Impact of Estrogen Exposure on Cancer Risk and Related Health Factors

1. Repro Cancers Review

2. Estrogen exposureacross the life course High estrogen exposure increases risk of breast, ovarian, and endometrial cancers Alcohol intake: increases conversion of testosterone to estrogen Breast Disease 24 (2005,2006) 17–35

3. Role of energy balance in cancer development Exp Diabetes Res. 2012;2012:789174

4. Other risk factors • HPV • Persistent infection necessary for cervical cancer to develop • Other risk factors are mainly things that are associated with increased sexual activity • PCOS • Anovulation prolonged estrogen secretion increased risk of endometrial cancer • Evidence for breast and ovarian cancer is shaky • BRCA1 & BRCA2 mutations • Genes code for tumor suppressor genes • Mutations increase risk of breast and ovarian cancer

5. GI Review

6. Mouth & pharynx • Dental illness problems chewing • Certain illness and medication problems salivating • Exs: Sjorgren’s syndrome: autoimmune attack of salivary glands; anti-diarrheal drugs • Problems swallowing • Exs: ALS, spinal cord injury, stroke

7. Esophagus • Gastroesophageal reflux disease (GERD) • Risk factors: babies, pregnancy, obesity, lying down, smoking, certain foods, lupus • Consequences: heartburn; Barrett’s esophagus; dental cavities • Hiatal hernia • Can cause GERD • Barrett’s Esophagus • Caused by GERD • Consequences: esophageal cancer

8. Stomach • Peptic ulcers • risk factors weaken mucosal layer: H. pylori infection, NSAIDS (inhibit prostaglandins), hypersecretion of acid

9. Intestines | 1 • Irritable bowel syndrome (IBS): cramping, diarrhea and/or constipation, passing of mucous stools • Cause unknown • Irritable bowel disease (IBD): more severe • Exs: Crohn’s disease, ulcerative colitis • Treated with corticosteroids

10. Intestines | 2 • Vomiting: controlled by vomiting center in medulla; protects against ingesting toxins • Consequences of severe vomiting: • dehydration (↓blood volume ↓ blood pressure) • metabolic alkalosis (lose high amounts of HCl (acid) blood becomes alkaline) • hypokalemia (↓blood volume ↑ aldosterone release retain Na+ and water excrete K+) • Malnutrition (excess loss of calories)

11. Intestines | 3 • Diarrhea: leading cause of death worldwide in children • consequences of extreme diarrhea • dehydration (↓blood volume ↓ blood pressure) • metabolic acidosis (lose high amounts of KHCO3 (base) blood becomes acidic) • hypokalemia (↓blood volume ↑ aldosterone release retain Na+ and water excrete K+)

12. Intestines | 4 • Osmotic diarrhea: retention of unabsorbable substances in intestines--> water follows • Ex: lactose intolerance • Secretory diarrhea: excessive intestinal mucosal secretion of large volume of fluid & electrolytes • Ex: cholera

13. Intestines | 5 • Diarrhea due to malabsorption: presence of unabsorbed material in gut; can cause water loss by osmosis and other factors • Ex: celiac disease • Loss of intestinal villi (decreased absorptive surface) • Loss of intestinal enzymes and hormones • Inflammation • Hemorrhagic diarrhea: caused by infectious agent, results in bloody stool • Ex: certain E. coli strains • Diarrhea due to altered motility: fast transit • Ex: dumping syndrome after gastric bypass surgery

14. Pancreas | 1 • Acute pancreatitis: acute inflammation and destructive autodigestion of pancreas • Causes: alcohol abuse; gallstones • Consequences: pain, nausea, vomiting, fever, shock (low blood pressure), increased serum amylase and lipase, jaundice, acidosis, hyperkalemia

15. Pancreas | 2 • Chronic pancreatitis: chronic inflammation resulting in fibrosis, calcification, and loss of exocrine function • Causes: mainly alcoholism • Consequences: pancreatic insufficiency (fat in stool & diarrhea); supplementation with insulin and pancreatic enzymes • Pancreatic cancer: highly fatal

16. Liver | 1 • Cirrhosis: gradual degeneration of liver cells, replaced with scar tissue • Causes: mainly alcoholism • Consequences: • portal hypertension (fibrosis causes backup of blood in hepatic portal vein) • ascites (accumulation of watery fluid in peritoneal cavity due to portal hypertension and increased vascular permeability from inflammation) • Infection (blood from intestine liver may be infected) • Edema (reduced albumin production fluid build up in tissues) • Neurological disorders (build up of ammonia)

17. Liver | 2 • Consequences continued: • Increased bleeding (reduced clotting factors and vit K) • Endocrine disorders (reduced binding proteins for fat-soluble hormones) • Jaundice, diarrhea, fatty stool • Problems with glucose metabolism (hypoglycemia from lack of gluconeogenesis; hyperglycemia from bypass of hepatic portal system) • Problems with lipid metabolism • Increased serum aminotransferase and alkaline phosphatase • Problems with salt and water balance

18. questions

19. Celiac disease can result in • Anemia • Osteoporosis • Short stature (if acquired in childhood) • Miscarriage • All of the above

20. When the lower esophageal sphincter is pushed into the thoracic cavity, it is known as • Barrett’s esophagus • Heartburn • Hiatal hernia • Peptic ulcer

21. Irritable Bowel Disease (IBD) is typically treated with which drug to reduce inflammation? • Corticosteroids • Vitamin B12 supplementation • Antibiotics • Antacids

22. Excessive vomiting can ______ blood pH and excessive diarrhea can _______ blood pH. • Lower, lower • Lower, raise • Raise, lower • Raise, raise (low pH=more acidic; high pH=more alkaline)

23. Excessive vomiting can ______ blood potassium levels and excessive diarrhea can _______ blood potassium levels. • Lower, lower • Lower, raise • Raise, lower • Raise, raise

24. Angiogenesis refers to • Limitless potential to replicate • Ability to form new blood vessels • Ability of a tumor to metastasize • Increased cellular proliferation

25. Which of the following statements is true? • Oncogenes are never expressed in normal cells • Functional tumor suppressor genes increase the likelihood of cancer development • Overexpression of an oncogene can contribute to cancer development • HER2 is an example of a tumor suppressor gene

26. In the US, incidence rates of these cancers are higher in Caucasians vs. African Americans (choose all that apply) • Testicular cancer • Prostate cancer • Breast cancer • Endometrial cancer