Obesity increases the risk of several gynecological cancers. It is a major risk factor for endometrial cancer, increasing risk by 2.6-5.8 times depending on the degree of obesity. Postmenopausal obesity also increases breast cancer risk by fueling estrogen production, and is associated with 10% of postmenopausal breast cancer cases. Evidence also links obesity to a modest increase in ovarian cancer, especially premenopausally and for certain histologic subtypes. Globally, obesity is the third leading cause of cancer and is associated with around 500,000 new cancer cases annually, making it an important preventable risk factor.

1. OBESITY
&
GYNECOLOGICAL CANCER
Prof. Aboubakr Elnashar
Benha university Hospital, EgyptABOUBAKR ELNASHAR

2. CONTENTS
 INTRODUCTION
1.ENDOMETRIAL CANCER
2.BREAST CANCER
3.OVARIAN CANCER
4. CERVICAL CANCER
5.OBESITY AS AN AVOIDABLE CAUSE OF CANCER
ABOUBAKR ELNASHAR

3.  Prevalence of Obesity
https://www.google.com.eg/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&cad=rja&uact=8&ved=0ahUKEwje_93djLvSAhVHRhQKHUJSCfQQjRwIBw&url=https%3A%2F%2Fscconner.wordpress.com%2F2012%2F05%2F09%2Fegypt-independent-
urbanization-marriage-poverty-and-shame-the-many-faces-of-obesity-in-egyptian-women-by-nadine-ibrahim%2F&bvm=bv.148747831,d.ZGg&psig=AFQjCNGvknhsipEWVJ-uiCNVib5Ff7nZXg&ust=1488656052705848
ABOUBAKR ELNASHAR

4. Incidence of Gynecologic Cancers in Egypt
0
5
10
15
20
25
Breast
Cancer
Cervical
Cancer
Ovarian
Cancer
Uterine
Cancer
Percent
Source: GLOBOCAN 2000.
ABOUBAKR ELNASHAR

5. ABOUBAKR ELNASHAR

6.  Convincing
1. Endometrial cancer
2. Postmenopausal breast
cancer
3. Colorectal cancer
4. Renal cell carcinoma
5. Esophageal
adenocarcinoma
6. Pancreatic cancer
7. Liver cancer
 Probable
1. Ovarian cancer
2. Gallbladder
cancer
3. Gastric cardia
cancer
World Cancer Research Fund, 2016
ABOUBAKR ELNASHAR

7. Major hormonal pathways
linking obesity with risk of
cancer
ABOUBAKR ELNASHAR

8.  Promotion of cancer in obese patients.
1. Endogenous sex hormones
2. Insulin resistance/hyperinsulinaemia,
3. Adipokines, cytokines
4. Chronic inflammation
(Benedetto et al, 2015)
ABOUBAKR ELNASHAR

9. 1. ENDOMETRIAL CANCER
 The 6th most common cancer in women worldwide
 The most common gynecologic malignancy in the developed
world.
ABOUBAKR ELNASHAR

10.  Obesity
 Significantly increases the incidence of endometrial
cancer
(Modesitt , van Nagell , 2005)
 Mild obesity
2.6-fold increase
 Moderate obesity
4.7-fold increase
 Central obesity
Twofold increase
 Early-life obesity
 moderately increased risk of endometrial cancer
later in life.
ABOUBAKR ELNASHAR

11. OR of endometrial cancer in obese women
0.4
0.8 0.7
2.1
4.1
20-25 25-29.9 30-34.9 35-39.9 >40
BMI, kgm2
×1.9
×5.8
E. Ilenko, N. Artymuk, 2007
ABOUBAKR ELNASHAR

12. Endometrial Caner in Egypt
0
5
10
15
20
25
30
35
Overall ≥75 Years ≥60-74 Years ≥50-59 Years
Incidence/100,000 Women
Ibrahim AS et al. 2014
ABOUBAKR ELNASHAR

13.  Mechanisms
1. prolonged exposure to unopposed estrogen and
hyperandrogenism
2. insulin resistance
3. chronic inflammation
4. adipokines.
ABOUBAKR ELNASHAR

14. Hypothesized biologic pathways relating excess obesity to endometrial cancer risk.
ABOUBAKR ELNASHAR

15.  Obesity
twofold increase in endometrial cancer-specific
mortality.
ABOUBAKR ELNASHAR

16. 2. BREAST CANCER
 The most common cancer among women
 25.2 % of incident female cancer cases
ABOUBAKR ELNASHAR

17.  Obesity
 relationship and breast cancer risk is complex
 differs by
1. tumor characteristics
2. menopausal status
3. exogenous hormone use.
ABOUBAKR ELNASHAR

