, we identified 471,376 women aged 20–39 years at baseline who underwent at least one health examination between 2009 and 2012 and had three additional consecutive annual health examinations. The index date was defined as the date of the fourth (latest) health examination. Among them, we excluded 20,804 participants with missing data and 3,549 who had been diagnosed with cancer before the index date. We set a 1-year lag period and excluded 1,232 patients diagnosed with uterine corpus cancer to minimize the risk of reverse causality. Consequently, the final study population consisted of 445,791 women, divided into four groups according to their cumulative exposure to abdominal obesity (Fig. 1). This study was approved by the Institutional Review Board of the Hanyang University of Korea (No. HYU-2023-010). Informed consent was waived because anonymous and de-identified information was used for the analysis. This study was conducted in compliance with the principles of the Declaration of Helsinki.

Cumulative abdominal obesity exposure

The WC, weight, and height of the participants were measured in a standardized manner by trained nurses during each examination. We defined abdominal obesity as a WC ≥ 85 cm for Korean women according to the WC cut-off point in the Asian-specific population [11]. WC was measured by trained examiners at the midpoint between the inferior border of the lower rib and the iliac crest on the mid-axillary line after exhalation. General obesity was defined as a BMI ≥ 25 kg/m² according to the Asia-Pacific criteria of the World Health Organization Guidelines [12]. BMI was calculated as weight (kg) divided by height (m) squared.

To estimate cumulative exposure to abdominal obesity, we assessed the frequency of abdominal obesity (WC ≥ 85 cm) across four consecutive annual health examinations over 4 years and counted it as abdominal obesity exposure. In this classification, 0 indicated no abdominal obesity and 1–4 indicated the frequency of abdominal obesity. Additionally, the number of individuals with obesity ranged from 0 to 4, indicating the frequency of obesity (BMI ≥ 25 kg/m²) over the four health examinations. The participants were categorized into five groups based on their abdominal obesity scores: 0, 1, 2, 3, and 4.

Outcome and follow-up

The primary outcome of this study was newly diagnosed cases of endometrial cancer. For this study, we created a customized database by merging the NHIS Medical Check-up database, which contains the 2009 NHIS health examination and cancer screening questionnaire results, and the NHIS claims database. Patients diagnosed with endometrial cancer were identified using the International Classification of Diseases, 10th Revision (ICD-10) code C54–55. The study population was monitored from baseline to the date of diagnosis, death, or until the end of the study period (December 31, 2020), whichever occurred first. The median follow-up duration was 7.12 (5.59–7.49) years.

Measurements and definitions of variables

Comorbidities were defined using a combination of ICD-10-CM codes and self-reported medication histories. Metabolic syndrome was defined as a combination of abdominal obesity, impaired fasting glucose, high triglyceride levels, low high-density lipoprotein (HDL) cholesterol levels, and elevated blood pressure (BP), according to the revised National Cholesterol Education Program Adult Treatment Panel III criteria [13]. Hypertension was defined as taking antihypertensive medications for at least one claim per year under ICD-10 codes I10–11, with systolic BP ≥ 140 mmHg or diastolic BP ≥ 90 mmHg. Dyslipidemia was defined as having at least one claim per year under ICD-10 code E78 for lipid-lowering agents or total cholesterol ≥ 240 mg/dL. Diabetes mellitus was defined as a fasting blood glucose level of ≥ 126 mg/dL or the presence of one or more claims per year for antihyperglycemic medications with ICD-10 code E10–14. Polycystic ovarian syndrome (PCOS) was defined as the presence of at least one claim per year under ICD-10 code E28.0–28.9 in this study. Parity was defined as childbirth using the diagnosis and procedure codes for pregnancy. Smoking status was classified as current or non-current. Heavy alcohol consumption was defined as weekly alcohol consumption of > 28 standard drinks (210 g alcohol). Regular physical activity was defined as moderate-to-high-intensity activity ≥ 3 times/week. Income levels were defined based on health insurance premiums and categorized into quartiles, with the first quartile representing the low-income group. BP was measured during regular medical checkups using standardized methods. Blood samples were collected after overnight fasting, and the parameters measured included fasting plasma glucose (FPG), total cholesterol, triglycerides, HDL cholesterol, and low-density lipoprotein (LDL) cholesterol (calculated using the Friedewald formula). The hospitals where these health examinations were performed were certified by the NHIS and subjected to regular quality control.

