GPAtlas🧭 When to suspect (and when to refer for genetic assessment)
Lynch syndrome is the commonest inherited cause of colorectal cancer. It is an autosomal dominant condition caused by:
• A germline pathogenic variant in a DNA mismatch repair (MMR) gene – MLH1, MSH2, MSH6 or PMS2
• A 3′ deletion of EPCAM that silences MSH2
Loss of mismatch repair allows replication errors to accumulate, driving early, often multiple cancers. Around 1 in 400 people carry a Lynch variant, yet fewer than 5% are diagnosed.
The lifetime risk of colorectal cancer and (in women) endometrial cancer is markedly raised, frequently before the age of 50, alongside increased risk of these cancers:
• Ovarian
• Gastric
• Small-bowel
• Hepatobiliary
• Urinary-tract (ureter/renal pelvis)
• Pancreatic
• Brain and skin
• Prostate cancer in men
In primary care:
• Recognise who warrants referral to clinical genetics from the family or personal history
• In anyone with known Lynch syndrome, never attribute new symptoms to a benign cause
Genetic testing is not initiated in primary care – the GP refers.
• All colorectal cancers and all endometrial cancers are now reflex-tested for Lynch at diagnosis in secondary care.
• For an at-risk person without a personal cancer, the GP assesses the family history and refers.
| Trigger | Typical pattern | Primary-care action |
|---|---|---|
| Known familial variant | Pathogenic MMR or EPCAM variant identified in a relative | Refer to clinical genetics for predictive (cascade) testing |
| Personal Lynch cancer | Personal diagnosis of colorectal or endometrial cancer | • Reflex tumour testing is arranged in secondary care • Confirm it has happened |
| High-risk family history | ≥ 3 relatives with Lynch-spectrum cancer across ≥ 2 generations (≥ 1 a first-degree relative) | Refer to clinical genetics |
| Moderate-risk family history | One first-degree relative with colorectal cancer aged < 50, or two first-degree relatives with colorectal cancer at any age | Refer for specialist risk assessment or clinical genetics |
| Lynch-spectrum cluster | Family cluster of endometrial, ovarian, gastric, urothelial, small-bowel or pancreaticobiliary cancer | Refer to clinical genetics |
Source: NICE DG27 · NICE DG42 · BSG
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