14. specific cancers

prostate or breast

lung and bronchus

colorectal

#1 cause of death in Canada

1 in 2 Canadians will develop cancer in their lifetime

1 in 4 Canadians will die from cancer

thyroid (98% 5 year survival rate)

testes

prostate

breast

melanoma

pancreas (8% 5 year survival rate)

esophagus

lungs + bronchus

liver

brain

we live longer

better diagnostic methods are better

heart disease rates are dropping (they live long enough to get cancer)

12.5%

ethnicity: black > white until 40, white > blacks after 40

family history increases risk by 2-6x

tumor suppressant genes (BRCA1 or BRCA2) increases risk by 4x

benign breast growth increases risk by 2-10x

increased estrogen exposure increases risk by 2x

excessive mammographies - debated !!

mortality decrease in 40-70 year olds

benefits increase with age and fatty breasts

false-negatives + positives

increased unnecessary invasive Tx

increased radiation-induced breast cancer (increased if <30)

against routine screening in 40s, unless high risk (fam history, genes)

screening every 2 years after 50 years

against breast self-examination

tissues (depends on origin)

invasiveness

hormones + genes

lobular carcinoma (in the lobes)

ductal carcinoma (in the ducts)

noninvasive carcinoma (leaves origin and invades other tissues)

invasive carcinoma (stays within origin)

PR+, ER+ : 65-75% (they express the progesterone + estrogen receptors)- require activation of these receptors by estrogen + progesterone for growth

HER2+ : 15-20% (human epithelial subtype 2 receptor, dependent on another form of growth factor)

triple negative : 15% (doesn't express any of these receptors, independent of growth factors for development, BAD)

mutated BCRA1 on chromosome 17 - 55-65%

mutated BCRA2 on chromosome 13- 45%

both tumor suppressor genes

invasive ductal carcinoma type

when you have ductal carcinoma, tumor starts growing in the duct but it is trapped in there by the myo-epithelial layer (they line the ducts)

- possible that tumor will develop mutations or reach a size where its going to break the myo-epithelial capsule

- starts to invade other tissues -> invasive

painless breast lump

edema -> palpable axilas lymph node

ECM destruction -> nipple + skin retraction

lymph nodes

lungs

liver

bones

brain

breast, overlapping, unspecified - 52%

upper-outer quadrant of breast - 25%

2nd most frequently diagnosed worldwide and 6th leading cause of death worldwide

only males - women don't have prostates

often in developed cases countries due to increase in screening and diagnostic technology

75% of cases in males 50+, rare in <50 -> slow growing cancer

most cancers have a good prognosis

old age

family history (BRCA deletions)

ethnicity (African-american)= higher androgen concentration

vasectomy -> debated though (concentration of testosterone has been linked with higher development of prostate cancer)

prostate specific antigen (PSA)

- screen in bloodstream and in urine, more PSA = more prostate

benefits are really small

- only able to decrease the mortality of 1 in 1000 over 11 years

- a lot of false positives

- harms outweighs the benefits for majority

- most undiagnosed men will die of something else

- only on volunteers 50-69 not more than every 4 years

- should be a joint HCP-Patient decision

invading distant issues, not just the seminole vesicles but also entering the colon and nearby adipose tissue

better predictor of prostate cancer, looks at aggressiveness rather than tumor size

- benign prostate hyperplasia is perfect example why this is better

1. small uniform glands

2. more stoma between glands

3. distinctly infiltrative margins

4. irregular masses of neoplastic glands

5. only occasional gland formation

the more differentiated they are as u go down the scale

vast majority of testosterone get converted into inactive products

- some get transformed into estradiol by aromatase and

- some gets transformed into dihydrotestosterone by 5A reductase

testosterone goes down and activity of 5A reductase goes down

dihydrotestosterone goes down

relative percentage of estradiol goes up because aromatase activity doesn't go down

creates an imbalance of ratio of what prostate tissue is used to -> more prostate cancer forming environment

estrogen receptor alpha (ERalpha) are more frequently activated

- prostate inflammation

- estrogen mediated ROS

- mutations and DNA toxicity

repeated inflammation + damage -> genetics/epigenetics alterations -> carcinogenesis

asymptomatic until very advanced

progressive urinary obstruction

large tumor growth -> constipation

bone = 90.1%

lung = 45.7%

greatest killer of both male and females

- difficult to treat and very common

no tools for risk prediction or rate of progression -> difficult to detect

10-15% in active smokers

25% in non-smokers: most often due to smoke exposure, or form of mutations like EGFR or ALK

between 18-20%

cigarette smoking

side stream smoke

asbestos and coal dusts

non-small cell cancer

small cell cancer

squamous cell carcinoma (SCC) = slow growth rate, late metastasis, 30% of LC, associated with smoking

adenocarcinoma = moderate growth rate, early metastasis, 35-40% of LC, associated with family Hx of EGFR mutations

large cell carcinoma (LCC) = rapid growth rate, late metastasis, 10-15% of LC, cells completely undifferentiated

oat cell SCLC = very rapid growth rate, very early metastasis, 15% of LC but 25% of deaths, 5 year survival rate is 5%, strongest association with smoking, neuroendocrine cells -> frequent paraneoplastic syndrome

lung cells acquire neural and endocrine properties

exposure to environmental carcinogens (tobacco smoke, asbestos)