18.  Obesity
 has opposing effects on breast cancer risk,
depending on the window of exposure
 Premenopausal women, obesity, in childhood or
during adult life:
 decreased risk of both hormone receptor-
positive and hormone receptor-negative
disease.
 {reduced exposure to endogenous
progesterone because of
obesity-induced ovarian hyperandrogenism}
(Benedetto et al, 2015)
ABOUBAKR ELNASHAR

19.  Postmenopausal
 increases risk of
 hormone receptor-positive disease
{oestrogen receptor (ER)-progesterone receptor (PR)-positive}
 limited to women not using HRT
 support the hypothesis that estrogens may be
the crucial link
 After menopause
 adipose tissue is the major source of estrogens
 obesity is associated with higher estrogen
concentrations, which
 have tumor-promoting activities.
 may explain the higher breast cancer risk.
ABOUBAKR ELNASHAR

20.  Weight gain in postmenopausal
 increases risk of postmenopausal disease
 limited to
 women not using HRT
 hormone receptor-positive disease.
ABOUBAKR ELNASHAR

21. Mechanisms linking adiposity and breast cancer
{insulin resistance: increased levels of circulating
insulin: reduced hepatic synthesis of SHBG
increased peripheral aromatisation of
androgens: increased levels of estrogens
(Key et al, 2003)}ABOUBAKR ELNASHAR

22.  Obesity
 10 % of all postmenopausal breast cancer cases
worldwide
 14 % of cases in North America and Europe, can
be attributed to obesity
[Arnold et al, 2015].
 highlight the relevance of
 maintaining a healthy weight
 minimizing weight gain, as a strategy for
modulating breast cancer risk.
ABOUBAKR ELNASHAR

23.  Obesity
 poorer breast cancer-specific survival
 irrespective of
 menopausal status or
 hormone receptor status of the tumor.
ABOUBAKR ELNASHAR

24. 3. OVARIAN CANCER
 The 7th most common cancer among women
 Incidence rates
 highest in developed regions
 lower in less developed regions
ABOUBAKR ELNASHAR

25.  Data are less convincing
 43 studies
 3,491,943 participants
limited, inconsistent evidence of a positive
association between obesity and ovarian cancer
risk.
(Foong, Bolton;2017, SR)
ABOUBAKR ELNASHAR

26.  Obesity:
 Modestly increase of premenopausal ovarian
cancer which are less likely to be of high-grade serous histology
(Modesitt , van Nagell , 2005)
 Each 5-unit higher BMI: 7 % higher risk of ovarian
cancer
[Clendenen et al, 2011].
 Risk of certain histologic subtypes
 low-grade serous
 invasive mucinous tumors.
ABOUBAKR ELNASHAR

27.  Obesity
 not a strong risk factor for ovarian cancer,
particularly compared to reproductive and
hormonal factors
 {1. ovarian cancer is a heterogeneous disease
2. association with obesity may differ according to
type of tumor}
[Clendenen et al, 2011].
ABOUBAKR ELNASHAR

28.  Mechanisms
1. inflammatory pathways
2. hormonal factors, including androgens.
ABOUBAKR ELNASHAR

29. 4. CERVICAL CANCER
 data are less convincing
 A modest positive association between BMI and
cervical cancer
 {impact on glandular cancers or decreased screening
compliance}.
ABOUBAKR ELNASHAR

30. OBESITY AS AN AVOIDABLE CAUSE OF CANCER
(Attributable Risks)
 Endometrial, post-menopausal breast, and colon
cancers
 2/3 of cancers attributable to obesity.
 Obesity
 an established risk factor for increased incidence
of several adult cancers.
 Worldwide
 3rd commonest attributable risk factor for
cancer (after smoking and infection)
 Western populations
 2nd biggest preventable cause of cancer after
smoking.
ABOUBAKR ELNASHAR

31.  Population Attributable Fraction: PAF
 Excess cancers attributable to obesity in populations
 Avoidable cases and the opportunity for
prevention.
 Worldwide attributed to obesity
 3.6 % or
 half a million new cancer cases in adults
 Higher in women compared with men
(5.4 % vs. 1.9 %).
ABOUBAKR ELNASHAR

32. Estimated numbers and PAFs of cancer cases
associated with high BMI
(Andrew et al, 2016)
ABOUBAKR ELNASHAR

33. Estimated PAFs by major risk factors for cancer at a
global level and for the UK
(Andrew et al, 2016)
ABOUBAKR ELNASHAR

34. You can get this lecture and 424
lecture from:
1.My scientific page on Face book:
Aboubakr Elnashar Lectures.
https://www.facebook.com/groups/2277
44884091351/
2.Slide share web site
3. elnashar53@hotmail.com
4.My clinic: Althwara st, Mansura, Egypt
ABOUBAKR ELNASHAR