This article is featured in Highlights of This Issue, p. 983

Uterine corpus cancer is the most common invasive gynecologic cancer among U.S. women. Studies of endometrial cancers, which comprise approximately 90% of all uterine cancers, have identified numerous risk factors, many of which appear to reflect high levels of estrogens in the absence of sufficient progesterone. Recent advances have indicated that the disease is etiologically heterogeneous, consisting of at least two major subgroups. This heterogeneity extends to important racial differences in both incidence and survival, possibly partially attributable to genetic factors.

Uterine cancer incidence is highest in North America and Northern Europe, intermediate in Southern Europe and temperate South America, and lowest in Southern and Eastern Asia and most of Africa (Fig. 1; ref. 1). This likely reflects prevalence differences in risk factors, including obesity and reproductive patterns. In the United States, uterine cancer is the fourth most frequently diagnosed cancer, with estimates of 63,230 diagnoses in 2018 (lifetime risk of 1 out of every 40 women; ref. 2). The average annual age-adjusted incidence of uterine cancer from the Surveillance, Epidemiology and End Results Program (SEER) was 25.7 per 100,000 women between 2010 and 2014 (3). The disease is rare before the age of 45 years, but risk rises sharply among women of all races in their late 40s to middle 60s (Fig. 2). Worldwide, uterine cancer ranked in 2012 as the sixth most common cancer, with 319,600 estimated cases (4).

Figure 1.

Age-standardized incidence rates for corpus uteri cancer. Figure 1 shows age-standardized incidence rates for corpus uteri cancer using data from GLOBOCAN, 2012. Uterine cancer incidence is highest in North America and Northern Europe, intermediate in Southern Europe and temperate South America, and lowest in Southern and Eastern Asia and most of Africa.

Figure 1.

Age-standardized incidence rates for corpus uteri cancer. Figure 1 shows age-standardized incidence rates for corpus uteri cancer using data from GLOBOCAN, 2012. Uterine cancer incidence is highest in North America and Northern Europe, intermediate in Southern Europe and temperate South America, and lowest in Southern and Eastern Asia and most of Africa.

Close modal
Figure 2.

Age-specific uterine cancer incidence rates. Figure 2 shows age-specific uterine cancer incidence rates among non-Hispanic white, Hispanic white, black, American Indian/Alaskan Native, and Asian/Pacific Islander U.S. women using data from the SEER Program (SEER-18, 2003–2014).

Figure 2.

Age-specific uterine cancer incidence rates. Figure 2 shows age-specific uterine cancer incidence rates among non-Hispanic white, Hispanic white, black, American Indian/Alaskan Native, and Asian/Pacific Islander U.S. women using data from the SEER Program (SEER-18, 2003–2014).

Close modal

Dramatic changes in the incidence of uterine cancers have occurred over time. A marked increase in U.S. incidence peaked around 1975, a trend later linked with the widespread use of menopausal estrogens in the late 1960s and early 1970s (Fig. 3). After a subsequent period of steady or declining incidence rates in many countries, endometrial cancer is again on the rise, mirroring increases in obesity prevalence (4, 5).

Figure 3.

Trends in uterine cancer incidence and mortality. Figure 3 shows trends in uterine cancer incidence and mortality among white and black U.S. women using data from the SEER Program (SEER-9, 1973–2014).

Figure 3.

Trends in uterine cancer incidence and mortality. Figure 3 shows trends in uterine cancer incidence and mortality among white and black U.S. women using data from the SEER Program (SEER-9, 1973–2014).

Close modal

In the United States, age-adjusted mortality is 4.6 per 100,000 women, whereas in Europe, mortality ranges between 2 and 4 per 100,000 (refs. 3, 6; Fig. 4). Similar to recent incidence increases, endometrial cancer mortality rates are also on the rise (4, 7). Overall, 5-year survival is approximately 82%, which represents a marked increase since the 1960s when it was 60% (8, 9). The distribution of uterine cancer stage, a strong prognostic factor, has remained stable (8, 10–12). Five-year survival is 95.3% for localized, 67.5% for regional, and 16.9% for distant-stage diseases (9).

Figure 4.

Age-standardized mortality rates for corpus uteri cancer. Figure 4 shows age-standardized mortality rates for corpus uteri cancer using data from GLOBOCAN, 2012. In the United States, age-adjusted mortality is 4.6 per 100,000 women, whereas in Europe, mortality ranges between 2 and 4 per 100,000.

Figure 4.

Age-standardized mortality rates for corpus uteri cancer. Figure 4 shows age-standardized mortality rates for corpus uteri cancer using data from GLOBOCAN, 2012. In the United States, age-adjusted mortality is 4.6 per 100,000 women, whereas in Europe, mortality ranges between 2 and 4 per 100,000.

Close modal

Historically, endometrial cancer incidence was lower among black compared with white women; however, that gap has narrowed significantly over time (13–17). Moreover, once hysterectomy rates are taken into account, incidence in blacks surpasses that of whites (18). Although the associations for established endometrial cancer risk factors among black and white women are similar (19), prevalence differences may partially explain the markedly higher incidence increases among blacks. Endometrial cancer mortality is twice as high among black compared with white women (8.1 vs. 4.2 per 100,000 women) and has been attributed to aggressive clinical characteristics, lower socioeconomic status, higher prevalence of comorbid conditions, poor patient–provider interactions, and inferior treatment (20). Although less frequently studied, Asian and Hispanic women have lower risks of endometrial cancer compared with white women; however, 5-year survival is the same or better (17, 21).

Metabolic factors

A strong risk factor for endometrial cancer is obesity, accounting for 40% to 50% of all U.S. cases (refs. 22, 23; see Table 1 and Fig. 5). Overall body size appears to be more important than body fat distribution (24). Women with obesity-associated diseases such as diabetes (25, 26), hypertension (27), and polycystic ovary syndrome (28) are also at elevated risk, although obesity may contribute to these relationships. Metabolic syndrome has also been associated with significant risk elevations, although to a lesser extent than obesity (29).

Table 1.

Summary of risk factors, candidate genes, and serum biomarkers associated with endometrial cancer risk