Statistical analysis

Baseline characteristics of the study population, divided by the number of abdominal obesity exposures, are represented as mean ± standard deviation (SD) or proportions (%). Geometric means are used for heavily skewed distributions. The disease-free probability of endometrial cancer was calculated using Kaplan–Meier curves, and the differences in the numbers of abdominal obesity exposures and general obesity exposures were analyzed using a log-rank test. The incidence rate per 1,000 person-years was estimated as the number of newly diagnosed cases of endometrial cancer during the follow-up period. Survival analyses were performed using Cox proportional hazards regression to estimate the HRs and 95% CIs for incident endometrial cancer. Adjusted models were used to adjust for potential confounding variables. Model 1 was crude. Model 2 was adjusted for age. Model 3 was adjusted for age, hypertension, dyslipidemia, diabetes, PCOS, parity, smoking status, alcohol consumption, physical activity, and low-income status. All statistical tests were two-sided at P < .05 statistical significance level. These estimations were performed using the Statistical Analysis System (SAS) statistical software package (version 9.4; SAS Institute Inc., Cary, NC, US). The data analysis was performed between February 2023 and November 2023.

Baseline characteristics of the study population

The baseline characteristics of the study population, stratified by the number of abdominal obesity exposures during the four health examinations, are represented in Table 1. Among the total study population of 445,791 young women (mean [SD] age, 34.08 [4.98] years), 386,323 (86.7%) had no abdominal obesity. A total of 31,467 (7.1%) participants had a one-time occurrence of abdominal obesity, 11,090 (2.5%) had two occurrences, 7,631 (1.7%) had three occurrences, and 9,280 (2.1%) had four consecutive occurrences of abdominal obesity. The mean WC for participants with exposure numbers of 0–4 were 69.01 ± 5.92, 80.88 ± 8.67, 85.77 ± 6.95, 89.35 ± 7, and 96.47 ± 8.16 cm, respectively. Additionally, there was a trend toward a higher prevalence of metabolic syndrome, hypertension, dyslipidemia, diabetes, PCOS, current smokers, heavy alcohol drinkers, and participants with low-income levels with increased exposure numbers. The parity decreased as the number of exposures increased. As the number of exposures increased, BMI, BP, LDL-cholesterol, triglyceride, and FPG levels showed a gradual increase, whereas HDL cholesterol levels exhibited a decrease.

