Review
Is right-sided colon cancer different to left-sided colorectal cancer? – A systematic review

https://doi.org/10.1016/j.ejso.2014.11.001Get rights and content

Abstract

Colorectal cancer (CRC) exhibits differences in incidence, pathogenesis, molecular pathways and outcome depending on the location of the tumor. This review focuses on the latest developments in epidemiological and scientific studies, which have enhanced our understanding on the underlying genetic and immunological differences between the proximal (right-sided) colon and the distal (left-sided) colorectum. The different ways in which environmental risk factors influence the pathogenesis of CRC depending on its location and the variations in surgical and oncological outcomes are also discussed in this review. In the current era of personalized medicine, we aim to reiterate the importance of tumor location in management of CRC and the implication on future clinical and scientific research.

Introduction

In the current era of personalized medicine, colorectal cancer (CRC) is no longer regarded as a single entity. Colorectal cancer research has concentrated on providing more effective treatment, resulting in advancement in the knowledge of the genetic and molecular mechanism of carcinogenesis.

Bufill et al. started describing CRC depending on the anatomical site.1 This was an attempt to sub-classify CRC as clinical data showed disparities in incidence and outcome between right-sided and left-sided colon cancer. Subsequent research has described the distinct differences in epidemiology, pathogenesis, genetic and epigenetic alterations, molecular pathways and outcome depending on the anatomical site of tumor. Currently, there is a general consensus that anatomical site is an important factor in management of CRC.

In this review, we aim to present the recent findings and discuss the implications for future research in CRC. For the purposes of this review, proximal or right-sided colon cancer (RCC) will consist of cancers of the caecum, ascending and transverse colon up to the splenic flexure, and distal or left-sided colorectal cancer (LCRC) will consist of cancers of the descending and sigmoid colon and rectum, unless specified.

We performed a systematic review with reference to preferred reporting items for systematic reviews and meta-analysis (PRISMA).2 We identified relevant articles by searching EMBASE, MEDLINE, and Pubmed using a search strategy to identify reports with a combination of controlled vocabulary and text words related to ‘colon’ and ‘colorectum’ (neoplasia, carcinoma, tumor, metastasis, malignancy), and to ‘site’ or ‘subsite’. Searches and cross-references were carried out using a ‘similar articles’ function and hand searches of articles identified. We included all adult human studies in English, published between September 1947 and January 2014. We identified all journal articles that assessed colorectal cancer classification by site in relation to prevalence, presentation, genetic, molecular aspects, immunology, environmental factors, and outcomes (long-term survival and oncological outcome). We did not include conference abstracts due to the insufficient data provided. We also manually explored the reference lists of the included studies for additional supporting articles.

Data were extracted by three independent reviewers (GHL, GM, AA). When recent meta-analyses or systematic reviews were identified, the included studies were not reported individually. Meta-analyses were prioritized, when available. To limit the number of references, the most relevant observational studies were selected. Studies discussing pathophysiological mechanisms were assessed in a narrative way, aiming to balance the arguments for and against different genetic, molecular and immunological hypotheses.

Section snippets

Results

From 394 initial citations, we included 6 meta-analyses, 12 reviews, 62 observational studies and 7 additional supporting articles (see Fig. 1).

Conclusion

As is evident from recent epidemiological studies, the prevalence of RCC is on the rise compared to LCRC, and we have explored various factors leading to differences in presentation and clinical outcome in CRC depending on its subsite (see Fig. 3). This could be attributed to the differences in anatomical, acquired and inherited factors leading to different molecular pathways in the pathogenesis of CRC.

We have also mentioned the complexities and potential challenges in management of CRC. It is

Author's contribution

GHL – conception, literature search and drafted article.

GM/AA – literature search and drafted article on epidemiology section.

HOA/DBO – literature search and drafted article on immunology.

SKC – critically reviewed manuscript and final approval of the version to be published.

Conflict of interest

Authors declare no conflict of interest.

Acknowledgment

HOA was supported by a grant from the Association for International Cancer Research (AICR), (12-0234) Scotland.

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