DomainFactorEstimated relative riskHeterogeneity of riskCommentsHighest level of evidenceRefs.
Metabolic factors Obesity 2.0–5.0 Association stronger for type I than II cancers Each 5 kg/m2 increase in BMI is associated with a 62% increased risk Cohort study (22, 83) 
 Diabetes 2.0 No heterogeneity observed Uncertain extent to which relations are confounded by obesity Meta-analysis of cohort studies (26, 83) 
 Hypertension 1.1–1.3 Not examined Association between hypertension and endometrial cancer was weaker, but still significant, among studies with adjustment for BMI Meta-analysis of case–control and cohort studies (27) 
 Metabolic syndrome 1.4–2.0 No heterogeneity observed Adjustment for overweight/obesity does not eliminate increased risks associated with metabolic syndrome factors Meta-analysis of case–control and cohort studies (29, 114) 
 Polycystic ovary syndrome 2.8 Not examined Uncertain extent to which relations are confounded by obesity Meta-analysis of case–control studies (28) 
Reproductive factors Nulliparity 3.0 Association restricted to type I cancers Further reductions for multiparous women Meta-analysis of case–control and cohort studies (30, 31) 
 Infertility 1.8 No heterogeneity observed Even after adjusting for nulliparity, infertile women had increased risk Pooled analysis of case–control and cohort studies (32) 
 Young age at menarche 1.5–2.0 No heterogeneity observed 4% reduction in risk per 2 years delay in menarcheal age Meta-analysis of cohort studies (33, 86) 
 Old age at natural menopause 1.5–2.2 No heterogeneity observed Pronounced risks among nonusers of menopausal hormones Cohort studies (30, 86) 
 Breastfeeding 0.9 No heterogeneity observed Greatest reductions for long-term breastfeeding Pooled analysis of case–control and cohort studies (36) 
Contraceptives Combination oral contraceptives 0.3–0.5 No heterogeneity observed Risk reduction persists for > 30 years Pooled analysis of case–control and cohort studies (83, 86) 
 Intrauterine device use 0.5–0.8 Association stronger for type I than II cancers More studies needed on the effects of progestin-releasing devices Pooled analysis of case–control and cohort studies (37, 38) 
Menopausal hormone therapy Menopausal estrogens 10.0–20.0 Not examined Highest risks for long-term and high-dose users of unopposed estrogens Cohort study (39) 
 Menopausal estrogen plus progestins 0.7 Association stronger for type I than II cancers Risk reduction is greatest for obese women Randomized trial (39, 42, 43) 
Tamoxifen use High cumulative doses of tamoxifen 2.2 Nonendometrioid histology subtypes appear to be especially affected by tamoxifen Endometrial cancer risks highest shortly after exposure Randomized trial (44, 45) 
Lifestyle factors Cigarette smoking 0.5 No heterogeneity observed Effects of cigarette smoking are particularly strong among postmenopausal women and menopausal hormone users Meta-analysis of case–control and cohort studies (47, 87) 
 Moderate-to-vigorous physical activity 0.8 No heterogeneity observed Inverse relation with physical activity restricted to overweight or obese women Meta-analysis of case–control and cohort studies (49, 50, 90) 
Family history Family history 1.8 No heterogeneity observed Association is independent of Lynch syndrome status Meta-analysis of case–control and cohort studies (75, 76) 
High penetrance gene mutations MLH1 18%–54% lifetime risk Not examined   (77–79) 
 MSH2 21%–49% lifetime risk Not examined   (77–79) 
 MSH6 16%–61% lifetime risk Not examined   (78, 79) 
 PMS2 12% lifetime risk Not examined   (80) 
 EPCAM 12% lifetime risk Not examined   (81) 
Low and moderate penetrance genes  1.1–1.4 Some SNP associations differ according to histology   (86) 
Serum biomarkers Estradiol and other endogenous estrogens 2.0–6.2 Some support for stronger relations with type I than II cancers Associations persist after adjustment for body mass and show slightly stronger relations for type I than II cancers  (97) 
 Insulin Significant mean difference between endometrial cancer cases and controls: 33.94 Not examined This meta-analysis did not detect an association among studies restricted to postmenopausal women, possibly due to small numbers  (99) 
 C-peptide Significant mean difference between endometrial cancer cases and controls: 0.14 Not examined A lack of information on fasting time since the last meal may have led to misclassification of C-peptide levels  (99) 
 Androgen Postmenopausal: 1.7 Similar associations observed when restricted to women with type I Higher circulating levels of androgens are associated with endometrial cancer among postmenopausal women  (93–95, 97, 98) 
  Premenopausal: 0.9     
 Inflammatory markers SERPINE1: 2.4 No heterogeneity observed although the number of women with type II was small Endometrial cancer risk was most pronounced among obese women with the highest inflammation score  (102) 
  VEGF-A: 2.6     
  Anti-inflammatory cytokines (IL13, IL21): 0.5–0.6     
  Proinflammatory cytokines (CCL3, IL1B, IL23): 0.5–0.6     
 Adiponectin 0.5 Not examined Inverse associations were strongest among postmenopausal women, nulliparous women, and nonhormone users  (103) 
 Leptin 2.2 Not examined Associations were strongest among nonhormone users, diabetic women, and in prospective studies  (103) 
DomainFactorEstimated relative riskHeterogeneity of riskCommentsHighest level of evidenceRefs.
Metabolic factors Obesity 2.0–5.0 Association stronger for type I than II cancers Each 5 kg/m2 increase in BMI is associated with a 62% increased risk Cohort study (22, 83) 
 Diabetes 2.0 No heterogeneity observed Uncertain extent to which relations are confounded by obesity Meta-analysis of cohort studies (26, 83) 
 Hypertension 1.1–1.3 Not examined Association between hypertension and endometrial cancer was weaker, but still significant, among studies with adjustment for BMI Meta-analysis of case–control and cohort studies (27) 
 Metabolic syndrome 1.4–2.0 No heterogeneity observed Adjustment for overweight/obesity does not eliminate increased risks associated with metabolic syndrome factors Meta-analysis of case–control and cohort studies (29, 114) 
 Polycystic ovary syndrome 2.8 Not examined Uncertain extent to which relations are confounded by obesity Meta-analysis of case–control studies (28) 
Reproductive factors Nulliparity 3.0 Association restricted to type I cancers Further reductions for multiparous women Meta-analysis of case–control and cohort studies (30, 31) 
 Infertility 1.8 No heterogeneity observed Even after adjusting for nulliparity, infertile women had increased risk Pooled analysis of case–control and cohort studies (32) 
 Young age at menarche 1.5–2.0 No heterogeneity observed 4% reduction in risk per 2 years delay in menarcheal age Meta-analysis of cohort studies (33, 86) 
 Old age at natural menopause 1.5–2.2 No heterogeneity observed Pronounced risks among nonusers of menopausal hormones Cohort studies (30, 86) 
 Breastfeeding 0.9 No heterogeneity observed Greatest reductions for long-term breastfeeding Pooled analysis of case–control and cohort studies (36) 
Contraceptives Combination oral contraceptives 0.3–0.5 No heterogeneity observed Risk reduction persists for > 30 years Pooled analysis of case–control and cohort studies (83, 86) 
 Intrauterine device use 0.5–0.8 Association stronger for type I than II cancers More studies needed on the effects of progestin-releasing devices Pooled analysis of case–control and cohort studies (37, 38) 
Menopausal hormone therapy Menopausal estrogens 10.0–20.0 Not examined Highest risks for long-term and high-dose users of unopposed estrogens Cohort study (39) 
 Menopausal estrogen plus progestins 0.7 Association stronger for type I than II cancers Risk reduction is greatest for obese women Randomized trial (39, 42, 43) 
Tamoxifen use High cumulative doses of tamoxifen 2.2 Nonendometrioid histology subtypes appear to be especially affected by tamoxifen Endometrial cancer risks highest shortly after exposure Randomized trial (44, 45) 
Lifestyle factors Cigarette smoking 0.5 No heterogeneity observed Effects of cigarette smoking are particularly strong among postmenopausal women and menopausal hormone users Meta-analysis of case–control and cohort studies (47, 87) 
 Moderate-to-vigorous physical activity 0.8 No heterogeneity observed Inverse relation with physical activity restricted to overweight or obese women Meta-analysis of case–control and cohort studies (49, 50, 90) 
Family history Family history 1.8 No heterogeneity observed Association is independent of Lynch syndrome status Meta-analysis of case–control and cohort studies (75, 76) 
High penetrance gene mutations MLH1 18%–54% lifetime risk Not examined   (77–79) 
 MSH2 21%–49% lifetime risk Not examined   (77–79) 
 MSH6 16%–61% lifetime risk Not examined   (78, 79) 
 PMS2 12% lifetime risk Not examined   (80) 
 EPCAM 12% lifetime risk Not examined   (81) 
Low and moderate penetrance genes  1.1–1.4 Some SNP associations differ according to histology   (86) 
Serum biomarkers Estradiol and other endogenous estrogens 2.0–6.2 Some support for stronger relations with type I than II cancers Associations persist after adjustment for body mass and show slightly stronger relations for type I than II cancers  (97) 
 Insulin Significant mean difference between endometrial cancer cases and controls: 33.94 Not examined This meta-analysis did not detect an association among studies restricted to postmenopausal women, possibly due to small numbers  (99) 
 C-peptide Significant mean difference between endometrial cancer cases and controls: 0.14 Not examined A lack of information on fasting time since the last meal may have led to misclassification of C-peptide levels  (99) 
 Androgen Postmenopausal: 1.7 Similar associations observed when restricted to women with type I Higher circulating levels of androgens are associated with endometrial cancer among postmenopausal women  (93–95, 97, 98) 
  Premenopausal: 0.9     
 Inflammatory markers SERPINE1: 2.4 No heterogeneity observed although the number of women with type II was small Endometrial cancer risk was most pronounced among obese women with the highest inflammation score  (102) 
  VEGF-A: 2.6     
  Anti-inflammatory cytokines (IL13, IL21): 0.5–0.6     
  Proinflammatory cytokines (CCL3, IL1B, IL23): 0.5–0.6     
 Adiponectin 0.5 Not examined Inverse associations were strongest among postmenopausal women, nulliparous women, and nonhormone users  (103) 
 Leptin 2.2 Not examined Associations were strongest among nonhormone users, diabetic women, and in prospective studies  (103) 
Figure 5.

