Adipocytokines and Their Relationship to Obesity and Endometrial Cancer
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 100
- 试验地点
- 1
- 主要终点
- Correlation Between Circulating Levels of These Markers and Demographic Characteristics.
研究概览
简要总结
The number of women diagnosed with uterine cancer continues to rise each year. Since the early 1990s, there has been almost 55% rise in the United Kingdom (UK). 34% of endometrial cancer can be attributed to obesity. In the obese state, the function of adipose tissue deteriorates resulting in a state of chronic inflammation. Adipocytokine-related signalling pathways promote cancer development by causing inflammation, cell proliferation, DNA damage and by inhibiting apoptosis. The investigators postulate that adipocytokines levels are significantly different in uterine cancer patients of different weight categories and different grade/stage/ type of tumour.
Any woman attending the hospital with endometrial cancer and receiving treatment here will be invited to participate in the study. Consent will be sought to obtain 30mls (2 1/2 tablespoons) of venous blood at the time of surgery, on day 1 post-surgery and 3/6 months post-surgery during routine follow-up to check biomarker (adiponectin, leptin, tumour necrosis factor alpha, interleukin-6, Insulin-like growth factors 1 and 2) levels to see if the markers can be used to assess response to treatment. The investigators will also get consent to collect tissue - adipose tissue (after surgery) and uterine cancer tissue and lymph nodes (after histo-pathological evaluation) to assess for biomarkers. The investigators will also obtain blood samples from patients undergoing chemotherapy for advanced stage endometrial. All tissues procured will be anonymised and analysed at the oncology laboratory, Leggett building, University of Surrey and later correlated with patients' medical data as well as with tumour grade, stage and type. The investigators will also use archival tissue blocks stored at the same laboratory for analysis (previously consented for use in research). These are anonymised tissue and there is no link to patients' data.
The aim would be to ultimately find immuno-stimulatory/ suppressive biomarkers in order to develop novel diagnostic/ prognostic tools.
详细描述
- BACKGROUND
Endometrial cancer is the most common malignancy of the female genital tract. It is the fourth most common cancer in the UK with around 9,500 new cases in 2017, current lifetime risk being 1 in 36 women. The number of women diagnosed with endometrial cancer continues to rise each year. Since the early 1990s, uterine cancer incidence rates have increased by almost three-fifths (55%) in the UK (2015-2017). The association between endometrial cancer and obesity is well documented. 7.5% of all cancers in women in UK are attributable to being overweight / obese (BMI ≥25 kg/m2). For endometrial cancer, this risk rises to 34%. A review of meta-analyses showed endometrial cancer risk is 16% higher per 5 kg- gained during adulthood, 29% higher per 10cm increase in hip circumference and 27% higher per 10cm increase in waist circumference. This higher endometrial cancer risk with raised BMI is present in both pre- and post-menopausal women. Moreover, patients who are obese tend to have a poorer outcome with more co-morbidities than their non-obese counterparts.
In the overweight and obese state, the function of the adipose tissue deteriorates resulting in a state of chronic inflammation. In this inflammatory state, adipocytes and macrophages secrete several molecules, adipokines and inflammatory cytokines, which may promote tumour development and angiogenesis and stimulate adhesions and migration of cells.
Most implicated adipocytokines in the tumorigenesis pathway are adiponectin, leptin, tumour necrosis factor-α (TNF-α), Interleukin-6 (IL-6) and Insulin-like growth factor 1 and 2 (IGF 1 and 2).
Adipocytokine related signalling pathways are important in the development of an inflammatory microenvironment for tumours. This process is thought to increase the risk of endometrial cancer by inducing cell proliferation and preventing cell apoptosis. Adiponectin, the most abundant adipokine, has been suggested to have anti-angiogenic, anti-inflammatory, and anti-apoptotic properties. Raised leptin levels in obese state promotes inflammation by stimulating the production of IL-6, TNFα as well as IL-1 and IL-126. Leptin and adiponectin secretion are counter-regulated in vivo. A study by Luhn et. al. has shown adiponectin to have inverse relationship with the risk of endometrial cancer and leptin to have a direct correlation.
研究设计
- 研究类型
- Observational
- 观察模型
- Case Control
- 时间视角
- Prospective
入排标准
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Women diagnosed with endometrial cancer
- •Age 18 or above
- •Of sound mind so they can give informed consent
- •Historical tissue sample/ blocks from previous cases in the laboratory in the University of Surrey, also be used if appropriate consent is in place.
