To Investigate Risk of Colorectal Neoplasms in First-degree Relatives of Patients With Non-advanced Adenomas
Condition: Colorectal Cancer; Colorectal Adenoma
MeSH terms: Neoplasms; Colorectal Neoplasms; Adenoma
Study type: Observational

Summary: 
      The risk of CRC in families of patients with CRC is well established, but it is less
      well-defined for families of patients with adenomas. Screening recommendations to families
      when an index subject has an adenoma on colonoscopy are not clear. Previous studies
      demonstrating an increased CRC risk in close relatives of subjects with adenomas were mostly
      limited by the lack of a suitable comparison group, did not offer colonoscopy to all
      relatives or did not have verification on true status of adenoma history in the relatives. A
      systematic review has reported that most studies cited for risk of CRC in relatives with
      adenomas have not addressed the intended question. Currently International guidelines
      recommended screening colonoscopy in close relatives and at a younger age when there is a
      proband with an adenoma, however this recommendation has not been fully supported by all
      societies due to the lack of robust evidence. This gap in knowledge highlights the need of
      well-designed and adequately powered studies to estimate the risk of colorectal neoplasms in
      subjects who have first-degree relatives with adenomas.

      Up to 30% of average risk asymptomatic individuals 50 years or older will have at least one
      adenoma. Based on current guidelines, nearly half the population will be counseled to undergo
      a colonoscopy from 40 years old based on a positive family history of adenoma. This will have
      enormous burden on the healthcare system if screening is implicated in all these individuals.
      Secondly, not all adenomas carry the same risk. Large or villous adenomas are associated with
      a nearly 70% increased risk of CRC in first degree relatives (FDR) whereas small adenomas may
      be associated with a modest increased risk 19. It is therefore important to determine the
      risk of colorectal neoplasms in families of subjects with non-advanced adenomas to justify
      more intensive screening in these individuals. Investigators hypothesize that first-degree
      relatives of patients with non-advanced adenoma have an increased risk of both CRC and
      adenomas. Investigators aim to quantify this risk, and to identify other individual patient
      or neoplasm characteristics that may contribute to this increased risk. In addition,
      Investigators aim to determine molecular alteration profiles of colonic adenoma in siblings
      of patients with advanced neoplasm.
    

Detailed description: 
      Colorectal cancer (CRC) is the third most common cancer and second leading cause of cancer
      death worldwide. Based on data from the Hong Kong Cancer Registry in 2012, CRC is the second
      most common cancer in Hong Kong. It is one of the few cancers for which there are convincing
      data to support the benefits of screeColorectal cancer (CRC) is the third most common cancer
      and second leading cause of cancer death worldwide. Based on data from the Hong Kong Cancer
      Registry in 2012, CRC is the second most common cancer in Hong Kong. It is one of the few
      cancers for which there are convincing data to support the benefits of screening. Currently
      the removal of adenomas is the most effective way in reducing cancer incidence and mortality.
      International guidelines recommend screening for individuals at an average risk of CRC from
      the age of 50 years.

      Up to 30% of average risk asymptomatic individuals 50 years or older will have at least one
      adenoma. Based on current guidelines, nearly half the population will be counseled to undergo
      a colonoscopy from 40 years old based on a positive family history of adenoma. This will have
      enormous burden on the healthcare system if screening is implicated in all these individuals.
      Secondly, not all adenomas carry the same risk. Large or villous adenomas are associated with
      a nearly 70% increased risk of CRC in first degree relatives (FDR) whereas small adenomas may
      be associated with a modest increased risk. It is therefore important to determine the risk
      of colorectal neoplasms in families of subjects with non-advanced adenomas to justify more
      intensive screening in these individuals.

      The molecular pathways leading to tumour development in familial colorectal neoplasms are
      likely to be different from sporadic cases. Development of new molecular based methods for
      early detection, prevention or treatment relies heavily on the understanding of the
      differences between sporadic and familial neoplasms. Identification of genetic mutations can
      also improve genetic diagnosis and screening protocol of an at risk population.

      Investigators hypothesize that first-degree relatives of patients with non-advanced adenoma
      have an increased risk of both CRC and adenomas. Investigators aim to quantify this risk, and
      to identify other individual patient or neoplasm characteristics that may contribute to this
      increased risk. In addition, Investigators aim to determine molecular alteration profiles of
      colonic adenoma in siblings of patients with advanced neoplasm.

      The risk of CRC in families of patients with CRC is well established, but it is less
      well-defined for families of patients with adenomas. Screening recommendations to families
      when an index subject has an adenoma on colonoscopy are not clear. Previous studies
      demonstrating an increased CRC risk in close relatives of subjects with adenomas were mostly
      limited by the lack of a suitable comparison group, did not offer colonoscopy to all
      relatives or did not have verification on true status of adenoma history in the relatives. A
      systematic review has reported that most studies cited for risk of CRC in relatives with
      adenomas have not addressed the intended question. Currently International guidelines
      recommended screening colonoscopy in close relatives and at a younger age when there is a
      proband with an adenoma, however this recommendation has not been fully supported by all
      societies due to the lack of robust evidence. This gap in knowledge highlights the need of
      well-designed and adequately powered studies to estimate the risk of colorectal neoplasms in
      subjects who have first-degree relatives with adenomas.
    

Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        siblings of Hong Kong Chinese patients with advanced neoplasm compared with a sex and
        age-matched control population
      
Biospecimen description: 
      stool, colonic mucosa