Magnitude of association of endometrial cancer risk factors. Figure 5 contains a summary of the magnitude of association for established endometrial cancer risk factors. Risks are approximate and can vary depending on the extent of exposure.

Figure 5.

Magnitude of association of endometrial cancer risk factors. Figure 5 contains a summary of the magnitude of association for established endometrial cancer risk factors. Risks are approximate and can vary depending on the extent of exposure.

Close modal

Reproductive factors

Nulliparous women are at substantially higher risks than parous women (30, 31), with infertility additionally contributing to risk (32). Other established reproductive risk factors include young ages at menarche and/or old ages at menopause (30, 33), potentially reflecting increased numbers of lifetime ovulatory cycles (34). Breastfeeding has also recently emerged as a possible protective factor (35, 36).

Contraceptives

The use of combination oral contraceptives has been linked with marked risk reductions which persist for more than 30 years after discontinuation. Intrauterine devices also appear to reduce endometrial cancer risk (37, 38).

Menopausal hormone therapy

Menopausal hormones have been strongly linked with risk increases, particularly for extended usage of high-dose unopposed estrogens (39). Progestins cause regression of estrogen-induced endometrial hyperplasia, the presumed precursor of most endometrial cancers (40), leading to estrogens commonly being prescribed with a progestin (particularly among nonhysterectomized women). Sequential progestin use, i.e., <10 days per month, is associated with only slight risk reductions compared with unopposed estrogen use (41). However, continuous combination therapy reduces risk compared with nonhormone usage (39, 42). Associations of hormone usage are strongly modified by body mass index (BMI; refs. 39, 43).

Tamoxifen use

Clinical trials have demonstrated increased endometrial cancer risk among tamoxifen-treated breast cancer patients, with risks highest shortly after exposure, among those receiving high cumulative doses, and for histologies usually associated with a poor prognosis (44, 45).

Lifestyle factors

Cigarette smoking (46, 47) and moderate-to-active physical activity levels (48–50) have been associated with reduced risks, relations that are independent of other risk factors, including obesity.

Other factors

It remains less clear whether risk reductions associated with high levels of fruit and vegetable consumption and/or of micronutrients are independent risk factors (51–54). Higher dairy product intake (55), coffee consumption (56), and consumption of green, but not black, tea (57) may lead to risk reductions. High-fat diets (53, 54) and alcohol consumption (58) have not generally been associated with risk. Use of the antidiabetic drug metformin (59) or aspirin (60) appears to slightly reduce risk.

Controversial risk factors

Less accepted as potential risk factors are several occupational exposures (61, 62); talcum powder use (63–65); thyroid diseases, cholecystectomy and endometriosis (66–68); antidepressants, statins, and acetaminophen (69–71); endocrine disruptors (72); tubal ligation (73); and electromagnetic radiation (74).

Familial and genetic factors

Elevated endometrial cancer risks have been noted among women with a first-degree family history of endometrial cancer (75, 76). This could reflect familial obesity (genetic or environment) or inherited risk, such as Lynch syndrome, an autosomal-dominant cancer predisposition syndrome attributed to germline mutations in one of several mismatch repair genes. Specific mutations have been estimated to result in cumulative lifetime endometrial cancer risks ranging between 12% and 61% (77–81), with MSH6 showing the highest risks (ref. 82; Table 1). However, the higher range estimates may reflect reliance on data from clinical cancer genetic cohorts that are biased to include patients with family histories of cancer. Although Lynch syndrome is associated with a high cumulative lifetime risk of endometrial cancer, the relative rarity of the condition translates to an attributable fraction of only 5%.

The genome-wide association study approach has identified 17 risk loci for endometrial cancer, including 9 recently identified loci (83), which are modestly associated with risk (ORs, 0.8–1.4). Some risk loci are significant only for endometrioid cancers. Few rare variants have been identified through exome-wide association studies (84), but candidate gene studies (85, 86) have identified a number of SNPs in genes that may possibly affect risk.

Important heterogeneity has been noted between type I (predominantly endometrioid adenocarcinomas with a hormonally driven etiology) and type II (mainly nonendometrioid malignancies that occur frequently among older and nonwhite women) cancers (see Tables 1 and 2). Several epidemiologic studies have found that type II cancers are less strongly linked to classic risk factors, such as obesity, nulliparity, and hormones (44, 87).

Stronger relationships of hormonal, reproductive, and anthropometric risk factors have been found for endometrioid endometrial cancers compared with serous, clear cell, mucinous, or mixed epithelial tumors (44, 87–91). Furthermore, The Cancer Genome Atlas (TCGA) study has identified four molecular subtypes of endometrial cancer: polymerase ϵ (POLE) ultramutated, microsatellite instability hypermutated, copy-number low, and copy-number high clusters (92). A comprehensive evaluation of endometrial cancer risk factors according to TCGA subtype has not yet been conducted.

Estrogens are strongly related to risk (Table 1; refs. 93–95), with one study showing generalized uterotropic activity of both parent estrogens and metabolites (96). Circulating androgens, the main source of estrogens in postmenopausal women, have also been linked with increased risk (93–95, 97, 98). Consistent with an association between diabetes and endometrial cancer risk, insulin and c-peptide have been demonstrated to be elevated among women with endometrial cancer (99). Insulin-like growth factor 1 (IGF)-1 and the IGF-binding proteins are less consistently linked with risk (100, 101). Risk has also been related to circulating levels of inflammatory biomarkers (102) and with several obesity-related hormones (103).

Two risk prediction models, one developed in U.S.-based cohorts (104) and the other in a European cohort (105), demonstrated moderate discriminatory ability for established endometrial cancer risk factors (respective discrimination assessed by the area under the curve of 0.68 and 0.77). In the latter model, the addition of prediagnostic serum biomarkers only modestly (1.7%) increased discrimination (106).

