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

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 VatandoustAmanda 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

College of Medicine and Public Health

Research output: Contribution to journal › Article › peer-review

22 Citations (Scopus)

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.

Original language	English
Pages (from-to)	131-138
Number of pages	8
Journal	Asia-Pacific Journal of Clinical Oncology
Volume	17
Issue number	1
Early online date	3 Sept 2020
DOIs	https://doi.org/10.1111/ajco.13428
Publication status	Published - Feb 2021

Keywords

colorectal cancer
germline mutations
risk factors
screening
type 2 diabetes
young-onset colorectal cancer

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1111/ajco.13428Licence: In Copyright

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Mikaeel, R. R., Symonds, E. L., Kimber, J., Smith, E., Horsnell, M., Uylaki, W., Tapia Rico, G., Hewett, P. J., Yong, J., Tonkin, D., Jesudason, D., Poplawski, N. K., Ruszkiewicz, A. R., Drew, P. A., Hardingham, J. E., Wong, S., Frank, O., Tomita, Y., Patel, D., ... Young, J. P. (2021). Young-onset colorectal cancer is associated with a personal history of type 2 diabetes. Asia-Pacific Journal of Clinical Oncology, 17(1), 131-138. https://doi.org/10.1111/ajco.13428

@article{fc6e495063704fe4bcb1bbef6a0778aa,

title = "Young-onset colorectal cancer is associated with a personal history of type 2 diabetes",

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",

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

year = "2021",

month = feb,

doi = "10.1111/ajco.13428",

language = "English",

volume = "17",

pages = "131--138",

journal = "Asia-Pacific Journal of Clinical Oncology",

issn = "1743-7555",

publisher = "Blackwell Publishing Ltd",

number = "1",

}

Mikaeel, RR, Symonds, EL, Kimber, J, Smith, E, Horsnell, M, Uylaki, W, Tapia Rico, G, Hewett, PJ, Yong, J, Tonkin, D, Jesudason, D, Poplawski, NK, Ruszkiewicz, AR, Drew, PA, Hardingham, JE, Wong, S, Frank, O, Tomita, Y, Patel, D, Vatandoust, S, Townsend, AR, Roder, D, Young, GP, Parry, S, Tomlinson, IP, Wittert, G, Wattchow, D, Worthley, DL, Brooks, WJ, Price, TJ & Young, JP 2021, 'Young-onset colorectal cancer is associated with a personal history of type 2 diabetes', Asia-Pacific Journal of Clinical Oncology, vol. 17, no. 1, pp. 131-138. https://doi.org/10.1111/ajco.13428

TY - JOUR

T1 - Young-onset colorectal cancer is associated with a personal history of type 2 diabetes

AU - Mikaeel, Reger R.

AU - Symonds, Erin L.

AU - Kimber, James

AU - Smith, Eric

AU - Horsnell, Mehgan

AU - Uylaki, Wendy

AU - Tapia Rico, Gonzalo

AU - Hewett, Peter J.

AU - Yong, Jonathan

AU - Tonkin, Darren

AU - Jesudason, David

AU - Poplawski, Nicola K.

AU - Ruszkiewicz, Andrew R.

AU - Drew, Paul A.

AU - Hardingham, Jenny E.

AU - Wong, Stephanie

AU - Frank, Oliver

AU - Tomita, Yoko

AU - Patel, Dainik

AU - Vatandoust, Sina

AU - Townsend, Amanda R.

AU - Roder, David

AU - Young, Graeme P.

AU - Parry, Susan

AU - Tomlinson, Ian P.

AU - Wittert, Gary

AU - Wattchow, David

AU - Worthley, Daniel L.

AU - Brooks, William J.

AU - Price, Timothy J.

AU - Young, Joanne P.

PY - 2021/2

Y1 - 2021/2

N2 - 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.

AB - 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.

KW - colorectal cancer

KW - germline mutations

KW - risk factors

KW - screening

KW - type 2 diabetes

KW - young-onset colorectal cancer

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U2 - 10.1111/ajco.13428

DO - 10.1111/ajco.13428

M3 - Article

AN - SCOPUS:85090113020

SN - 1743-7555

VL - 17

SP - 131

EP - 138

JO - Asia-Pacific Journal of Clinical Oncology

JF - Asia-Pacific Journal of Clinical Oncology

IS - 1

ER -

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

Abstract

Keywords

UN SDGs

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