Familial Risk and Heritability of Colorectal Cancer in the Nordic Twin Study of Cancer

Rebecca E Graff, Sören Möller, Michael N Passarelli, John S Witte, Axel Skytthe, Kaare Christensen, Qihua Tan, Hans-Olov Adami, Kamila Czene, Jennifer R. Harris, Eero Pukkala, Jaakko Kaprio, Edward Giovannucci, Lorelei A Mucci, Jacob B Hjelmborg

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

BACKGROUND & AIMS: We analyzed data from twins to determine how much the familial risk of colorectal cancer can be attributed to genetic factors vs environment. We also examined whether heritability is distinct for colon vs rectal cancer, given evidence of distinct etiologies.

METHODS: Our data set included 39,990 monozygotic and 61,443 same-sex dizygotic twins from the Nordic Twin Study of Cancer. We compared each cancer's risk in twins of affected co-twins relative to the cohort risk (familial risk ratio; FRR). We then estimated the proportion of variation in risk that could be attributed to genetic factors (heritability).

RESULTS: From earliest registration in 1943 through 2010, 1861 individuals were diagnosed with colon cancer and 1268 with rectal cancer. Monozygotic twins of affected co-twins had an FRR for colorectal cancer of 3.1 (95% CI, 2.4-3.8) relative to the cohort risk. Dizygotic twins of affected co-twins had an FRR for colorectal cancer of 2.2 (95% CI, 1.7-2.7). We estimated that 40% (95% CI, 33%-48%) of the variation in colorectal cancer risk could be attributed to genetic factors; unique environment only accounted for the remaining liability. For colon cancer, the FRR was 3.3 (95% CI, 2.1-4.5) for monozygotic twins and 2.6 (95% CI, 1.7-3.5) for dizygotic twins. For rectal cancer, comparable estimates were 3.3 (95% CI, 1.5-5.1) for monozygotic twins and 2.6 (95% CI, 1.2-4.0) for dizygotic twins. Heritability estimates for colon and rectal cancer were 16% (95% CI, 0-46%) and 15% (95% CI, 0-50%), common environment estimates were 15% (95% CI, 0-38%) and 11% (95% CI, 0-38%), and unique environment estimates were 68% (95% CI, 57%-79%) and 75% (95% CI, 61%-88%), respectively.

CONCLUSION: Inter-individual genetic differences could account for 40% of the variation in susceptibility to colorectal cancer; risk for colon and rectal cancers might have less of a genetic component than risk for colorectal cancer. Siblings, and particularly monozygotic co-twins, of individuals with colon or rectal cancer should consider personalized screening.

Original languageEnglish
JournalClinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association
Volume15
Issue number8
Pages (from-to)1256-1264
ISSN1542-3565
DOIs
Publication statusPublished - 2017

Fingerprint

Twin Studies
Colorectal Neoplasms
Rectal Neoplasms
Dizygotic Twins
Monozygotic Twins
Colonic Neoplasms
Neoplasms
Individuality
Siblings
Colon
Odds Ratio

Keywords

  • Biometric modeling
  • Concordance relative risk
  • genetic susceptibility
  • Zygosity

