# Câncer colorretal hereditário sem polipose

> Página oficial: https://raras.org/doenca/cancer-colorretal-hereditario-sem-polipose
> Fonte: Raras.org — Banco de Dados de Doenças Raras em Português (CC BY-NC-SA 4.0)
> Última atualização: 2026-05-07

## Identificadores

- **ORPHA**: 443909 — https://www.orpha.net/en/disease/detail/443909
- **OMIM**: none — https://omim.org/entry/none

## Descrição clínica

Uma condição que aumenta o risco de ter câncer, caracterizada pelo desenvolvimento de câncer colorretal (de intestino grosso) que não está ligado à polipose colorretal (uma condição com muitos pólipos no intestino), câncer de endométrio (no útero) e vários outros tipos de câncer (como o de ovário, estômago, vias biliares, intestino delgado e vias urinárias), e que, geralmente, são diagnosticados em idade precoce.

## Epidemiologia e herança


## Sinais e sintomas (72 fenótipos HPO)

- **Comportamento atípico** — HPO: HP:0000708
- **Convulsão** — HPO: HP:0001250
- **Carcinoma de mama** — HPO: HP:0003002
- **Neoplasia da pele** — HPO: HP:0008069
- **Enxaqueca** — HPO: HP:0002076
- **Câncer de estômago** — HPO: HP:0012126
- **Neoplasia do fígado** — HPO: HP:0002896
- **Discinesia** — HPO: HP:0100660
- **Neoplasia do sistema esquelético** — HPO: HP:0010622
- **Adenocarcinoma pancreático** — HPO: HP:0006725
- **Neoplasia benigna do trato geniturinário** — HPO: HP:0006778
- **Adenocarcinoma duodenal** — HPO: HP:0006771
- **Carcinoma laríngeo** — HPO: HP:0012118
- **Má absorção** — HPO: HP:0002024
- **Neoplasia ovariana** — HPO: HP:0100615
- **Defeito do campo visual** — HPO: HP:0001123
- **Anormalidade do metabolismo da creatina** — HPO: HP:0012113
- **Transtorno do déficit de atenção com hiperatividade** — HPO: HP:0007018
- **Aumento da pressão intracraniana** — HPO: HP:0002516
- **Parestesia** — HPO: HP:0003401
- **Polipose intestinal** — HPO: HP:0200008
- **Alucinações** — HPO: HP:0000738
- **Câncer de cólon** — HPO: HP:0003003
- **Neoplasia do trato urinário** — HPO: HP:0010786
- **Neoplasia do reto** — HPO: HP:0100743
- **Divertículos colônicos** — HPO: HP:0002253
- **Carcinoma de glândula sebácea** — HPO: HP:0030410
- **Adenoma sebáceo** — HPO: HP:0009720
- **Agnosia** — HPO: HP:0010524
- **Neoplasia da mama** — HPO: HP:0100013
- **Adenoma hipofisário** — HPO: HP:0002893
- **Constipação** — HPO: HP:0002019
- **Dor abdominal** — HPO: HP:0002027
- **Náusea e vômito** — HPO: HP:0002017
- **Neuroblastoma** — HPO: HP:0003006
- **Comprometimento da memória** — HPO: HP:0002354
- **Disgrafia** — HPO: HP:0010526
- **Neoplasia do cólon** — HPO: HP:0100273
- **Sinal piramidal anormal** — HPO: HP:0007256
- **Neoplasia de glândula salivar** — HPO: HP:0100684
- _...e mais 32 sintomas. Ver https://raras.org/doenca/cancer-colorretal-hereditario-sem-polipose._

