Deck 1 Flashcards

1
Q

What are Prevalence estimates in unscreened individuals aged 50 years or older for invasive CRC, in situ carcinoma, adenoma of any size ?

A

Prevalence estimates reveal that in unscreened individuals aged 50 years or older, there is:
a 0.5% to 2.0% chance of harboring an invasive CRC.
a 1.0% to 1.6% chance of an in situ carcinoma,
a 25% to 40% chance of an adenoma of any size.

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2
Q

what is the most influential demographic factor on incidence?

A

Age impacts CRC incidence greater than any other demographic factor.

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3
Q

In what population the incidence incease dramatically? What showed a Surveillance, Epidemiology, and End Results (SEER) program based study?

A

There has been a dramatic increase in younger patients.

A study using data from the Surveillance, Epidemiology, and End Results (SEER) program found a rising incidence of CRC over the last 20 years in patients aged 20 to 49 years. The most pronounced growth was in the age group 40 to 44 years, where colon and rectal cancer increased 56% and 94%, respectively.

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4
Q

What studies reveal the importance of environmental exposure in CRC incidence?

A

Seminal studies have revealed that migrants from low-incident areas to high-incident areas assume the incidence of the host country within one generation.

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5
Q

What changed in the anatomic position for CRC?

A

Classically, colon cancer was believed to be a disease of the left or distal colon. However, the incidence of right-sided or proximal colon cancer has been increasing in North America and Europe.

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6
Q

Give 3 possible explanation to the anotomical shift in CRC?

A

This anatomic shift is likely multifactorial: (1) due to increased longevity; (2) as a response to luminal procarcinogens and carcinogens, which can vary between different sites of the colon and rectum; and (3) because of genetic factors, which can preferentially involve defects in mismatch repair genes with resulting microsatellite instability (MSI) in proximal colon cancers and chromosomal instability pathway predominant in left-sided colon and rectal cancers.

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7
Q

What is the relative risk (RR) for parents and siblings of patients with adenomas compared to spousal controls?
What increase this RR?

A

The relative risk (RR) for parents and siblings of patients with adenomas compared to spousal controls was 1.8, which increased to 2.6 if the proband was younger than age 60 years at adenoma detection.

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8
Q

Is there connection to BRCA1/2 mutations?

A

A new prospective study of 7,105 women followed for a mean of 5.5 years also found an association with the BRCA1 mutation, which conferred increased risk in women younger than 50 years (standardized incidence ratio 3.81). There was no discernible impact of BRCA2 or either mutation in older women.

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9
Q

Whatr is known about obesity and risk of CRC? Is there a gender difference?

A

Increased body mass may result in a twofold increase in CRC risk, with a strong association in men with colon but not rectal cancer. Weight gains during early to middle adulthood have also recently been linked with increased risk of colon but not rectal cancer. This relationship too seems more prominent in men than women in a large prospective study.

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10
Q

Is there a connection between ingestion of meat and risk of CRC? Give non supportive data?

A

Ingestion of red meat but not white meat is associated with an increased CRC risk.

Whether the total abstinence from red meat leads to a decreased CRC incidence has not been clarified, as there are studies with opposing results.Also unclear is whether the type of red meat or the degree of processing or cooking method make any difference.

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11
Q

Is there a connection between coffee consumption and CRC?

A

Caffeinated and decaffeinated coffee drinkers had a decreased risk of colon cancer, particularly of proximal tumors (hazard ratio [HR] for more than six cups a day = 0.62), and decaffeinated coffee drinkers also had a decreased risk of rectal cancer.
Coffee contains numerous bioactive compounds that may modulate cancer risk but previous epidemiologic studies investigating its role in CRC have yielded ambiguous results.

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12
Q

What mechanisms are belived to connect high fiber diet and low incidence of CRC?

A

A high-fiber diet was believed to dilute fecal carcinogens, decrease colon transit time, and generate a favorable luminal environment.

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13
Q

What is one of the most influential study that connect high fiber diet and low incidence of CRC? What this study shows?

A

The European Prospective Investigation into Cancer and Nutrition is an ongoing multicenter prospective cohort study, which was one of the largest and most influential studies to initially report an inverse association between dietary fiber and CRC. More long-term data, with a mean follow-up of 11 years and a near threefold increase in CRC cases, further supports this claim while providing a more precise estimation by fiber food source as well. After multivariable adjustments, total dietary fiber was found to be inversely associated with both colon and rectal cancers (HR per 10 g per day increased in fiber, 0.87), and this did not differ by age, sex, lifestyle, or other dietary factors.