Table 1

Baseline Characteristics of Young Women Stratified by Cumulative Exposure to Abdominal Obesity
	Exposure number for abdominal obesity (waist circumference ≥ 85 cm)					P for trend
	0	1	2	3	4	P for trend
No. of participants	386323	31467	11090	7631	9280	< .0001
Age, years	30.68 ± 4.55	31.55 ± 4.42	31.7 ± 4.77	31.84 ± 4.7	32 ± 4.69	< .0001
Waist circumference, cm	69.01 ± 5.92	80.88 ± 8.67	85.77 ± 6.95	89.35 ± 7	96.47 ± 8.16	< .0001
Body mass index, kg/m²	20.68 ± 2.38	24.37 ± 3.1	27.12 ± 3.06	29.07 ± 3.23	32.38 ± 4.17	< .0001
Abdominal obesity, No. (%)	0 (0)	11940 (37.94)	6911 (62.32)	6100 (79.94)	9280 (100)	< .0001
Obesity, No. (%)	20603 (5.33)	13074 (41.55)	8393 (75.68)	6979 (91.46)	9149 (98.59)	< .0001
Metabolic syndrome, No. (%)	3622 (0.94)	2745 (8.72)	2326 (20.97)	2341 (30.68)	4589 (49.45)	< .0001
Hypertension, No. (%)	4942 (1.28)	980 (3.11)	686 (6.19)	763 (10)	1691 (18.22)	< .0001
Dyslipidemia, No. (%)	13656 (3.53)	3862 (12.27)	1128 (10.17)	893 (11.7)	1426 (15.37)	< .0001
Diabetes, No. (%)	2245 (0.58)	466 (1.48)	369 (3.33)	419 (5.49)	1033 (11.13)	< .0001
Polycystic ovarian syndrome, No. (%)	3705 (0.96)	329 (1.05)	136 (1.23)	100 (1.31)	158 (1.7)	< .0001
Parity, No. (%)	29399 (7.61)	7877 (25.03)	1733 (15.63)	806 (10.56)	628 (6.77)	< .0001
Current Smoker, No. (%)	14566 (3.77)	1403 (4.46)	772 (6.96)	632 (8.28)	978 (10.54)	< .0001
Heavy alcohol drinker, No. (%)	8492 (2.2)	755 (2.4)	389 (3.51)	274 (3.59)	362 (3.9)	< .0001
Regular exercise, No. (%)	53603 (13.88)	4240 (13.47)	1768 (15.94)	1322 (17.32)	1519 (16.37)	< .0001
Low-income level, No. (%)	33108 (8.57)	3334 (10.6)	1533 (13.82)	1158 (15.17)	1545 (16.65)	< .0001
Systolic blood pressure, mmHg	110.4 ± 10.58	113.48 ± 11.62	117.49 ± 12.18	120.15 ± 12.62	124.5 ± 13.98	< .0001
Diastolic blood pressure, mmHg	69.56 ± 7.95	71.39 ± 8.61	74.08 ± 8.97	75.91 ± 9.3	78.81 ± 10.33	< .0001
Total Cholesterol, mg/dL	178.65 ± 30.05	192.06 ± 40.58	191.77 ± 35.81	193.8 ± 35.22	198.94 ± 36.18	< .0001
HDL-Cholesterol, mg/dL	65.23 ± 18.67	62 ± 18.72	57.7 ± 15.99	55.45 ± 14.26	53.02 ± 14.29	< .0001
LDL-Cholesterol, mg/dL	98.18 ± 27.65	108.4 ± 32.53	111.52 ± 33.13	114.19 ± 32.36	118.82 ± 33.36	< .0001
Triglyceride level, mg/dL^*	69.14 (69.04–69.24)	92.92 (92.33–93.5)	99.08 (98.09–100.08)	106.54 (105.27–107.82)	120.72 (119.45–122.01)	< .0001
Fasting plasma glucose, mmol/L	87.67 ± 10.77	89.2 ± 14.65	92.99 ± 21.01	95.86 ± 23.77	102.56 ± 33.84	< .0001
Median follow-up duration, years	7.13 (5.6–7.5)	7.13 (5.64–7.5)	7.07 (5.52–7.48)	7.03 (5.43–7.45)	7.01 (5.28–7.44)	< .0001
Data are represented as mean ± standard deviation (SD) for continuous variables and as proportions (%) for categorical variables.
^*Geometric mean (95% confidence interval [CI])

Risk of endometrial cancer based on exposure numbers to abdominal obesity in young women

During a median follow-up period of 7.12 years, 302 participants were newly diagnosed with endometrial cancer. In Fig. 2 (A), the cumulative incidence of endometrial cancer differed significantly according to the number of abdominal obesity exposures (log-rank test, P < .001). The incidence and HRs of endometrial cancer progressively increased with exposure to abdominal obesity (Table 2). The incidence rates of endometrial cancer were 0.08048, 0.12086, 0.20876, 0.38767, and 0.66182 per 1,000 person-years for participants with 0–4 exposures to abdominal obesity, respectively. After adjusting for age, hypertension, dyslipidemia, diabetes, PCOS, parity, smoking status, alcohol consumption, physical activity, and low income, the multivariable-adjusted HRs for incident endometrial cancer were 1.480 (95% CI, 0.970–2.258), 2.361 (95% CI, 1.391–4.008), 4.114 (95% CI, 2.546–6.647), and 6.215 (95% CI, 4.250–9.088) for participants with numbers of 1–4, respectively, compared to those with an exposure number of 0 (Table 2).

