*2015.03.22 ( 일 ) 대한비만학회 제 30 차 춘계연수강좌 tying obesity and cancer...
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*2015.03.22 ( 일 ) 대한비만학회 제 30 차 춘계연수강좌
Tying Obesity and Cancer
인제대학교 의과대학 가정의학교실 김 종 우
• 비만하면 암에 잘 걸리나 ?
• 살을 빼면 암에 덜 걸리나 ?
• 비만하면 암 치료가 잘 안되나 ?
• ‘ 가설수준’ 에서의 대표적인 기전은 ?
Objectives
Obesity
Obesity
Obesity
Impact of Obesity on Cancer
Impact of Obesity on Cancer
Impact of Obesity on Cancer
Impact of Obesity on Cancer
WCRF & AICR
WCRF & AICR
“ Obesity is an established risk factor
for several cancers.”
WCRF & AICR, 2007
Prevalence of Obesity
OECD Report, September 2010
Recent Prevalence of Obesity and Cancer
Recent Prevalence of Obesity and Cancer
Recent Prevalence of Obesity and Cancer
Recent Prevalence of Obesity and Cancer
Initial BMI and Risk for Breast Cancer
Wt. Reduction after Breast Cancer Dx.
Wt. Reduction after Breast Cancer Dx.
Impact of Weight Reduction on Cancer
Impact of Weight Reduction on Cancer
Impact of Weight Reduction on Cancer
SOS study
Impact of Weight Reduction on Cancer
Impact of Weight Reduction on Cancer
Possible Mechanisms
Possible Mechanisms
Fat Tissue as an Endocrine Organ in Carcinogenesis
Front Physiol. 2013; 4: 275.
Fat Tissue as an Endocrine Organ in Carcinogenesis
Front Physiol. 2013; 4: 275.
Possible Mechanisms
• Insulin-IFG-1 axis
• Sex Hormones
• Adipokines
Possible Mechanisms
IR & IGF-1
High Insulin Levels as an Adverse Px. Factor
1. Breast
2. Colorectum
3. Prostate
High Insulin Levels as an Adverse Px. Factor
High Insulin Levels as an Adverse Px. Factor
“ ↑ CRC incidence with C-peptide levels
in the highest vs. lowest quartile ”
High Insulin Levels as an Adverse Px. Factor
Sex Hormones in Obesity
Sex Hormones in Obesity
• Higher rates of conversion of androgenic precursors to estradiol
• Increased aromatase activity through adipose tissue
• Data indicates that estrogen is both mitogenic and mutagenic
Leptin
• Leptin stimulates colorectal, esophageal, breast and prostate cancer cells in vitro.
• Long arm of leptin receptor (LRb) activates,– PI3 kinase
– MAPK
– STAT (signal transduce and activator transcription)
– C-fos
Leptin
• Leptin is a proangiogenic factor.
(↑ expression of MMP-2, 9)
• Leptin promotes aromatase expression in breast tissue.
Adiponectin
Adiponectin
• Most abundant adipokine
• Important insulin sensitizing agent
• Inverse association of adiponecitn concentrations and cancer
• Antiproliferative effects– ERK
– ERK1
– MAPK kinases
– Induces p53 and Bax
Another Problems in Obese Cancer Patients
• Tumor progression ↑
• Tumor recurrences ↑
Obstacles in Obese Cancer Patients
• Dosing Problems– Too toxic?
– Lesser dosing?
• Technical Problems– Surgery
– Radiotherapy
Conclusion
Conclusion
Conclusion
Conclusion