Projection models indicate that endometrial cancer incidence will continue to rise, mainly as a consequence of rising obesity prevalence (7, 107). Changes in the distribution of other endometrial cancer risk factors also contribute to the projected growth in incidence, including increases in diabetes and metabolic syndrome (108, 109), declines in use of combination hormone therapy (5), and decreases in childbearing and smoking (110, 111). Moreover, hysterectomy for benign conditions has declined in recent decades, particularly among whites, contributing to more at-risk women (18, 112). In the next decade, mortality rates are also projected to increase (113).

Primary prevention efforts focused on weight loss or use of medications are attractive prevention strategies. For high-risk patients, bariatric surgery is associated with a 44% reduced risk of developing endometrial cancer (114). Among Lynch syndrome patients, there is some evidence that oral contraceptive use may reduce risk (115).

Endometrial cancer screening is not recommended for women in the general population (116). Studies evaluating the use of endometrial biopsy and/or transvaginal ultrasound have generally shown low detection specificity (117). Nonetheless, the American Cancer Society recommends annual screening for Lynch syndrome patients with endometrial biopsy beginning at age 35 years. Development of early detection blood-based biomarkers is being explored (118).

Although considered an indolent tumor, the rapid increase in both endometrial cancer incidence and mortality warrants additional etiologic and prevention research. Although progress has been made in identifying risk factors for the most common endometrial cancer subtype, this has not translated into effective primary prevention strategies. Future efforts should be directed at reducing the prevalence of modifiable risk factors (e.g., obesity). Additional research is needed to identify risk factors for aggressive endometrial cancer subtypes, particularly among black women.

To favorably affect survival, research on screening modalities to identify endometrial cancer at early stages is needed. Currently, screening in the general population is not recommended, but efforts to identify high-risk women could be beneficial.

No potential conflicts of interest were disclosed.

Conception and design: A.S. Felix, L.A. Brinton

Development of methodology: A.S. Felix, L.A. Brinton

Acquisition of data (provided animals, acquired and managed patients, provided facilities, etc.): A.S. Felix, L.A. Brinton

Analysis and interpretation of data (e.g., statistical analysis, biostatistics, computational analysis): A.S. Felix, L.A. Brinton

Writing, review, and/or revision of the manuscript: A.S. Felix, L.A. Brinton

Administrative, technical, or material support (i.e., reporting or organizing data, constructing databases): A.S. Felix, L.A. Brinton