## Genes associados (20)

- **ATM** — Serine-protein kinase ATM [Candidate gene tested in]
  - Função: Serine/threonine protein kinase which activates checkpoint signaling upon double strand breaks (DSBs), apoptosis and genotoxic stresses such as ionizing ultraviolet A light (UVA), thereby acting as a
- **MSH6** — DNA mismatch repair protein Msh6 [Disease-causing germline mutation(s) in]
  - Função: Component of the post-replicative DNA mismatch repair system (MMR). Heterodimerizes with MSH2 to form MutS alpha, which binds to DNA mismatches thereby initiating DNA repair. When bound, MutS alpha be
- **PMS1** — PMS1 protein homolog 1 [Candidate gene tested in]
  - Função: Probably involved in the repair of mismatches in DNA
- **POLD1** — DNA polymerase delta catalytic subunit [Candidate gene tested in]
  - Função: As the catalytic component of the trimeric (Pol-delta3 complex) and tetrameric DNA polymerase delta complexes (Pol-delta4 complex), plays a crucial role in high fidelity genome replication, including
- **MUTYH** — Adenine DNA glycosylase [Candidate gene tested in]
  - Função: Involved in oxidative DNA damage repair. Initiates repair of A*oxoG to C*G by removing the inappropriately paired adenine base from the DNA backbone. Possesses both adenine and 2-OH-A DNA glycosylase
- **CHEK2** — Serine/threonine-protein kinase Chk2 [Candidate gene tested in]
  - Função: Serine/threonine-protein kinase which is required for checkpoint-mediated cell cycle arrest, activation of DNA repair and apoptosis in response to the presence of DNA double-strand breaks. May also ne
- **MSH2** — DNA mismatch repair protein Msh2 [Disease-causing germline mutation(s) in]
  - Função: Component of the post-replicative DNA mismatch repair system (MMR). Forms two different heterodimers: MutS alpha (MSH2-MSH6 heterodimer) and MutS beta (MSH2-MSH3 heterodimer) which binds to DNA mismat
- **PIK3CA** — Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [Candidate gene tested in]
  - Função: Phosphoinositide-3-kinase (PI3K) phosphorylates phosphatidylinositol (PI) and its phosphorylated derivatives at position 3 of the inositol ring to produce 3-phosphoinositides (PubMed:15135396, PubMed:
- **RPS20** — Small ribosomal subunit protein uS10 [Candidate gene tested in]
  - Função: Component of the small ribosomal subunit (PubMed:23636399). The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell (PubMed:23636399)
- **BRCA2** — Breast cancer type 2 susceptibility protein [Candidate gene tested in]
  - Função: Involved in double-strand break repair and/or homologous recombination. Binds RAD51 and potentiates recombinational DNA repair by promoting assembly of RAD51 onto single-stranded DNA (ssDNA). Acts by
- **MLH1** — DNA mismatch repair protein Mlh1 [Disease-causing germline mutation(s) in]
  - Função: Heterodimerizes with PMS2 to form MutL alpha, a component of the post-replicative DNA mismatch repair system (MMR). DNA repair is initiated by MutS alpha (MSH2-MSH6) or MutS beta (MSH2-MSH3) binding t
- **SEMA4A** — Semaphorin-4A [Candidate gene tested in]
  - Função: Cell surface receptor for PLXNB1, PLXNB2, PLXNB3 and PLXND1 that plays an important role in cell-cell signaling (By similarity). Regulates glutamatergic and GABAergic synapse development (By similarit
- **NPAT** — Protein NPAT [Candidate gene tested in]
  - Função: Transcription regulator required for progression through the G1 and S phases of the cell cycle and for S phase entry (PubMed:12665581, PubMed:15555599, PubMed:9472014). Acts as a key transcription reg
- **MLH3** — DNA mismatch repair protein Mlh3 [Disease-causing germline mutation(s) in]
  - Função: Probably involved in the repair of mismatches in DNA
- **PMS2** — Mismatch repair endonuclease PMS2 [Disease-causing germline mutation(s) in]
  - Função: Component of the post-replicative DNA mismatch repair system (MMR) (PubMed:30653781, PubMed:35189042). Heterodimerizes with MLH1 to form MutL alpha. DNA repair is initiated by MutS alpha (MSH2-MSH6) o