Table 2

Multivariable-adjusted Hazard Ratios for Endometrial Cancer According to Abdominal Obesity Exposure in Young Women
Exposure number	Number at risk	Incidence case	Follow-up duration (person-years)	Incidence rate (per 1,000 person-years)	HR (95% CI)
Exposure number	Number at risk	Incidence case	Follow-up duration (person-years)	Incidence rate (per 1,000 person-years)	Model 1	Model 2	Model 3
0	386323	204	2534678.47	0.08048	1 (Ref.)	1 (Ref.)	1 (Ref.)
1	31467	25	206854.47	0.12086	1.500 (0.990, 2.273)	1.417 (0.935, 2.147)	1.480 (0.970, 2.258)
2	11090	15	71851.28	0.20876	2.615 (1.548, 4.417)	2.417 (1.430, 4.085)	2.361 (1.391, 4.008)
3	7631	19	49010.5	0.38767	4.889 (3.055, 7.823)	4.482 (2.799, 7.178)	4.114 (2.546, 6.647)
4	9280	39	58928.78	0.66182	8.398 (5.962, 11.829)	7.581 (5.375, 10.693)	6.215 (4.250, 9.088)
Model 1 was crude. Model 2 is adjusted for age. Model 3 was adjusted for age, hypertension, dyslipidemia, diabetes, polycystic ovarian syndrome, parity, smoking status, alcohol consumption, physical activity, and income level.

Risk of endometrial cancer based on exposure numbers to obesity in young women

Figure 2 (B) depicts a significant difference in the cumulative incidence of endometrial cancer according to the number of obesity exposures (log-rank test, P < .001). Table 3 represents the association between the number of exposures to obesity and the risk of endometrial cancer. The incidence rates of endometrial cancer were 0.07289, 0.15727, 0.15363, 0.18126, and 0.38188 per 1,000 person-years for participants with 0–4 obesity exposures. The multivariable-adjusted HRs for incident endometrial cancer were 2.136 (95% CI, 1.354–3.371), 2.006 (95% CI, 1.116–3.605), 2.269 (95% CI, 1.313–3.919), and 4.182 (95% CI, 3.133–5.582) for participants with numbers of 1–4, respectively, compared to those with an exposure number of 0 (Table 3).

Table 3

Multivariable-adjusted Hazard Ratios for Endometrial Cancer According to Obesity Exposure in Young Women
Exposure number	Number at risk	Incidence case	Follow-up duration (person-years)	Incidence rate (per 1,000 person-years)	HR (95% CI)
Exposure number	Number at risk	Incidence case	Follow-up duration (person-years)	Incidence rate (per 1,000 person-years)	Model 1	Model 2	Model 3
0	369789	177	2428196.49	0.07289	1 (Ref.)	1 (Ref.)	1 (Ref.)
1	20385	21	133525.44	0.15727	2.163 (1.376, 3.400)	2.071 (1.317, 3.256)	2.136 (1.354, 3.371)
2	12023	12	78110.4	0.15363	2.124 (1.183, 3.810)	2.010 (1.120, 3.608)	2.006 (1.116, 3.605)
3	11911	14	77237.2	0.18126	2.508 (1.455, 4.322)	2.340 (1.357, 4.034)	2.269 (1.313, 3.919)
4	31683	78	204253.97	0.38188	5.305 (4.064, 6.925)	4.811 (3.679, 6.291)	4.182 (3.133, 5.582)
Model 1 was crude. Model 2 is adjusted for age. Model 3 was adjusted for age, hypertension, dyslipidemia, diabetes, polycystic ovarian syndrome, parity, smoking status, alcohol consumption, physical activity, and income level.