Study supervision: A.S. Felix, L.A. Brinton

1.
Ferlay
J
,
Soerjomataram
I
,
Ervik
M
,
Dikshit
R
,
Eser
S
,
Mathers
C
, et al
GLOBOCAN 2012 v1.0, cancer incidence and mortality worldwide: IARC CancerBase No. 11 [Internet]
.
[cited 2018 Apr 7]. Available from:
http://globocan.iarc.fr/Default.aspx.
Lyon, France
:
International Agency for Research on Cancer
. 
2013
.
2.
Siegel
RL
,
Miller
KD
,
Jemal
A
. 
Cancer statistics, 2018
.
CA Cancer J Clin
2018
;
68
:
7
30
.
3.
Siegel
RL
,
Miller
KD
,
Jemal
A
. 
Cancer statistics, 2017
.
CA Cancer J Clin
2017
;
67
:
7
30
.
4.
Torre
LA
,
Islami
F
,
Siegel
RL
,
Ward
EM
,
Jemal
A
. 
Global cancer in women: burden and trends
.
Cancer Epidemiol Biomarkers Prev
2017
;
26
:
444
57
.
5.
Wartko
P
,
Sherman
ME
,
Yang
HP
,
Felix
AS
,
Brinton
LA
,
Trabert
B
. 
Recent changes in endometrial cancer trends among menopausal-age U.S. women
.
Cancer Epidemiol
2013
;
37
:
374
7
.
6.
Weiderpass
E
,
Antoine
J
,
Bray
FI
,
Oh
JK
,
Arbyn
M
. 
Trends in corpus uteri cancer mortality in member states of the European Union
.
Eur J Cancer
2014
;
50
:
1675
84
.
7.
Rahib
L
,
Smith
BD
,
Aizenberg
R
,
Rosenzweig
AB
,
Fleshman
JM
,
Matrisian
LM
. 
Projecting cancer incidence and deaths to 2030: the unexpected burden of thyroid, liver, and pancreas cancers in the United States
.
Cancer Res
2014
;
74
:
2913
21
.
8.
Creasman
WT
,
Odicino
F
,
Maisonneuve
P
,
Quinn
MA
,
Beller
U
,
Benedet
JL
, et al
Carcinoma of the corpus uteri. FIGO 26th Annual Report on the results of treatment in gynecological cancer
.
Int J Gynaecol Obstet
2006
;
95
Suppl 1
:
S105
43
.
9.
DeSantis
CE
,
Lin
CC
,
Mariotto
AB
,
Siegel
RL
,
Stein
KD
,
Kramer
JL
, et al
Cancer treatment and survivorship statistics, 2014
.
CA Cancer J Clin
2014
;
64
:
252
71
.
10.
Ueda
SM
,
Kapp
DS
,
Cheung
MK
,
Shin
JY
,
Osann
K
,
Husain
A
, et al
Trends in demographic and clinical characteristics in women diagnosed with corpus cancer and their potential impact on the increasing number of deaths
.
Am J Obstet Gynecol
2008
;
198
:
218
e1–6
.
11.
Creasman
WT
,
Ali
S
,
Mutch
DG
,
Zaino
RJ
,
Powell
MA
,
Mannel
RS
, et al
Surgical-pathological findings in type 1 and 2 endometrial cancer: an NRG Oncology/Gynecologic Oncology Group study on GOG-210 protocol
.
Gynecol Oncol
2017
;
145
:
519
25
.
12.
Wright
JD
,
Fiorelli
J
,
Schiff
PB
,
Burke
WM
,
Kansler
AL
,
Cohen
CJ
, et al
Racial disparities for uterine corpus tumors: changes in clinical characteristics and treatment over time
.
Cancer
2009
;
115
:
1276
85
.
13.
Farley
J
,
Risinger
JI
,
Rose
GS
,
Maxwell
GL
. 
Racial disparities in blacks with gynecologic cancers
.
Cancer
2007
;
110
:
234
43
.
14.
Allard
JE
,
Maxwell
GL
. 
Race disparities between black and white women in the incidence, treatment, and prognosis of endometrial cancer
.
Cancer Control
2009
;
16
:
53
6
.
15.
Long
B
,
Liu
FW
,
Bristow
RE
. 
Disparities in uterine cancer epidemiology, treatment, and survival among African Americans in the United States
.
Gynecol Oncol
2013
;
130
:
652
9
.
16.
Collins
Y
,
Holcomb
K
,
Chapman-Davis
E
,
Khabele
D
,
Farley
JH
. 
Gynecologic cancer disparities: a report from the Health Disparities Taskforce of the Society of Gynecologic Oncology
.
Gynecol Oncol
2014
;
133
:
353
61
.
17.
Cote
ML
,
Ruterbusch
JJ
,
Olson
SH
,
Lu
K
,
Ali-Fehmi
R
. 
The growing burden of endometrial cancer: a major racial disparity affecting black women
.
Cancer Epidemiol Biomarkers Prev
2015
;
24
:
1407
15
.
18.
Jamison
PM
,
Noone
AM
,
Ries
LA
,
Lee
NC
,
Edwards
BK
. 
Trends in endometrial cancer incidence by race and histology with a correction for the prevalence of hysterectomy, SEER 1992 to 2008
.
Cancer Epidemiol Biomarkers Prev
2013
;
22
:
233
41
.
19.
Cote
ML
,
Alhajj
T
,
Ruterbusch
JJ
,
Bernstein
L
,
Brinton
LA
,
Blot
WJ
, et al
Risk factors for endometrial cancer in black and white women: a pooled analysis from the Epidemiology of Endometrial Cancer Consortium (E2C2)
.
Cancer Causes Control
2015
;
26
:
287
96
.
20.
Morris
AM
,
Rhoads
KF
,
Stain
SC
,
Birkmeyer
JD
. 
Understanding racial disparities in cancer treatment and outcomes
.
J Am Coll Surg
2010
;
211
:
105
13
.
21.
Setiawan
VW
,
Pike
MC
,
Kolonel
LN
,
Nomura
AM
,
Goodman
MT
,
Henderson
BE
. 
Racial/ethnic differences in endometrial cancer risk: the multiethnic cohort study
.
Am J Epidemiol
2007
;
165
:
262
70
.
22.
Bhaskaran
K
,
Douglas
I
,
Forbes
H
,
dos-Santos-Silva
I
,
Leon
DA
,
Smeeth
L
. 
Body-mass index and risk of 22 specific cancers: a population-based cohort study of 5.24 million UK adults
.
Lancet
2014
;
384
:
755
65
.
23.
Onstad
MA
,
Schmandt
RE
,
Lu
KH
. 
Addressing the role of obesity in endometrial cancer risk, prevention, and treatment
.
J Clin Oncol
2016
;
34
:
4225
30
.
24.
Ju
W
,
Kim
HJ
,
Hankinson
SE
,
De Vivo
I
,
Cho
E
. 
Prospective study of body fat distribution and the risk of endometrial cancer
.
Cancer Epidemiol
2015
;
39
:
567
70
.
25.
Tsilidis
KK
,
Kasimis
JC
,
Lopez
DS
,
Ntzani
EE
,
Ioannidis
JP
. 
Type 2 diabetes and cancer: umbrella review of meta-analyses of observational studies
.
BMJ
2015
;
350
:
g7607
.
26.
Liao
C
,
Zhang
D
,
Mungo
C
,
Andrew Tompkins
D
,
Zeidan
AM
. 
Is diabetes mellitus associated with increased incidence and disease-specific mortality in endometrial cancer? A systematic review and meta-analysis of cohort studies
.
Gynecol Oncol
2014
;
135
:
163
71
.
27.
Aune
D
,
Sen
A
,
Vatten
LJ
. 
Hypertension and the risk of endometrial cancer: a systematic review and meta-analysis of case-control and cohort studies
.
Sci Rep
2017
;
7
:
44808
.
28.
Barry
JA
,
Azizia
MM
,
Hardiman
PJ
. 
Risk of endometrial, ovarian and breast cancer in women with polycystic ovary syndrome: a systematic review and meta-analysis
.
Hum Reprod Update
2014
;
20
:
748
58
.
29.
Esposito
K
,
Chiodini
P
,
Capuano
A
,
Bellastella
G
,
Maiorino
MI
,
Giugliano
D
. 
Metabolic syndrome and endometrial cancer: a meta-analysis
.
Endocrine
2014
;
45
:
28
36
.
30.
Dossus
L
,
Allen
N
,
Kaaks
R
,
Bakken
K
,
Lund
E
,
Tjonneland
A
, et al
Reproductive risk factors and endometrial cancer: the European prospective investigation into cancer and nutrition