## Medicamentos em desenvolvimento (6)

- ASPIRIN — Fase Phase 3 (Cyclooxygenase inhibitor)
- BEVACIZUMAB — Fase Phase 3 (Vascular endothelial growth factor A inhibitor)
- FLUOROURACIL — Fase Phase 3 (Thymidylate synthase inhibitor)
- MESALAMINE — Fase Phase 2 (Arachidonate 5-lipoxygenase inhibitor)
- NAPROXEN — Fase Phase 1 (Cyclooxygenase inhibitor)
- ATORVASTATIN — Fase Phase 0.5 (HMG-CoA reductase inhibitor)
- Fonte: https://platform.opentargets.org/disease/MONDO_0018630

## Ensaios clínicos ativos (5)

- **NCT07472686** [RECRUITING]: Small Bowel Capsule Endoscopy in Lynch Syndrome — https://clinicaltrials.gov/study/NCT07472686
- **NCT02012699** [RECRUITING]: Integrated Cancer Repository for Cancer Research — https://clinicaltrials.gov/study/NCT02012699
- **NCT03702309** [RECRUITING]: Liquid Biopsy Evaluation and Repository Development at Princess Margaret — https://clinicaltrials.gov/study/NCT03702309
- **NCT05677048** [ACTIVE_NOT_RECRUITING]: Feasibility Study: IGNITE-TX (Identifying Individuals for Genetic Testing & Treatment) Intervention — https://clinicaltrials.gov/study/NCT05677048
- **NCT07436312** [NOT_YET_RECRUITING]: Impact of Consumption of Ultra-processed Foods in Individuals at High Risk of Cancer — https://clinicaltrials.gov/study/NCT07436312
- **NCT06426927** [COMPLETED]: PeLear CCC: Proyecto Latino Contra Cancer Colorrectal — https://clinicaltrials.gov/study/NCT06426927

## Doenças relacionadas (por similaridade fenotípica)

- [NÃO RARA NA EUROPA: Câncer colorretal](https://raras.org/doenca/nao-rara-na-europa-cancer-colorretal) — ORPHA:466667 — 72 sintomas em comum
- [Síndrome Lynch](https://raras.org/doenca/sindrome-lynch) — ORPHA:144 — 62 sintomas em comum
- [Câncer colorretal familiar, tipo X](https://raras.org/doenca/cancer-colorretal-familiar-tipo-x) — ORPHA:440437 — 53 sintomas em comum
- [Síndrome neurológico paraneoplásico](https://raras.org/doenca/sindrome-neurologico-paraneoplasico) — ORPHA:36388 — 18 sintomas em comum
- [Tumor endócrino enteropancreático](https://raras.org/doenca/tumor-endocrino-enteropancreatico) — ORPHA:100092 — 17 sintomas em comum
- [Doença de Behçet](https://raras.org/doenca/doenca-de-behcet) — ORPHA:117 — 16 sintomas em comum
- [Síndrome distonia-plus](https://raras.org/doenca/sindrome-distonia-plus) — ORPHA:98203 — 16 sintomas em comum
- [Porfiria hepática](https://raras.org/doenca/porfiria-hepatica) — ORPHA:659694 — 15 sintomas em comum
- [Neoplasias endócrinas múltiplas](https://raras.org/doenca/neoplasias-endocrinas-multiplas) — ORPHA:100094 — 15 sintomas em comum
- [Neoplasia neuroendócrina do pâncreas](https://raras.org/doenca/506052) — ORPHA:506052 — 15 sintomas em comum

## Importante

O Raras **não diagnostica e não prescreve**. Esta página é educativa e informativa.
Pacientes devem consultar profissionais de saúde qualificados para decisões clínicas.

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**Citação sugerida**: Raras.org — Câncer colorretal hereditário sem polipose. Disponível em: https://raras.org/doenca/cancer-colorretal-hereditario-sem-polipose
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