Cite this

Graff, Rebecca E ; Möller, Sören ; Passarelli, Michael N ; Witte, John S ; Skytthe, Axel ; Christensen, Kaare ; Tan, Qihua ; Adami, Hans-Olov ; Czene, Kamila ; Harris, Jennifer R. ; Pukkala, Eero ; Kaprio, Jaakko ; Giovannucci, Edward ; Mucci, Lorelei A ; Hjelmborg, Jacob B. / Familial Risk and Heritability of Colorectal Cancer in the Nordic Twin Study of Cancer. In: Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association. 2017 ; Vol. 15, No. 8. pp. 1256-1264.
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title = "Familial Risk and Heritability of Colorectal Cancer in the Nordic Twin Study of Cancer",
abstract = "BACKGROUND & AIMS: We analyzed data from twins to determine how much the familial risk of colorectal cancer can be attributed to genetic factors vs environment. We also examined whether heritability is distinct for colon vs rectal cancer, given evidence of distinct etiologies.METHODS: Our data set included 39,990 monozygotic and 61,443 same-sex dizygotic twins from the Nordic Twin Study of Cancer. We compared each cancer's risk in twins of affected co-twins relative to the cohort risk (familial risk ratio; FRR). We then estimated the proportion of variation in risk that could be attributed to genetic factors (heritability).RESULTS: From earliest registration in 1943 through 2010, 1861 individuals were diagnosed with colon cancer and 1268 with rectal cancer. Monozygotic twins of affected co-twins had an FRR for colorectal cancer of 3.1 (95{\%} CI, 2.4-3.8) relative to the cohort risk. Dizygotic twins of affected co-twins had an FRR for colorectal cancer of 2.2 (95{\%} CI, 1.7-2.7). We estimated that 40{\%} (95{\%} CI, 33{\%}-48{\%}) of the variation in colorectal cancer risk could be attributed to genetic factors; unique environment only accounted for the remaining liability. For colon cancer, the FRR was 3.3 (95{\%} CI, 2.1-4.5) for monozygotic twins and 2.6 (95{\%} CI, 1.7-3.5) for dizygotic twins. For rectal cancer, comparable estimates were 3.3 (95{\%} CI, 1.5-5.1) for monozygotic twins and 2.6 (95{\%} CI, 1.2-4.0) for dizygotic twins. Heritability estimates for colon and rectal cancer were 16{\%} (95{\%} CI, 0-46{\%}) and 15{\%} (95{\%} CI, 0-50{\%}), common environment estimates were 15{\%} (95{\%} CI, 0-38{\%}) and 11{\%} (95{\%} CI, 0-38{\%}), and unique environment estimates were 68{\%} (95{\%} CI, 57{\%}-79{\%}) and 75{\%} (95{\%} CI, 61{\%}-88{\%}), respectively.CONCLUSION: Inter-individual genetic differences could account for 40{\%} of the variation in susceptibility to colorectal cancer; risk for colon and rectal cancers might have less of a genetic component than risk for colorectal cancer. Siblings, and particularly monozygotic co-twins, of individuals with colon or rectal cancer should consider personalized screening.",
keywords = "Biometric modeling, Concordance relative risk, genetic susceptibility, Zygosity, biometric modeling, concordance relative risk, genetic susceptibility, zygosity",
author = "Graff, {Rebecca E} and S{\"o}ren M{\"o}ller and Passarelli, {Michael N} and Witte, {John S} and Axel Skytthe and Kaare Christensen and Qihua Tan and Hans-Olov Adami and Kamila Czene and Harris, {Jennifer R.} and Eero Pukkala and Jaakko Kaprio and Edward Giovannucci and Mucci, {Lorelei A} and Hjelmborg, {Jacob B}",
note = "Copyright {\circledC} 2017 AGA Institute. Published by Elsevier Inc. All rights reserved.",
year = "2017",
doi = "10.1016/j.cgh.2016.12.041",
language = "English",
volume = "15",
pages = "1256--1264",
journal = "Clinical Gastroenterology and Hepatology",
issn = "1542-3565",
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number = "8",

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Familial Risk and Heritability of Colorectal Cancer in the Nordic Twin Study of Cancer. / Graff, Rebecca E; Möller, Sören; Passarelli, Michael N; Witte, John S; Skytthe, Axel; Christensen, Kaare; Tan, Qihua; Adami, Hans-Olov; Czene, Kamila; Harris, Jennifer R.; Pukkala, Eero; Kaprio, Jaakko; Giovannucci, Edward; Mucci, Lorelei A; Hjelmborg, Jacob B.

In: Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association, Vol. 15, No. 8, 2017, p. 1256-1264.

Research output: Contribution to journalJournal articleResearchpeer-review

TY - JOUR

T1 - Familial Risk and Heritability of Colorectal Cancer in the Nordic Twin Study of Cancer

AU - Graff, Rebecca E

AU - Möller, Sören

AU - Passarelli, Michael N

AU - Witte, John S

AU - Skytthe, Axel

AU - Christensen, Kaare

AU - Tan, Qihua

AU - Adami, Hans-Olov

AU - Czene, Kamila

AU - Harris, Jennifer R.

AU - Pukkala, Eero

AU - Kaprio, Jaakko

AU - Giovannucci, Edward

AU - Mucci, Lorelei A

AU - Hjelmborg, Jacob B

N1 - Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved.