.
Int J Cancer
2010
;
127
:
442
51
.
31.
Wu
QJ
,
Li
YY
,
Tu
C
,
Zhu
J
,
Qian
KQ
,
Feng
TB
, et al
Parity and endometrial cancer risk: a meta-analysis of epidemiological studies
.
Sci Rep
2015
;
5
:
14243
.
32.
Yang
HP
,
Cook
LS
,
Weiderpass
E
,
Adami
HO
,
Anderson
KE
,
Cai
H
, et al
Infertility and incident endometrial cancer risk: a pooled analysis from the Epidemiology of Endometrial Cancer Consortium (E2C2)
.
Br J Cancer
2015
;
112
:
925
33
.
33.
Gong
TT
,
Wang
YL
,
Ma
XX
. 
Age at menarche and endometrial cancer risk: a dose-response meta-analysis of prospective studies
.
Sci Rep
2015
;
5
:
14051
.
34.
Yang
HP
,
Murphy
KR
,
Pfeiffer
RM
,
George
N
,
Garcia-Closas
M
,
Lissowska
J
, et al
Lifetime number of ovulatory cycles and risks of ovarian and endometrial cancer among postmenopausal women
.
Am J Epidemiol
2016
;
183
:
800
14
.
35.
Jordan
SJ
,
Na
R
,
Johnatty
SE
,
Wise
LA
,
Adami
HO
,
Brinton
LA
, et al
Breastfeeding and endometrial cancer risk: an analysis from the epidemiology of endometrial cancer consortium
.
Obstet Gynecol
2017
;
129
:
1059
67
.
36.
Zhan
B
,
Liu
X
,
Li
F
,
Zhang
D
. 
Breastfeeding and the incidence of endometrial cancer: a meta-analysis
.
Oncotarget
2015
;
6
:
38398
409
.
37.
Felix
AS
,
Gaudet
MM
,
La Vecchia
C
,
Nagle
CM
,
Shu
XO
,
Weiderpass
E
, et al
Intrauterine devices and endometrial cancer risk: a pooled analysis of the Epidemiology of Endometrial Cancer Consortium
.
Int J Cancer
2015
;
136
:
E410
22
.
38.
Beining
RM
,
Dennis
LK
,
Smith
EM
,
Dokras
A
. 
Meta-analysis of intrauterine device use and risk of endometrial cancer
.
Ann Epidemiol
2008
;
18
:
492
9
.
39.
Beral
V
,
Bull
D
,
Reeves
G
,
Million Women Study
C
. 
Endometrial cancer and hormone-replacement therapy in the Million Women Study
.
Lancet
2005
;
365
:
1543
51
.
40.
Lacey
JV
 Jr
,
Sherman
ME
,
Rush
BB
,
Ronnett
BM
,
Ioffe
OB
,
Duggan
MA
, et al
Absolute risk of endometrial carcinoma during 20-year follow-up among women with endometrial hyperplasia
.
J Clin Oncol
2010
;
28
:
788
92
.
41.
Razavi
P
,
Pike
MC
,
Horn-Ross
PL
,
Templeman
C
,
Bernstein
L
,
Ursin
G
. 
Long-term postmenopausal hormone therapy and endometrial cancer
.
Cancer Epidemiol Biomarkers Prev
2010
;
19
:
475
83
.
42.
Chlebowski
RT
,
Anderson
GL
,
Sarto
GE
,
Haque
R
,
Runowicz
CD
,
Aragaki
AK
, et al
Continuous combined estrogen plus progestin and endometrial cancer: the Women's Health Initiative Randomized Trial
.
J Natl Cancer Inst
2016
;
108
.
43.
Trabert
B
,
Wentzensen
N
,
Yang
HP
,
Sherman
ME
,
Hollenbeck
AR
,
Park
Y
, et al
Is estrogen plus progestin menopausal hormone therapy safe with respect to endometrial cancer risk?
Int J Cancer
2013
;
132
:
417
26
.
44.
Brinton
LA
,
Felix
AS
,
McMeekin
DS
,
Creasman
WT
,
Sherman
ME
,
Mutch
D
, et al
Etiologic heterogeneity in endometrial cancer: evidence from a Gynecologic Oncology Group trial
.
Gynecol Oncol
2013
;
129
:
277
84
.
45.
Cuzick
J
,
Sestak
I
,
Bonanni
B
,
Costantino
JP
,
Cummings
S
,
DeCensi
A
, et al
Selective oestrogen receptor modulators in prevention of breast cancer: an updated meta-analysis of individual participant data
.
Lancet
2013
;
381
:
1827
34
.
46.
Yang
HP
,
Brinton
LA
,
Platz
EA
,
Lissowska
J
,
Lacey
JV
 Jr
,
Sherman
ME
, et al
Active and passive cigarette smoking and the risk of endometrial cancer in Poland
.
Eur J Cancer
2010
;
46
:
690
6
.
47.
Zhou
B
,
Yang
L
,
Sun
Q
,
Cong
R
,
Gu
H
,
Tang
N
, et al
Cigarette smoking and the risk of endometrial cancer: a meta-analysis
.
Am J Med
2008
;
121
:
501
8
e3
.
48.
Moore
SC
,
Gierach
GL
,
Schatzkin
A
,
Matthews
CE
. 
Physical activity, sedentary behaviours, and the prevention of endometrial cancer
.
Br J Cancer
2010
;
103
:
933
8
.
49.
Schmid
D
,
Behrens
G
,
Keimling
M
,
Jochem
C
,
Ricci
C
,
Leitzmann
M
. 
A systematic review and meta-analysis of physical activity and endometrial cancer risk
.
Eur J Epidemiol
2015
;
30
:
397
412
.
50.
Keum
N
,
Ju
W
,
Lee
DH
,
Ding
EL
,
Hsieh
CC
,
Goodman
JE
, et al
Leisure-time physical activity and endometrial cancer risk: dose-response meta-analysis of epidemiological studies
.
Int J Cancer
2014
;
135
:
682
94
.
51.
Biel
RK
,
Csizmadi
I
,
Cook
LS
,
Courneya
KS
,
Magliocco
AM
,
Friedenreich
CM
. 
Risk of endometrial cancer in relation to individual nutrients from diet and supplements
.
Public Health Nutr
2011
;
14
:
1948
60
.
52.
Bandera
EV
,
Kushi
LH
,
Moore
DF
,
Gifkins
DM
,
McCullough
ML
. 
Fruits and vegetables and endometrial cancer risk: a systematic literature review and meta-analysis
.
Nutr Cancer
2007
;
58
:
6
21
.
53.
Prentice
RL
,
Thomson
CA
,
Caan
B
,
Hubbell
FA
,
Anderson
GL
,
Beresford
SA
, et al
Low-fat dietary pattern and cancer incidence in the Women's Health Initiative Dietary Modification Randomized Controlled Trial
.
J Natl Cancer Inst
2007
;
99
:
1534
43
.
54.
Zhao
J
,
Lyu
C
,
Gao
J
,
Du
L
,
Shan
B
,
Zhang
H
, et al
Dietary fat intake and endometrial cancer risk: a dose response meta-analysis
.
Medicine (Baltimore)
2016
;
95
:
e4121
.
55.
Li
X
,
Zhao
J
,
Li
P
,
Gao
Y
. 
Dairy products intake and endometrial cancer risk: a meta-analysis of observational studies
.
Nutrients
2017
;
10
.
56.
Lafranconi
A
,
Micek
A
,
Galvano
F
,
Rossetti
S
,
Del Pup
L
,
Berretta
M
, et al
Coffee decreases the risk of endometrial cancer: a dose-response meta-analysis of prospective cohort studies
.
Nutrients
2017
;
9
.
57.
Zhou
Q
,
Li
H
,
Zhou
JG
,
Ma
Y
,
Wu
T
,
Ma
H
. 
Green tea, black tea consumption and risk of endometrial cancer: a systematic review and meta-analysis
.
Arch Gynecol Obstet
2016
;
293
:
143
55
.
58.
Zhou
Q
,
Guo
P
,
Li
H
,
Chen
XD
. 
Does alcohol consumption modify the risk of endometrial cancer? A dose-response meta-analysis of prospective studies
.
Arch Gynecol Obstet
2017
;
295
:
467
79
.
59.
Tang
YL
,
Zhu
LY
,
Li
Y
,
Yu
J
,
Wang
J
,
Zeng
XX
, et al
Metformin use is associated with reduced incidence and improved survival of endometrial cancer: a meta-analysis
.
BioMed Res Int
2017
;
2017
:
5905384
.
60.
Verdoodt
F
,
Friis
S
,
Dehlendorff
C
,
Albieri
V
,
Kjaer
SK
. 
