Young-onset colorectal cancer is associated with a personal history of type 2 diabetes

Reger R Mikaeel; Erin L Symonds; James Kimber; Eric Smith; Mehgan Horsnell; Wendy Uylaki; Gonzalo Tapia Rico; Peter J Hewett; Jonathan Yong; Darren Tonkin; David Jesudason; Nicola K Poplawski; Andrew R Ruszkiewicz; Paul A Drew; Jenny E Hardingham; Stephanie Wong; Oliver Frank; Yoko Tomita; Dainik Patel; Sina Vatandoust; Amanda R Townsend; David Roder; Graeme P Young; Susan Parry; Ian P Tomlinson; Gary Wittert; David Wattchow; Daniel L Worthley; William J Brooks; Timothy J Price; Joanne P Young

doi:10.1111/ajco.13428

Young-onset colorectal cancer is associated with a personal history of type 2 diabetes

Asia Pac J Clin Oncol. 2021 Feb;17(1):131-138. doi: 10.1111/ajco.13428. Epub 2020 Sep 3.

Authors

Reger R Mikaeel^{1

2

3

4}, Erin L Symonds^{5

6}, James Kimber³, Eric Smith^{1

7}, Mehgan Horsnell¹, Wendy Uylaki^{1

8}, Gonzalo Tapia Rico⁹, Peter J Hewett⁷, Jonathan Yong⁷, Darren Tonkin⁷, David Jesudason¹⁰, Nicola K Poplawski^{11

12}, Andrew R Ruszkiewicz^{13

14}, Paul A Drew⁷, Jenny E Hardingham^{1

2

3}, Stephanie Wong¹⁵, Oliver Frank¹⁶, Yoko Tomita¹, Dainik Patel^{3

17}, Sina Vatandoust¹⁸, Amanda R Townsend¹, David Roder¹⁹, Graeme P Young⁶, Susan Parry^{20

21}, Ian P Tomlinson²², Gary Wittert²³, David Wattchow²⁴, Daniel L Worthley²⁵, William J Brooks²⁶, Timothy J Price^{1

3}, Joanne P Young^{1

2

3}

Affiliations

¹ Department of Haematology and Oncology, The Queen Elizabeth Hospital, Woodville South, South Australia, Australia.
² SAHMRI Colorectal Node, Basil Hetzel Institute, Woodville South, South Australia, Australia.
³ Faculty of Health and Medical Sciences, University of Adelaide, Adelaide, South Australia, Australia.
⁴ Biology Department, College of Science, University of Duhok, Duhok, Kurdistan, Iraq.
⁵ Bowel Health Service, Flinders Medical Centre, Bedford Park, South Australia, Australia.
⁶ Flinders Centre for Innovation in Cancer, Flinders University, Bedford Park, South Australia, Australia.
⁷ University of Adelaide Department of Surgery, The Queen Elizabeth Hospital, Woodville South, South Australia, Australia.
⁸ Department of Gastroenterology, The Queen Elizabeth Hospital, Woodville South, South Australia, Australia.
⁹ Department of Medical Oncology, Royal Adelaide Hospital, Adelaide, Australia.
¹⁰ Department of Endocrinology, The Queen Elizabeth Hospital, Woodville South, South Australia, Australia.
¹¹ Adult Genetics Unit, Royal Adelaide Hospital, Adelaide, South Australia, Australia.
¹² Discipline of Paediatrics, Adelaide Medical School, Faculty of Health and Medical Sciences, University of Adelaide, Adelaide, South Australia, Australia.
¹³ Division of Anatomical Pathology, SA Pathology, Adelaide, South Australia, Australia.
¹⁴ Centre for Cancer Biology, University of South Australia, Adelaide, South Australia, Australia.
¹⁵ Department of Gastroenterology and Hepatology, Royal Adelaide Hospital, Adelaide, Australia.
¹⁶ Discipline of General Practice, Adelaide Medical School, Faculty of Health and Medical Sciences, University of Adelaide, Adelaide, South Australia, Australia.
¹⁷ Department of Medical Oncology, Lyell McEwin Hospital, Elizabeth Vale, South Australia, Australia.
¹⁸ Flinders Medical Centre, Bedford Park, South Australia, Australia.
¹⁹ Cancer Epidemiology and Population Health, University of South Australia, Adelaide, South Australia, Australia.
²⁰ New Zealand Familial GI Cancer Service, Auckland City Hospital, Auckland, New Zealand.
²¹ National Bowel Screening Programme, Ministry of Health, New Zealand.
²² Institute of Cancer and Genomic Sciences, University of Birmingham, Edgbaston, Birmingham, United Kingdom.
²³ Discipline of Medicine, Faculty of Health and Medical Sciences, University of Adelaide, Adelaide, South Australia, Australia.
²⁴ Flinders University, Flinders Medical Centre, Bedford Park, South Australia, Australia.
²⁵ South Australian Health & Medical Research Institute & School of Medicine, The University of Adelaide, Adelaide, South Australia, Australia.
²⁶ Adelaide Medical Solutions, Adelaide Health Solutions, Woodville, South Australia, Australia.

PMID: 32885561
DOI: 10.1111/ajco.13428

Abstract

Background: Colorectal cancer (CRC) is rising in incidence in young adults, and this observation is currently unexplained. We investigated whether having a personal history of type 2 diabetes mellitus (T2D) was a potential risk factor for young-onset colorectal cancer (YOCRC).

Methods: The South Australian Young Onset (SAYO) CRC study is a series of young adults with CRC below age 55. Ninety unrelated YOCRC cases were recruited to the study. Personal history and detailed family history of T2D were obtained at face-to-face interview and confirmed from medical records. Whole exome sequencing was conducted on germline DNA from each CRC case. Controls for personal history studies of T2D were 240 patients with proven clear colonoscopies and no known CRC predispositions.

Results: The median age of YOCRC cases was 44 years (18-54) and of controls was 45 years (18-54), and 53% of both cases and controls were females (P = 0.99). Left-sided (distal) CRC was seen in 67/89 (75%) of cases. A personal history of T2D was confirmed in 17/90 (19%) YOCRC patients compared with controls (12/240, 5%; P < 0.001; odds ratio = 4.4; 95% confidence interval, 2.0-9.7). YOCRC patients frequently reported at least one first-degree relative with T2D (32/85, 38%). Ten of 87 (12%) of YOCRC cases had CRC-related pathogenic germline variants, however, no pathogenic variants in familial diabetes-associated genes were seen.

Conclusions: Though the mechanism remains unclear, our observations suggest that there is enrichment for personal history of T2D in YOCRC patients.

Impact: A diagnosis of T2D could therefore potentially identify a subset of young adults at increased risk for CRC and in whom early screening might be appropriate.

Keywords: colorectal cancer; germline mutations; risk factors; screening; type 2 diabetes; young-onset colorectal cancer.

MeSH terms

Adolescent
Adult
Age of Onset
Australia
Colorectal Neoplasms / etiology*
Colorectal Neoplasms / pathology
Diabetes Mellitus, Type 2 / complications*
Female
Genotype
Humans
Male
Middle Aged
Risk Factors
Young Adult