Hereditary non-polyposis colorectal cancer (HNPCC) has an increased risk of all the following except
**Core Concept**
Hereditary non-polyposis colorectal cancer (HNPCC), also known as Lynch syndrome, is caused by mutations in DNA mismatch repair genes (e.g., MLH1, MSH2, MSH6, PMS2). This leads to microsatellite instability and a significantly increased risk of early-onset cancers in multiple organs, particularly the colorectum, endometrium, and ovary.
**Why the Correct Answer is Right**
HNPCC predisposes individuals to colorectal, endometrial, and ovarian cancers due to defective DNA repair. The endometrium and ovary are highly susceptible because of their rapid cell turnover and exposure to hormonal stimuli. Gastric cancer risk is also elevated, especially in certain populations (e.g., Japanese), due to *H. pylori* interaction and genetic susceptibility. However, the pancreas is not a major site of increased risk in Lynch syndrome. While pancreatic cancer may occur in Lynch patients, the association is weak and not considered a hallmark or significantly elevated risk compared to other organs.
**Why Each Wrong Option is Incorrect**
Option A: Endometrium – Correctly associated with HNPCC; endometrial cancer is one of the most common extracolonic manifestations.
Option B: Ovary – Ovarian cancer is a well-documented risk in Lynch syndrome, especially in women with *MLH1* or *MSH2* mutations.
Option C: Stomach – Increased risk of gastric cancer, particularly in certain ethnic groups, due to genetic predisposition and *H. pylori* interaction.
Option D: Pancreas – This is the **exception**; while rare pancreatic cancers may occur, the risk is not significantly elevated compared to the general population and is not a hallmark of HNPCC.
**Clinical Pearl / High-Yield Fact**
Remember: **"Lynch = Colorectal, Endometrium, Ovary, Stomach"** – the pancreas is not a major site. Always screen women with HNPCC for endometrial and ovarian cancers, and consider gastric screening in high-risk populations.
✓ Correct Answer: D. Pancreas