The role of family history in colorectal cancer screening in East Asia

Abstract

Background Globally, colorectal cancer is one of the leading causes of cancer related death. Asia has had relatively low incidence rates of colorectal cancer when compared with western countries. Over the last decade, however, occurrences have increased in many Asian countries. In East Asia, colorectal cancer incidence has been increasing over the last few decades; however, many countries are still lack of strategies on colorectal cancer screening. Colorectal cancer screening guidelines in many Western countries use family history information when assigning people into different risk categories to recommend for frequency and intensity of screening strategies. However, the relationship between family history and colorectal cancer and adenoma risk has not been well studied in Asian countries. Given that family structure and environmental exposures are likely to be different in Asian countries it is assumed, the association may also prove to be different.

Aims This thesis aimed to investigate the role of family history of colorectal cancer in colorectal cancer screening in East Asian countries.

Method This thesis includes the following five studies addressing the gaps in knowledge of the role of family history in colorectal cancer screening strategies. The main database for this thesis is the prospective data of 175,000 men and women from three countries (Japan, Korea, and China) who have been recruited into the Asia Cohort Consortium (ACC, https://www.asiacohort.org/). 1. A literature review of current colorectal cancer screening guidelines in Asian countries. 2. A systematic review of studies on the association between family history of colorectal cancer and the risk of colorectal cancer in Asian countries. 3. A pooled analysis of six prospective cohorts from Asia Cohort Consortium to investigate the association between family history of colorectal cancer and the incidence of colorectal cancer in Asian countries 4. A pooled analysis of six prospective cohorts from Asia Cohort Consortium to investigate the association between family history of colorectal cancer and the mortality of colorectal cancer in Asian countries 5. External validation of the Asian-Pacific Colorectal Cancer Screening (APCS) Score using six prospective cohorts from Asia Cohort Consortium.

Results Firstly, from the meta-analysis, the association of colorectal neoplasia with having at least one first-degree relative family history of colorectal cancer differed by Asian region: being 1.69 (1.46, 1.96) for East Asia; 3.44 (2.32, 5.10) for Western Asia and 5.14 (2.44, 10.8) for South-Eastern Asia. The strength of associations between family history of colorectal cancer and the risk of colorectal cancer and adenoma for East Asia was similar to that of Western populations but higher for Western and South-Eastern Asia. This information will be useful to triage the populations in Asian countries for colorectal cancer screening by the strength of family history in different regions of Asia. Secondly, with the pooled analysis of exist data from the Asia cohort consortium, the family history of colorectal cancer associated with a higher risk of incidence of colorectal cancer in Asian countries. Thirdly, the evidence from family history and mortality, this is no evidence for an association between family history of colorectal cancer and overall survival or colorectal cancer-specific mortality. However, specific mechanisms underlying family history may have a prognostic impact and merit further study. Future studies need to collect data on possible confounders of the effect, such as tumor stage at diagnosis, presence of multiple cancers, mode of presentation to hospital, and surgical or clinical management in order to produce more conclusive results. Last, the APCS scores were efficient to identify individuals with a high risk of colorectal cancer in the East Asia population.

Conclusions This thesis has generated new knowledge about family history and the risk of colorectal cancer in East Asia. The systematic review and meta-analysis demonstrate that there is large heterogeneity in the association with colorectal neoplasia with having at least one first-degree relative family history of colorectal cancer differed by Asian regions. Family history could be a useful tool for colorectal cancer screening program but might not be associated with the mortality of colorectal cancer. APCS scores can effectively identify individuals with a high risk of colorectal cancer in East Asia. The feasibility and acceptability of the APCS score to the general population in Asia will need to be further examined.