Non-steroidal anti-inflammatory drug use and risk of endometrial cancer: a systematic review and meta-analysis of observational studies
.
Gynecol Oncol
2016
;
140
:
352
8
.
61.
Weiderpass
E
,
Pukkala
E
,
Vasama-Neuvonen
K
,
Kauppinen
T
,
Vainio
H
,
Paakkulainen
H
, et al
Occupational exposures and cancers of the endometrium and cervix uteri in Finland
.
Am J Ind Med
2001
;
39
:
572
80
.
62.
Wernli
KJ
,
Ray
RM
,
Gao
DL
,
Fitzgibbons
ED
,
Camp
JE
,
Astrakianakis
G
, et al
Occupational risk factors for endometrial cancer among textile workers in Shanghai, China
.
Am J Ind Med
2008
;
51
:
673
9
.
63.
Karageorgi
S
,
Gates
MA
,
Hankinson
SE
,
De Vivo
I
. 
Perineal use of talcum powder and endometrial cancer risk
.
Cancer Epidemiol Biomarkers Prev
2010
;
19
:
1269
75
.
64.
Neill
AS
,
Nagle
CM
,
Spurdle
AB
,
Webb
PM
. 
Use of talcum powder and endometrial cancer risk
.
Cancer Causes Control
2012
;
23
:
513
9
.
65.
Crawford
L
,
Reeves
KW
,
Luisi
N
,
Balasubramanian
R
,
Sturgeon
SR
. 
Perineal powder use and risk of endometrial cancer in postmenopausal women
.
Cancer Causes Control
2012
;
23
:
1673
80
.
66.
Fortuny
J
,
Sima
C
,
Bayuga
S
,
Wilcox
H
,
Pulick
K
,
Faulkner
S
, et al
Risk of endometrial cancer in relation to medical conditions and medication use
.
Cancer Epidemiol Biomarkers Prev
2009
;
18
:
1448
56
.
67.
Poole
EM
,
Lin
WT
,
Kvaskoff
M
,
De Vivo
I
,
Terry
KL
,
Missmer
SA
. 
Endometriosis and risk of ovarian and endometrial cancers in a large prospective cohort of U.S. nurses
.
Cancer Causes Control
2017
;
28
:
437
45
.
68.
Morimoto
LM
,
Newcomb
PA
,
Hampton
JM
,
Trentham-Dietz
A
. 
Cholecystectomy and endometrial cancer: a marker of long-term elevated estrogen exposure?
Int J Gynecol Cancer
2006
;
16
:
1348
53
.
69.
Lin
CF
,
Chan
HL
,
Hsieh
YH
,
Liang
HY
,
Chiu
WC
,
Huang
KY
, et al
Endometrial cancer and antidepressants: a nationwide population-based study
.
Medicine
2016
;
95
:
e4178
.
70.
Sperling
CD
,
Verdoodt
F
,
Friis
S
,
Dehlendorff
C
,
Kjaer
SK
. 
Statin use and risk of endometrial cancer: a nationwide registry-based case-control study
.
Acta Obstet Gynecol Scand
2017
;
96
:
144
9
.
71.
Ding
YY
,
Yao
P
,
Verma
S
,
Han
ZK
,
Hong
T
,
Zhu
YQ
, et al
Use of acetaminophen and risk of endometrial cancer: evidence from observational studies
.
Oncotarget
2017
;
8
:
34643
51
.
72.
Weiderpass
E
,
Adami
HO
,
Baron
JA
,
Wicklund-Glynn
A
,
Aune
M
,
Atuma
S
, et al
Organochlorines and endometrial cancer risk
.
Cancer Epidemiol Biomarkers Prev
2000
;
9
:
487
93
.
73.
Winer
I
,
Lehman
A
,
Wactawski-Wende
J
,
Robinson
R
,
Simon
M
,
Cote
M
. 
Tubal ligation and risk of endometrial cancer: findings from the Women's Health Initiative
.
Int J Gynecol Cancer
2016
;
26
:
464
71
.
74.
Abel
EL
,
Hendrix
SL
,
McNeeley
GS
,
O'Leary
ES
,
Mossavar-Rahmani
Y
,
Johnson
SR
, et al
Use of electric blankets and association with prevalence of endometrial cancer
.
Eur J Cancer Prev
2007
;
16
:
243
50
.
75.
Win
AK
,
Reece
JC
,
Ryan
S
. 
Family history and risk of endometrial cancer: a systematic review and meta-analysis
.
Obstet Gynecol
2015
;
125
:
89
98
.
76.
Johnatty
SE
,
Tan
YY
,
Buchanan
DD
,
Bowman
M
,
Walters
RJ
,
Obermair
A
, et al
Family history of cancer predicts endometrial cancer risk independently of Lynch Syndrome: Implications for genetic counselling
.
Gynecol Oncol
2017
;
147
:
381
7
.
77.
Dowty
JG
,
Win
AK
,
Buchanan
DD
,
Lindor
NM
,
Macrae
FA
,
Clendenning
M
, et al
Cancer risks for MLH1 and MSH2 mutation carriers
.
Hum Mutat
2013
;
34
:
490
7
.
78.
Bonadona
V
,
Bonaiti
B
,
Olschwang
S
,
Grandjouan
S
,
Huiart
L
,
Longy
M
, et al
Cancer risks associated with germline mutations in MLH1, MSH2, and MSH6 genes in Lynch syndrome
.
JAMA
2011
;
305
:
2304
10
.
79.
Ramsoekh
D
,
Wagner
A
,
van Leerdam
ME
,
Dooijes
D
,
Tops
CM
,
Steyerberg
EW
, et al
Cancer risk in MLH1, MSH2 and MSH6 mutation carriers; different risk profiles may influence clinical management
.
Hered Cancer Clin Pract
2009
;
7
:
17
.
80.
ten Broeke
SW
,
Brohet
RM
,
Tops
CM
,
van der Klift
HM
,
Velthuizen
ME
,
Bernstein
I
, et al
Lynch syndrome caused by germline PMS2 mutations: delineating the cancer risk
.
J Clin Oncol
2015
;
33
:
319
25
.
81.
Kempers
MJ
,
Kuiper
RP
,
Ockeloen
CW
,
Chappuis
PO
,
Hutter
P
,
Rahner
N
, et al
Risk of colorectal and endometrial cancers in EPCAM deletion-positive Lynch syndrome: a cohort study
.
Lancet Oncol
2011
;
12
:
49
55
.
82.
Sijmons
RH
,
Hofstra
RM
. 
Review: clinical aspects of hereditary DNA mismatch repair gene mutations
.
DNA Repair
2016
;
38
:
155
62
.
83.
O'Mara
TA
,
Glubb
DM
,
Amant
F
,
Annibali
D
,
Ashton
K
,
Attia
J
, et al
Identification of nine new susceptibility loci for endometrial cancer
.
Nat Comm
2018
;
9
:
3166
.
84.
Chen
MM
,
Crous-Bou
M
,
Setiawan
VW
,
Prescott
J
,
Olson
SH
,
Wentzensen
N
, et al
Exome-wide association study of endometrial cancer in a multiethnic population
.
PLoS One
2014
;
9
:
e97045
.
85.
Meyer
LA
,
Westin
SN
,
Lu
KH
,
Milam
MR
. 
Genetic polymorphisms and endometrial cancer risk
.
Expert Rev Anticancer Ther
2008
;
8
:
1159
67
.
86.
Spurdle
AB
,
Thompson
DJ
,
Ahmed
S
,
Ferguson
K
,
Healey
CS
,
O'Mara
T
, et al
Genome-wide association study identifies a common variant associated with risk of endometrial cancer
.
Nature genetics
2011
;
43
:
451
4
.
87.
Setiawan
VW
,
Yang
HP
,
Pike
MC
,
McCann
SE
,
Yu
H
,
Xiang
YB
, et al
Type I and II endometrial cancers: have they different risk factors?
J Clin Oncol
2013
;
31
:
2607
18
.
88.
Sherman
ME
,
Sturgeon
S
,
Brinton
LA
,
Potischman
N
,
Kurman
RJ
,
Berman
ML
, et al
Risk factors and hormone levels in patients with serous and endometrioid uterine carcinomas
.
Mod Pathol
1997
;
10
:
963
8
.
89.
Felix
AS
,
Weissfeld
JL
,
Stone
RA
,
Bowser
R
,
Chivukula
M
,
Edwards
RP
, et al
Factors associated with type I and type II endometrial cancer
.
Cancer Causes Control
2010
;
21
:
1851
6
.
90.
Yang
HP
,
Wentzensen
N
,
Trabert
B
,
Gierach
GL
,
Felix
AS
,
Gunter
MJ
, et al
Endometrial cancer risk factors by 2 main histologic subtypes: the NIH-AARP Diet and Health Study
.
Am J Epidemiol
2013
;
177
:
142
51
.
91.
Trabert
B
,
Wentzensen
N
,
