Women and Cancer

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• Women and Cancer

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Causes

• cancer cells arise due to progressive mutations
  of DNA
• causes
• inherited mutations
• viruses, chemicals, radiation
• mutations involve 2 types of genes
• proto-oncogenes dormant forms of cancer-causing
  genes
• tumor-suppressor genes required for
  differentiation into mature cell types

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Cancerous vs. Normal Cells

• Specialized with specific form and function
• Enter the cell cycle about 50x, then die
• Normal nuclei with 46 chromosomes
• Adhere to neighbor cells exhibit contact
  inhibition
• Require growth factors for survival

• Not specialized dont contribute to normal
  functioning of body part
• Enter cycle repeatedly are immortal
• Abnormal nuclei with deletions / amplif. of
  genes abnormal chrom.
• No restraint will pile on top of one another
• Reduced need for growth factors

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Known carcinogens

• 90 of cancers are environmentally induced
• avoid these factors reduce your risk
• Known carcinogens Target tissue
• high energy radiation tissue exposed
• UV radiation skin
• hormones breast, endometrium, ovary,
  prostate
• fat colon, breast, prostate
• nitrites stomach, esophagus
• smoking lungs, many others
• xenoestrogens? reproductive tissues?

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Breast cancer

• 50,000 US women die per year from breast cancer
• 5-10 due to inherited mutations
• risk increases with age
• ages 20-30, 1 in 2500 chance of developing b.c.
• ages 30-40, 1 in 63
• ages 40-60, 1 in 28
• by age 85, 1 in 9
• by age 100, 1 in 8
• breast cancer incidence is increasing
• overall risk in America has increased from 1 in
  11 in 1980s to 1 in 9 in late 1990s
• not a gender-specific disease!
• 1400 cases of male breast cancer reported / year

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Inherited breast cancer

• 5-10 of cases due to inherited mutation
• risk is 2x greater than general population if
  mother or sister developed disease
• two genes implicated in breast cancer
• BRCA1 gene (chromosome 17) encodes tumor
  suppressor
• protects against breast and ovarian cancer
• BRCA2 gene (chromosome 13) encodes tumor
  suppressor
• protects against breast cancer in both sexes
• Inherit abnormal BRCA gene 80 chance of
  developing breast cancer

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BRCA genes

• mutated BRCA genes can be inherited from mother
  or father
• normal BRCA genes can be mutated by environmental
  factors
• BRCA mutations probably account for 38 of all
  cases
• removal of both breasts lowers the risk of
  getting the disease by 91 percent!

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Noninherited breast cancer

• includes 90 of cases
• factors that appear to influence risk
• sum of lifetime exposure to estrogens (depends on
  age of menarche, menopause, pregnancies,
  lactation possibly xenoestrogens? birthweight?)
• obesity
• diet (vitamin A, I3C, low fat)
• exercise!
• others - smoking, place of residence

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Other breast cancer genes

• breast cancer metastasis suppressor-1 (BRMS1)
• located on chromosome 11
• appears to be the first suppressor of metastasis
  identified for breast cancer
• BRMS1 was expressed less as a cell's malignancy
  increased
• researchers then introduced chromosome 11 into a
  metastatic breast cell line
• While the cells still had the ability to form
  tumors, their ability to metastasize was greatly
  reduced
• between half and two-thirds of patients with
  late-stage breast cancer lose copies of
  chromosome 11

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CHEK 2

• CHEK2 may account for 1 of all breast cancers in
  women, and 9 of those in men
• gene is thought to be involved in repairing
  damaged DNA
• a mutation in it doubles a woman's risk of
  developing breast cancer (10-fold increase for
  men)

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HER2

• Human epidermal growth factor receptor type 2
• Proto-oncogene https//www.her2status.com/public/p
  ublic_home.htm
• of copies amplified in some cases of breast
  cancer
• 30 of breast cancer patients have excess HER2
  more aggressive cancer
• Drug Herceptin blocks actions of HER2 slows
  metastasis

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Cervical Cancer

• incidence decreases after menopause
• annual cervical (pap) smears can detect
• in older women, not a fast spreading cancer
  (opposite is true in young women with human
  papilloma virus)
• prognosis good (5 yr. survival 100)
• risk factors
• greater number of sexual partners
• venereal diseases
• smoking

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HPV

• causes venereal warts -moist, soft,
  cauliflower-like bumps (within 3 weeks - 8
  months)
• appear on cervix, labia, vulva, perineum in
  females
• treated topically with dry ice, liquid nitrogen
  warts dry up and fall off in a few days
• sometimes surgery is necessary to remove
• warts may recur
• major cause of cervical cancer (95 of cases
  associated with HPV)
• also associated with cancer of the penis, vagina,
  anus

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Endometrial Cancer

• 80 of cases occur after menopause
• increased risk associated with obesity, diabetes,
  hypertension, infertility
• most common symptom vaginal bleeding
• sometimes discovered due to uterine enlargement
• rarely detected by pap smear
• pelvic exam required for diagnosis
• typically slow to metastasize
• treatment hysterectomy possible chemotherapy
• 5 yr survival rate 85

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Ovarian Cancer

• can occur anytime after puberty, but most often
  after menopause
• Previously difficult to detect no symptoms
  until advanced stages
• before detection, often spreads to ovarian,
  uterine, peritoneal cavity
• new diagnostic measure test for levels of
  lysophosphatidic acid (LPA)
• risk factors BRAC 1 gene smoking
• combination pills, bearing children seems to
  lower risk
• Previous blood test CA-125

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Smoking

• THE major cause of cancer
• Quitting smoking reduces risk more than all other
  methods combined
• Lung cancer is most common cancer in women
• Female smokers 2x more likely to get lung cancer
  (smaller lungs)
• Women may be more genetically vulnerable to
  tobacco smoke
• Smokers at increased risk for all gynecologic
  cancers
• Nonsmoking women with husbands who smoke have
  higher cancer rates

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Prevention

• Increase consumption of plant foods
• Decrease consumption of fats
• Exercise!
• Minimize time in sun
• Reduce alcohol consumption

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Endometrial cancer

• rarely detected by pap smear
• pelvic exam required for diagnosis
• typically slow to metastasize
• treatment hysterectomy possible chemotherapy
• 5 yr survival rate 85

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Endometrial cancer

• rarely detected by pap smear
• pelvic exam required for diagnosis
• typically slow to metastasize
• treatment hysterectomy possible chemotherapy
• 5 yr survival rate 85

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Ovarian Cancer

• can occur anytime after puberty, but most often
  after menopause
• Previously difficult to detect no symptoms
  until advanced stages
• before detection, often spreads to ovarian,
  uterine, peritoneal cavity

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Ovarian cancer

• risk factors BRAC 1 gene smoking
• combination pills, bearing children seems to
  lower risk
• blood test CA-125
• new diagnostic measure test for levels of
  lysophosphatidic acid (LPA)

22
Smoking

• THE major cause of cancer
• Quitting smoking reduces risk more than all other
  methods combined
• Lung cancer is most common cancer in women
• Female smokers 2x more likely to get lung cancer
  (smaller lungs)

23
Smoking

• Women may be more genetically vulnerable to
  tobacco smoke
• Smokers at increased risk for all gynecologic
  cancers
• Nonsmoking women with husbands who smoke have
  higher cancer rates