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14
Q

What is non supportive data for the connection between high fiber diet and low incidence of CRC?

A

Other large, well-controlled studies show no inverse
In a study of nearly 90,000 women from ages 34 to 59 years who were followed for 16 years, no protective effect was noted between fiber and incidence of either adenomatous polyp or CRC. This was further corroborated by two large randomized controlled trials that evaluated high-fiber diets.

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15
Q

Is there a connection between Physical inactivity and CRC risk? What is the mechanism? Is there a procective recommendation for physical activity after diagnosis?

A

A sedentary lifestyle may account for an increased CRC risk more for colon then rectal cancer, although the mechanism is unclear.

Data suggest that physical activity after the diagnosis of stages I to III colon cancer may reduce the risk of cancer-related and overall mortality and that the amount of aerobic exercise correlates with a reduced risk of recurrence following resection of stage III colon cancer.

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16
Q

Is alcohol consumption and smoking risk factors for CRC?

A

Most studies of alcohol have demonstrated at most a minimally positive effect. Associations are strongest between alcohol consumption in men and risk of rectal cancer.

Prolonged cigarette smoking is associated with the risk of CRC. Cigarette smoking for > 20 pack-years was associated with large adenoma risk and > 35 pack-years with cancer risk.

17
Q

Is diabetes risk factor for CRC? give two studies that support this connection?

A

Type 2 diabetes has previously been implicated in the development of CRC, but it has been difficult to separate this association from other confounding lifestyle factors such as smoking and obesity.

Yuhara et al. identified 14 studies, most of which controlled for smoking, obesity, and physical exercise, and demonstrated that diabetes was associated with increased risk of both colon and rectal cancer (RR, 1.38, and RR, 1.20, respectively).
A second report, analyzing 24 studies, found a similar association (RR, 1.26) with even higher risk for those patients on insulin therapy (RR, 1.61).

18
Q

Is there a beneficial in NSAIDS use in lynch syndrome?

A

The CAPP2 study, the first double-blind randomized controlled trial of aspirin chemoprevention with cancer as the primary end point. In this study, 861 carriers of Lynch syndrome were randomly assigned to aspirin or placebo. With a mean follow-up of 55.7 months, the authors report a significantly decreased incidence of CRC in the treatment group as well as a trend toward reduction in extracolonic Lynch syndrome– associated cancers.

19
Q

Is there a beneficial in Bisphosphanates use in mCRC?

A

Practical impact on malignant disease, however, has been inconsistent. Singh et al. 78 performed a recent meta-analysis demonstrating a statistically significant 17% reduction in CRC incidence with bisphosphonate use.

20
Q

Is there a beneficial in Statins use in CRC?

A

Epidemiologic studies on CRC have produced very inconsistent results.

21
Q

What is the role of HPV in CRC?

A

Its role in colorectal malignancy is less clear.
In the first meta-analysis to address this topic (including 16 articles and 1,436 patients), Damin et al. not only reported a high prevalence of human papillomavirus (31.9%) in affected patients but also found a strong correlation between human papillomavirus positivity and increased CRC risk (OR, 10.04; 95% CI, 3.7 to 27.5). These results may indicate an alternative pathway of colorectal carcinogenesis that could have vast implications for treatment and prevention.

22
Q

What is the role of E. coli in CRC?

A

Escherichia coli is another pathogen under investigation despite its ubiquity among the gut flora. Studies suggest that the mucosa-adherent or mucosa-internalized strains might play a role in carcinogenesis by inducing chronic inflammation and synthesizing toxins that affect cell proliferation, differentiation, and apoptosis.

23
Q

What incidance of CRC is related to Familial adenomatous polyposis (FAP)? What is the hallmark of this syndrome and the chance of CRC?

A

Familial adenomatous polyposis (FAP) constitutes 1% of all CRC incidence.
Hallmark features include hundreds to thousands of colonic polyps that develop in patients in their teens to 30s, and if the colon is not surgically removed, 100% of patients progress to CRC.

24
Q

What are Extracolonic manifestations of FAP?

A

Benign conditions: congenital hypertrophy of the retinal pigment epithelium, mandibular osteomas, supernumerary teeth, epidermal cysts, adrenal cortical adenomas, desmoid tumors (although these tumors may lead to obstruction).

Malignant conditions: thyroid tumors, gastric/small intestinal polyps with a 5% to 10% risk of duodenal or ampullary adenocarcinoma, and brain tumors (GBM/Medulloblastoma, Turcot Syndrome- Brain tumor + Colonic polyposis (colonic polyps in Turcot syndrome are fewer and larger than in classic FAP).