-> DNA damage + airway injuries

-> carcinogenic "hits" mutations + inflammation

-> ROS and even more DNA damage

metaplasia -> carcinoma in situ (stage 1) -> invasive lung cancer -? metastasis (stage 4)

generic symptoms of respiratory conditions: coughing, difficulty breathing, irritation in airways,

SCC: actelectasis and airway obstruction

adenocarcinoma: dyspnea + pleural pain

LCC: airway obstruction -> pneumonia

oat cell carcinoma: paraneoplastic syndrome

brain, bone, liver

metastasis happens via bloodstream, so can spread basically everywhere

includes both colon and rectum cancers

- 78% are colon (bigger surface) and 28% are rectum

3rd most common for males and females

- accounts for 9% of all cancers

incidence is greatest among darker-skinned individuals + high socioeconomic status

median age of diagnosis = 69 years

cell type = adenocarcinoma

polyps (# + size)

inflammatory bowel disease

low fiber/high fat diet

familial adenomatous polyposis (FAP)

mutation

obesity/T2DM

smoking + alcohol

red meat consumption

physical activity

use of NSAIDs

diet high in Vitamin D

cereal + vegetables

postmenopausal estrogen therapy

villous adenoma

- villi cells: absorption of water + electrolytes

tubular adenoma

- tubular cells: secretion of fluids to lubricate colon

the accumulation of genetic mutations

stage 1: 1 or 2 specific mutations, oncogene activation (ex: K-ras)

stage 2: adding mutations, such as tumor suppressor gene APC loss

stage 3: add more mutations, such as loss of TP53

stage 4: metastasis

a lot of smooth muscle cells surrounding the GI tract, harder for tumours to metastasize because they need to penetrate and cross this muscular layer to reach lymphatics + blood vessels

a benign interstitial epithelium mass growing within the GI tract

- the larger the polyp is, the more likely it could develop into cancer (there's more cells)

familial adenomatous polyposis

- familiar condition where individuals form a lot of polyps -> higher risk for colorectal cancer

depends on location, size and shape

transverse colon: pain, obstruction, change in BMs, anemia

descending colon: pain, change in BMs, bright red blood in stool, obstruction

rectum and sigmoid colon: blood in stool, change in BMs, rectal discomfort

ascending colon: pain, mass, change in BM, anemia

lung and liver

3.5 millions new cases/year, likely underreported

light/white skin >>> darker/black skin

increases with age (longer exposure to UV rays)

increase in tanning salons

fair skin

history of sunburns

exposure to sun

high altitude sunny climate

moles on skin

Family history

weak immune system

exposure to radiation

tanning salons

wear clothing

30+ SPF sunscreen

wear a hat

stay in the shade

wear sunglasses

benign tumors

squamous cell carcinoma = most superficial

melanoma = melanoocytes

basal cell carcinoma = basement membrane

nevi (moles)

- benign melanocytic lesions, size + pigmentation varies, anywhere on skin, may transition to melanoma

seborrheic keratosis

- benign basal cell lesions, increases with age, hyperkeratotic scaly appearance, chest back and face

keratoacnthoma

- benign squamous cell tumor, arises from hair follicle, dome-shaped, resolves spontaneously

actinic keratosis

- premalignant lesions (in situ SCC), caused by prolonged UV exposure, felt more than seen, UV protection prevents progression

squamous cell carcinoma = most superficial

melanoma = melanoocytes

basal cell carcinoma = basement membrane

All skin cancers are due to exposure to UV rays, which over time they randomly caused some genetic mutations within the nucleus

- loss of keratinocyte repair + apoptosis resistance

squamous cell carcinoma = TP53 and PTCH1

melanoma = BRAF + Ras

basal cell carcinoma = TP53 and PTCH1

usually confined to epidermis

often occurs on lower lip

firm, elevated, can be granular

can metastasize to regional lymph nodes

irregular margin, change in size + color, bleeding, scab/ulceration

ABCDE screening of nevi

most likely to metastasize

most dangerous !!!

numerous subtypes

slow-growing

firm, often ulcerates + crusts

rarely metastasizes

A = asymmetry

B = border

C = color

D = diameter

E = evolving