In this population-based longitudinal study, we observed a significant association between cumulative abdominal obesity exposures and the risk of endometrial cancer in young women. The analysis revealed a dose-response relationship, in which the incidence rates of endometrial cancer progressively increased with higher abdominal obesity exposures in women aged < 40 years. Furthermore, the risk of endometrial cancer based on the number of abdominal obesity exposure cases was generally higher than that based on the number of individuals with obesity. This difference became more pronounced as the number of exposures increased. These findings suggest that abdominal obesity may be a potential risk factor for the development of endometrial cancer in young women, emphasizing the need for targeted preventive interventions in at-risk populations.

Endometrial cancer in women aged < 40 is strongly associated with obesity [14,15]. Many studies have consistently demonstrated a positive correlation between elevated BMI and the risk of developing endometrial cancer [16]. However, the BMI, a crude parameter of body size, does not account for body fat composition [17]. Several studies have reported that body fat distribution confers an additional risk of endometrial cancer [18]. A previous study showed that upper body and visceral fat distributions are more closely associated with endometrial cancer risk than overall adiposity [19]. In addition, a recent epidemiological study reported that WC was more strongly associated with endometrial cancer in younger women, independent of BMI [20]. Consistent with previous research, our study indicated the cumulative impact of prolonged abdominal obesity exposure on the risk of endometrial cancer, particularly among young women, which appeared to be higher than that associated with prolonged general obesity exposure. These findings provide additional insights into the role of adiposity in the pathogenesis of endometrial cancer.

Abdominal obesity is a strong predictor of the risk of all cancers, including endometrial cancer [21]. This condition may affect the pathogenesis of endometrial cancer more than that using BMI through various mechanisms, including alterations in hormonal profiles, chronic inflammation, and insulin resistance [22]. Abdominal obesity, often accompanied by metabolic disturbances such as insulin resistance and dyslipidemia, can promote a pro-inflammatory state and alter hormone levels, particularly estrogen, thereby increasing the risk of endometrial cancer [23]. Moreover, the dysregulated secretion of adipokines and cytokines by visceral fat in individuals with abdominal obesity may contribute to inflammation, angiogenesis, cell growth, and the proliferation and progression of endometrial carcinogenesis [24]. Furthermore, lifestyle factors associated with abdominal obesity exposure, such as a high-calorie diet and sedentary behavior, may exacerbate the risk of endometrial cancer by promoting obesity-related metabolic abnormalities and chronic inflammation. Our study showed that various health conditions and lifestyle factors, such as metabolic syndrome, hypertension, dyslipidemia, diabetes, PCOS, current smoking, heavy alcohol consumption, and low-income levels, were more prevalent among young women who had higher cumulative abdominal obesity exposure. We observed the multifaceted nature of persistent abdominal obesity exposure as a risk factor for endometrial cancer, reflecting its interplay with metabolic dysfunction and unhealthy lifestyle behaviors. Further elucidation of these mechanisms could provide insights into early detection and management strategies.

The relationship between abdominal obesity and endometrial cancer is primarily attributed to hormonal and metabolic mechanisms, particularly in young adults [25]. Most young women who develop endometrial cancer have obesity, and the rate of obesity is higher among younger women than among women who are postmenopausal [26]. Prolonged exposure to unopposed estrogen, which is linked to obesity, has been implicated in the development of endometrial cancer in young women [27]. This suggests a possible link to the rising obesity epidemic in younger generations, reflecting similar trends observed in other cancers [28]. The results of the current study underscore the importance of risk stratification and preventive interventions for endometrial cancer in young women with prolonged abdominal obesity exposure. Although the incidence of endometrial cancer is lower in younger women than those who are postmenopausal, the increasing trend of endometrial cancer among the younger generation is expected to continue owing to economic development and lifestyle transitions [29]. Further etiological studies focusing on modifiable risk factors in early life are required to elucidate the causes of these emerging trends.

