COMPREHENSIVE STUDY NOTES: GENOME
MAINTENANCE MECHANISMS & CANCER
SUSCEPTIBILITY
INTRODUCTION TO GENOME MAINTENANCE
Genome maintenance ensures DNA integrity, preventing accumulation of mutations that can lead to cancer.
DNA damage can occur due to:
• Environmental factors: UV, chemicals, radiation
• Internal factors: replication errors, reactive oxygen species
Cells have multiple repair pathways to detect and correct damage before it leads to malignant transformation.
COLON CANCER: FAP VS. HNPCC
FAMILIAL ADENOMATOUS POLYPOSIS (FAP)
Etiology: Mutation in the APC tumor suppressor gene.
Clinical Features:
• Hundreds to thousands of adenomatous polyps in colon and rectum
• Onset: Adolescence or early adulthood
• Risk: Almost 100% chance of developing colorectal cancer by age 40–50 if untreated
• Management: Regular colonoscopy; prophylactic colectomy may be recommended.
HEREDITARY NONPOLYPOSIS COLORECTAL CANCER
(HNPCC /LYNCH SYNDROME)
Etiology: Defective mismatch repair (MMR) genes (MLH1, MSH2, MSH6, PMS2).
, Clinical Features:
• Few polyps, but higher chance of rapid malignant transformation
• Often right-sided colon cancer
• Increased risk of other cancers: endometrial, ovarian, gastric
• Screening: Colonoscopy from age 20–25; genetic testing recommended for family members.
COMPARATIVE TABLE: FAP VS. HNPCC
Feature FAP HNPCC
Polyps Hundreds to thousands Few
Growth rate Slow Rapid
Main genes APC MLH1, MSH2, MSH6, PMS2
Cancer onset Adolescence Adulthood
Other cancer risk Upper GI polyps Endometrial, ovarian, gastric
Screening Colonoscopy, prophylactic colectomy Colonoscopy, genetic counseling
This Photo by Unknown Author is licensed under CC BY
MAINTENANCE MECHANISMS & CANCER
SUSCEPTIBILITY
INTRODUCTION TO GENOME MAINTENANCE
Genome maintenance ensures DNA integrity, preventing accumulation of mutations that can lead to cancer.
DNA damage can occur due to:
• Environmental factors: UV, chemicals, radiation
• Internal factors: replication errors, reactive oxygen species
Cells have multiple repair pathways to detect and correct damage before it leads to malignant transformation.
COLON CANCER: FAP VS. HNPCC
FAMILIAL ADENOMATOUS POLYPOSIS (FAP)
Etiology: Mutation in the APC tumor suppressor gene.
Clinical Features:
• Hundreds to thousands of adenomatous polyps in colon and rectum
• Onset: Adolescence or early adulthood
• Risk: Almost 100% chance of developing colorectal cancer by age 40–50 if untreated
• Management: Regular colonoscopy; prophylactic colectomy may be recommended.
HEREDITARY NONPOLYPOSIS COLORECTAL CANCER
(HNPCC /LYNCH SYNDROME)
Etiology: Defective mismatch repair (MMR) genes (MLH1, MSH2, MSH6, PMS2).
, Clinical Features:
• Few polyps, but higher chance of rapid malignant transformation
• Often right-sided colon cancer
• Increased risk of other cancers: endometrial, ovarian, gastric
• Screening: Colonoscopy from age 20–25; genetic testing recommended for family members.
COMPARATIVE TABLE: FAP VS. HNPCC
Feature FAP HNPCC
Polyps Hundreds to thousands Few
Growth rate Slow Rapid
Main genes APC MLH1, MSH2, MSH6, PMS2
Cancer onset Adolescence Adulthood
Other cancer risk Upper GI polyps Endometrial, ovarian, gastric
Screening Colonoscopy, prophylactic colectomy Colonoscopy, genetic counseling
This Photo by Unknown Author is licensed under CC BY