排除标准
- •Under 18yrs age
- •Unable to give consent /denies consent
结局指标
主要结局
Correlation Between Circulating Levels of These Markers and Demographic Characteristics.
时间窗: Data collected at baseline
Correlation between circulating levels of these markers and demographic characteristics such as age, parity, smoking status, menopausal status, medication use, use of HRT or hormonal contraception, the prevalence of diabetes and hypertension, any prior significant medical history or history of cancer and family history of cancer.
Correlation Between Circulating Levels of These Markers (Day 0) and Cancer Characteristics in the Study Population, Using Linear Regresion.
时间窗: Data collected at baseline (day 0)
Data on endometrial cancer histological characteristics, including grade, stage, histology, LVSI, MELF and MSI were collected from histology reports. Endometrial cancer grade is based on glandular organisation: Grade 1 (\<5% non-glandular), Grade 2 (6-50%), and Grade 3 (\>50% non-glandular). Staging reflects cancer spread, from localised to distant involvement. Type 1 (70-80%) is estrogen-related cancer usually endometrioid histology, while Type 2 (10-20%) arises from atrophic endometrium, of non-endometrioid histology. A lower grade and stage and type 1 histology is associated with better prognosis. LVSI, cancer in lymphatic/vascular spaces of the myometrium, is an independent risk factor for recurrence. MELF (microcystic, elongated, fragmented myometrial invasion) correlates with larger tumours, deeper invasion, and LVSI. MSI indicates DNA mismatch repair defects and is linked to advanced histological features, such as deep invasion and high-grade endometrial cancers.
The Difference in Circulating Plasma Levels of Adiponectin Between Study and Control Patients
时间窗: The levels of the markers between the two groups of patients were compared at baseline (day 0) and presented here.
Plasma levels of adiponectin will be measured by ELISA in both the study and the control populations, and the results compared using linear regression tests.
The Difference in Circulating Plasma Levels of Leptin, IGF1 and IGF2 Between Study and Control Patients.
时间窗: The levels of the markers between the two groups of patients were compared at baseline (day 0) and presented here.
Plasma levels of leptin, IGF1 and IGF2 will be measured by ELISA in both the study and the control populations, and the results compared using linear regression tests.
The Difference in Circulating Plasma Levels of IL6 and TNFα Between Study and Control Patients.
时间窗: The levels of the markers between the two groups of patients were compared at baseline (day 0) and presented here.
Plasma levels of IL6 and TNFα will be measured by ELISA in both the study and the control populations, and the results compared using linear regression tests.
Correlation Between the Markers and Study Patients' Obesity Status
时间窗: Levels of the markers were compared with BMI of the study patients at baseline i.e. Day 0
Correlation between the markers and patients' obesity status using WHO BMI subgroups.
Correlation Between the Markers and Control Patients' Obesity Status
时间窗: BMI was measured at baseline only for the control population.
Correlation between the markers and patients' obesity status using WHO BMI subgroups.
次要结局
- Correlation Between Circulating IL6 and TNF Levels and Their Expression in Endometrial Tissue.(At baseline, one time point measurement, Day 0)
- Correlation Between Circulating Leptin, IGF1 and IGF2 Levels and Their Expression in Endometrial Tissue.(At baseline, one time point measurement, Day 0)
- Changes in Adiponectin Levels Before (Day 0) and After Surgery in the Study Population (at 6 Months).(6 months)
- Changes in Leptin, IGF1 and IGF2 Levels Before (Day 0) and After Surgery in the Study Population (at 6 Months).(6 months)
- Changes in IL6 and TNFα Levels Before (Day 0) and After Surgery in the Study Population (at 6 Months).(6 months)
- Expression of These Biomarkers and Their Receptors in Endometrial Cancer Tissue and Adipose Tissue(The expression of these markers were investigated in the two tissue samples at baseline only (day 0).)
- Expression of These Biomarkers and Their Receptors in Endometrial Cancer Tissue and Lymph Nodal Tissue(The expression of these markers were investigated in the two tissue samples at baseline only (day 0).)
- Correlation Between Circulating Adiponectin Levels and Their Expression in Endometrial Tissue.(At baseline, one time point measurement, Day 0)