Despite the strengths of our study, including its population-based longitudinal design and identification of a dose-response relationship, several limitations should be considered. First, as an observational study, we examined the association between abdominal obesity and endometrial cancer but could not definitively establish reverse causality or completely explain the effects of unmeasured confounding factors such as estrogen exposure, family history, and genetic predisposition. Second, abdominal obesity was diagnosed based on a single annual health examination. However, this method is commonly used in other epidemiological studies. We addressed this limitation by counting the frequency of abdominal obesity across four consecutive health examinations. Third, we investigated uterine corpus cancer identified through the ICD-10 code as a single entity and did not further differentiate histopathologically; however, endometrial cancer accounts for approximately 90% of uterine cancers [30]. Finally, although the focus on young women is a strength, the findings may not be generalizable to populations with different demographic, ethnic, or socioeconomic characteristics, limiting the applicability of the results to diverse groups. Future prospective studies are needed to validate our findings and assess the potential effect of abdominal obesity on different subtypes of uterine cancer.

Cumulative abdominal obesity exposure in young women is associated with a progressively increased risk of endometrial cancer. In addition, abdominal obesity exposure showed a stronger association with the risk of endometrial cancer than did general obesity exposure, as cumulative exposure increased. These findings underscore the importance of identifying abdominal obesity as a potential risk factor for endometrial cancer in young women. Future research should investigate the underlying mechanisms and the potential impact of abdominal obesity exposure on different subtypes of uterine cancer to enhance risk stratification and develop effective preventive strategies.

ACKNOWLEDGEMENTS

This work was supported by the Technology Innovation Program (20008924), funded by the Ministry of Trade, Industry & Energy (MOTIE, Korea) and the National Research Foundation of Korea (NRF) grants funded by the Korean government (MSIT) (2022R1F1A061069). The funders had no role in the design and conduct of the study; the collection, management, analysis, and interpretation of the data; the preparation, review, or approval of the manuscript; or the decision to submit the manuscript for publication.

AUTHOR CONTRIBUTIONS

M.K.L. and K.D.H. contributed to the study design, analysis, and data interpretation. M.K.L. drafted and edited the manuscript. K.D.H. performed the statistical analysis of the data. M.K.L. and Y.S.S. supervised and revised the manuscript. All the authors have approved the final manuscript. M.K.L. and K.D.H. were the guarantors of this study and responsible for the integrity of the data and the accuracy of the data analysis.

COMPETING INTERESTS

The authors declare no competing financial interests in relation interests in in relation to the work.

DATA AVAILABILITY STATEMENT

Professor Han had full access to all the data in the study and took responsibility for the integrity of the data and the accuracy of the data analysis. The authors are restricted from sharing the data underlying this study because the Korean National Health Insurance Service (NHIS) owns the data. Researchers can request access to the NHIS website (https://nhiss.nhis.or.kr). The details of this process and a provisional guide are available at http://nhiss.nhis.or.kr/bd/ab/bdaba000eng.do.

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Cumulative abdominal obesity exposure and risk of endometrial cancer in young women: a population-based cohort study

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Abstract

BACKGROUND

METHODS

RESULTS

CONCLUSION

Figures

What’s new?

INTRODUCTION

METHODS

Data sources

Study population

Cumulative abdominal obesity exposure

Outcome and follow-up

Measurements and definitions of variables

Statistical analysis

RESULTS

Baseline characteristics of the study population

Risk of endometrial cancer based on exposure numbers to abdominal obesity in young women

Risk of endometrial cancer based on exposure numbers to obesity in young women

DISCUSSION

CONCLUSION

Declarations

References

Additional Declarations

Status:

Version 1