25
Q

What is the inheritance type to FAP? What is the penetration and de-novo cases?

A

FAP is an autosomally dominant disorder with nearly 100% penetrance. However, about 30% of patients have de novo mutations and are without an ostensible family history.

26
Q

What gene is related to FAP? What is its size?

A

The APC gene comprises 15 exons and encodes a protein of nearly 2,850 amino acids (310 kDa).
Patients with FAP inherit a mutated copy of the APC gene, thereby predisposing them to early-onset polyposis.

27
Q

What incidance of CRC is related to Hereditary nonpolyposis CRC (HNPCC/Lynch syn)?

A

Hereditary nonpolyposis CRC (HNPCC) accounts for about 3% of all CRCs.

28
Q

What are the anatomical features of HNPCC?

A

features include up to 100 colonic polyps (hence the term nonpolyposis), preferentially, albeit not exclusively, in the right or proximal colon.

29
Q

What types of HNPCC exist? what are tye features of each type?

A

HNPCC type I-
there is an accelerated rate of progression to CRC in these diminutive, at times flat, polyps with mean age of onset of CRC being 43 years.

HNPCC type II-
HNPCC type II is distinguished by extracolonic tumors that originate in the stomach, small bowel, bile duct, renal pelvis, ureter, bladder, uterus and ovary, skin, and perhaps the pancreas.

30
Q

What is the life time risk in HNPCC for CRC? endometrial cancer and other cancer at risk?

A

The lifetime risk of CRC in HNPCC is 80%, up to 50% to 60% for endometrial cancer, and 1% to 13% for all other cancers.

31
Q

What is Amsterdam criteria? what are Amsterdam criteria II?

A

Criteria for Identifying At-Risk Individuals for Mismatch Repair Deficiency (High Microsatellite Instability)

Amsterdam II Criteria:
-. At least 3 relatives with HNPCC-associated cancer (colorectal, endometrial, small bowel, ureter, or renal pelvis)
-. At least 2 successive generations should be affected .
-. At least one case before age 50 y.
(+ FAP should be excluded, Tumors should be verified histopathologically).

32
Q

What is Muir-Torre syndrome?

A

A variant of HNPCC involves skin tumors.

33
Q

What is the inheritance type to HNPCC? What is the penetration?

A

HNPCC is an autosomally dominant disorder with about 80% penetrance.

34
Q

What is the genetic defect in HNPCC? how is MSI related?

A

defect in Human mismatch repair genes encode enzymes that repair errors during DNA replication that may occur spontaneously or upon exposure to an exogenous agent (e.g., ultraviolet light, chemical carcinogen).
Mutations in one of these mismatch repair genes results in MSI, which creates a milieu of somatic mutations of target genes— TGF-β2 receptor, bax, IGF type I receptor, among others— in HNPCC-associated tumors.

35
Q

What are the specific genes involved in HNPCC? What is the problem?

A

About 60% of germline mutations in HNPCC are found in either the hMLH1 gene or the hMSH2 gene, but mutations in other members of this family— hMSH6, hPMS1, hPMS2— are rare, thereby indicating that other genes are involved but have yet to be discovered.

36
Q

What is the Genetic Testing in Inherited Colorectal Cancer(FAP, HNPCC)?

A

FAP:
APC protein truncating testing (preferred).
If APC mutation found, screen for mutation in family.
Less desirable alternatives: gene sequencing, linkage testing.

HNPCC:
MSI testing in tumor (aImmunohistochemistry may be an option).
If MSI present, proceed to sequencing of both hMLH1 and hMSH2 genes.
If mutation found, screen for mutation in family.

37
Q

What incidance of CRC is related to Hamartomatous polyposis syndromes?
Give examples of Hamartomatous polyposis syndromes type?

A

Hamartomatous polyposis syndromes are rare syndromes, mostly affecting the pediatric and adolescent population, and represent < 1% of CRCs annually.

  1. Peutz-Jeghers syndrome (LKB1 gene)- involves large but few colonic and small bowel polyps that can manifest by GI bleeding or obstruction and an increased risk of CRC.
  2. Juvenile polyposis (PTEN, SMAD4, BMPR1 genes)- has overlapping clinical manifestations with Peutz-Jeghers, but the polyps tend to be confined to the colon, although cases of gastric and small bowel polyps have been described and there is an increased risk of CRC.
  3. Cowden syndrome(PTEN gene)- harbors hamartomatous polyps anywhere in the GI tract, and surprisingly, there is no increased risk of CRC.