Felix
AS
,
Yang
HP
,
Sherman
ME
,
Brinton
LA
. 
Metabolic syndrome and risk of endometrial cancer in the united states: a study in the SEER-medicare linked database
.
Cancer Epidemiol Biomarkers Prev
2015
;
24
:
261
7
.
92.
Cancer Genome Atlas Research N
,
Kandoth
C
,
Schultz
N
,
Cherniack
AD
,
Akbani
R
,
Liu
Y
, et al
Integrated genomic characterization of endometrial carcinoma
.
Nature
2013
;
497
:
67
73
.
93.
Allen
NE
,
Key
TJ
,
Dossus
L
,
Rinaldi
S
,
Cust
A
,
Lukanova
A
, et al
Endogenous sex hormones and endometrial cancer risk in women in the European Prospective Investigation into Cancer and Nutrition (EPIC)
.
Endocr Relat Cancer
2008
;
15
:
485
97
.
94.
Lukanova
A
,
Lundin
E
,
Micheli
A
,
Arslan
A
,
Ferrari
P
,
Rinaldi
S
, et al
Circulating levels of sex steroid hormones and risk of endometrial cancer in postmenopausal women
.
Int J Cancer
2004
;
108
:
425
32
.
95.
Zeleniuch-Jacquotte
A
,
Akhmedkhanov
A
,
Kato
I
,
Koenig
KL
,
Shore
RE
,
Kim
MY
, et al
Postmenopausal endogenous oestrogens and risk of endometrial cancer: results of a prospective study
.
Br J Cancer
2001
;
84
:
975
81
.
96.
Brinton
LA
,
Trabert
B
,
Anderson
GL
,
Falk
RT
,
Felix
AS
,
Fuhrman
BJ
, et al
Serum estrogens and estrogen metabolites and endometrial cancer risk among postmenopausal women
.
Cancer Epidemiol Biomarkers Prev
2016
;
25
:
1081
9
.
97.
Potischman
N
,
Hoover
RN
,
Brinton
LA
,
Siiteri
P
,
Dorgan
JF
,
Swanson
CA
, et al
Case-control study of endogenous steroid hormones and endometrial cancer
.
J Natl Cancer Inst
1996
;
88
:
1127
35
.
98.
Clendenen
TV
,
Hertzmark
K
,
Koenig
KL
,
Lundin
E
,
Rinaldi
S
,
Johnson
T
, et al
Premenopausal circulating androgens and risk of endometrial cancer: results of a prospective study
.
Horm Cancer
2016
;
7
:
178
87
.
99.
Hernandez
AV
,
Pasupuleti
V
,
Benites-Zapata
VA
,
Thota
P
,
Deshpande
A
,
Perez-Lopez
FR
. 
Insulin resistance and endometrial cancer risk: a systematic review and meta-analysis
.
Eur J Cancer
2015
;
51
:
2747
58
.
100.
Gunter
MJ
,
Hoover
DR
,
Yu
H
,
Wassertheil-Smoller
S
,
Manson
JE
,
Li
J
, et al
A prospective evaluation of insulin and insulin-like growth factor-I as risk factors for endometrial cancer
.
Cancer Epidemiol Biomarkers Prev
2008
;
17
:
921
9
.
101.
Zhan
Y
,
Wang
J
,
Ma
Y
,
Liu
Z
,
Xu
H
,
Lu
S
, et al
Serum insulin-like, growth factor binding protein-related protein 1 (IGFBP-rP1) and endometrial cancer risk in Chinese women
.
Int J Cancer
2013
;
132
:
411
6
.
102.
Trabert
B
,
Eldridge
RC
,
Pfeiffer
RM
,
Shiels
MS
,
Kemp
TJ
,
Guillemette
C
, et al
Pre-diagnostic circulating inflammation markers and endometrial cancer risk in the prostate, lung, colorectal and ovarian cancer (PLCO) screening trial
.
Int J Cancer
2017
;
140
:
600
10
.
103.
Gong
TT
,
Wu
QJ
,
Wang
YL
,
Ma
XX
. 
Circulating adiponectin, leptin and adiponectin-leptin ratio and endometrial cancer risk: evidence from a meta-analysis of epidemiologic studies
.
Int J Cancer
2015
;
137
:
1967
78
.
104.
Pfeiffer
RM
,
Park
Y
,
Kreimer
AR
,
Lacey
JV
 Jr
,
Pee
D
,
Greenlee
RT
, et al
Risk prediction for breast, endometrial, and ovarian cancer in white women aged 50 y or older: derivation and validation from population-based cohort studies
.
PLoS Med
2013
;
10
:
e1001492
.
105.
Husing
A
,
Dossus
L
,
Ferrari
P
,
Tjonneland
A
,
Hansen
L
,
Fagherazzi
G
, et al
An epidemiological model for prediction of endometrial cancer risk in Europe
.
Eur J Epidemiol
2016
;
31
:
51
60
.
106.
Fortner
RT
,
Husing
A
,
Kuhn
T
,
Konar
M
,
Overvad
K
,
Tjonneland
A
, et al
Endometrial cancer risk prediction including serum-based biomarkers: results from the EPIC cohort
.
Int J Cancer
2017
;
140
:
1317
23
.
107.
Sheikh
MA
,
Althouse
AD
,
Freese
KE
,
Soisson
S
,
Edwards
RP
,
Welburn
S
, et al
USA endometrial cancer projections to 2030: should we be concerned?
Future Oncol
2014
;
10
:
2561
8
.
108.
Menke
A
,
Casagrande
S
,
Geiss
L
,
Cowie
CC
. 
Prevalence of and trends in diabetes among adults in the United States, 1988–2012
.
JAMA
2015
;
314
:
1021
9
.
109.
Mozumdar
A
,
Liguori
G
. 
Persistent increase of prevalence of metabolic syndrome among U.S. adults: NHANES III to NHANES 1999–2006
.
Diabetes Care
2011
;
34
:
216
9
.
110.
Curtin
SC
,
Abma
JC
,
Ventura
SJ
,
Henshaw
SK
. 
Pregnancy rates for U.S. women continue to drop
.
NCHS Data Brief
2013
:
1
8
.
111.
Jamal
A
,
Agaku
I
,
O'Connor
E
,
King
B
,
Kenemer
J
,
Neff
L
. 
Current cigarette smoking among adults—United States, 2005–2013
.
MMWR Morb Mortal Wkly Rep
2014
;
63
:
1108
12
.
112.
Wright
JD
,
Herzog
TJ
,
Tsui
J
,
Ananth
CV
,
Lewin
SN
,
Lu
YS
, et al
Nationwide trends in the performance of inpatient hysterectomy in the United States
.
Obstet Gynecol
2013
;
122
(
2 Pt 1
):
233
41
.
113.
Jemal
A
,
Ward
EM
,
Johnson
CJ
,
Cronin
KA
,
Ma
J
,
Ryerson
B
, et al
Annual report to the nation on the status of cancer, 1975–2014, featuring survival
.
J Natl Cancer Inst
2017
;
109
.
114.
Anveden
A
,
Taube
M
,
Peltonen
M
,
Jacobson
P
,
Andersson-Assarsson
JC
,
Sjoholm
K
, et al
Long-term incidence of female-specific cancer after bariatric surgery or usual care in the Swedish Obese Subjects Study
.
Gynecol Oncol
2017
;
145
:
224
9
.
115.
Lu
KH
,
Loose
DS
,
Yates
MS
,
Nogueras-Gonzalez
GM
,
Munsell
MF
,
Chen
LM
, et al
Prospective multicenter randomized intermediate biomarker study of oral contraceptive versus depo-provera for prevention of endometrial cancer in women with Lynch syndrome
.
Cancer Prev Res
2013
;
6
:
774
81
.
116.
Jacobs
I
,
Gentry-Maharaj
A
,
Burnell
M
,
Manchanda
R
,
Singh
N
,
Sharma
A
, et al
Sensitivity of transvaginal ultrasound screening for endometrial cancer in postmenopausal women: a case-control study within the UKCTOCS cohort
.
Lancet Oncol
2011
;
12
:
38
48
.
117.
Sonoda
Y
,
Barakat
RR
. 
Screening and the prevention of gynecologic cancer: endometrial cancer
.
Best Pract Res Clin Obstet Gynaecol
2006
;
20
:
363
77
.
118.
Martinez-Garcia
E
,
Lopez-Gil
C
,
Campoy
I
,
Vallve
J
,
Coll
E
,
Cabrera
S
, et al
Advances in endometrial cancer protein biomarkers for use in the clinic
.
Expert Rev Proteomics
2018
;
15
:
81
99
.