PY - 2017

Y1 - 2017

N2 - BACKGROUND & AIMS: We analyzed data from twins to determine how much the familial risk of colorectal cancer can be attributed to genetic factors vs environment. We also examined whether heritability is distinct for colon vs rectal cancer, given evidence of distinct etiologies.METHODS: Our data set included 39,990 monozygotic and 61,443 same-sex dizygotic twins from the Nordic Twin Study of Cancer. We compared each cancer's risk in twins of affected co-twins relative to the cohort risk (familial risk ratio; FRR). We then estimated the proportion of variation in risk that could be attributed to genetic factors (heritability).RESULTS: From earliest registration in 1943 through 2010, 1861 individuals were diagnosed with colon cancer and 1268 with rectal cancer. Monozygotic twins of affected co-twins had an FRR for colorectal cancer of 3.1 (95% CI, 2.4-3.8) relative to the cohort risk. Dizygotic twins of affected co-twins had an FRR for colorectal cancer of 2.2 (95% CI, 1.7-2.7). We estimated that 40% (95% CI, 33%-48%) of the variation in colorectal cancer risk could be attributed to genetic factors; unique environment only accounted for the remaining liability. For colon cancer, the FRR was 3.3 (95% CI, 2.1-4.5) for monozygotic twins and 2.6 (95% CI, 1.7-3.5) for dizygotic twins. For rectal cancer, comparable estimates were 3.3 (95% CI, 1.5-5.1) for monozygotic twins and 2.6 (95% CI, 1.2-4.0) for dizygotic twins. Heritability estimates for colon and rectal cancer were 16% (95% CI, 0-46%) and 15% (95% CI, 0-50%), common environment estimates were 15% (95% CI, 0-38%) and 11% (95% CI, 0-38%), and unique environment estimates were 68% (95% CI, 57%-79%) and 75% (95% CI, 61%-88%), respectively.CONCLUSION: Inter-individual genetic differences could account for 40% of the variation in susceptibility to colorectal cancer; risk for colon and rectal cancers might have less of a genetic component than risk for colorectal cancer. Siblings, and particularly monozygotic co-twins, of individuals with colon or rectal cancer should consider personalized screening.

AB - BACKGROUND & AIMS: We analyzed data from twins to determine how much the familial risk of colorectal cancer can be attributed to genetic factors vs environment. We also examined whether heritability is distinct for colon vs rectal cancer, given evidence of distinct etiologies.METHODS: Our data set included 39,990 monozygotic and 61,443 same-sex dizygotic twins from the Nordic Twin Study of Cancer. We compared each cancer's risk in twins of affected co-twins relative to the cohort risk (familial risk ratio; FRR). We then estimated the proportion of variation in risk that could be attributed to genetic factors (heritability).RESULTS: From earliest registration in 1943 through 2010, 1861 individuals were diagnosed with colon cancer and 1268 with rectal cancer. Monozygotic twins of affected co-twins had an FRR for colorectal cancer of 3.1 (95% CI, 2.4-3.8) relative to the cohort risk. Dizygotic twins of affected co-twins had an FRR for colorectal cancer of 2.2 (95% CI, 1.7-2.7). We estimated that 40% (95% CI, 33%-48%) of the variation in colorectal cancer risk could be attributed to genetic factors; unique environment only accounted for the remaining liability. For colon cancer, the FRR was 3.3 (95% CI, 2.1-4.5) for monozygotic twins and 2.6 (95% CI, 1.7-3.5) for dizygotic twins. For rectal cancer, comparable estimates were 3.3 (95% CI, 1.5-5.1) for monozygotic twins and 2.6 (95% CI, 1.2-4.0) for dizygotic twins. Heritability estimates for colon and rectal cancer were 16% (95% CI, 0-46%) and 15% (95% CI, 0-50%), common environment estimates were 15% (95% CI, 0-38%) and 11% (95% CI, 0-38%), and unique environment estimates were 68% (95% CI, 57%-79%) and 75% (95% CI, 61%-88%), respectively.CONCLUSION: Inter-individual genetic differences could account for 40% of the variation in susceptibility to colorectal cancer; risk for colon and rectal cancers might have less of a genetic component than risk for colorectal cancer. Siblings, and particularly monozygotic co-twins, of individuals with colon or rectal cancer should consider personalized screening.

KW - Biometric modeling

KW - Concordance relative risk

KW - genetic susceptibility

KW - Zygosity

KW - biometric modeling

KW - concordance relative risk

KW - genetic susceptibility

KW - zygosity

U2 - 10.1016/j.cgh.2016.12.041

DO - 10.1016/j.cgh.2016.12.041

M3 - Journal article

VL - 15

SP - 1256

EP - 1264

JO - Clinical Gastroenterology and Hepatology

JF - Clinical Gastroenterology and Hepatology

SN - 1542-3565

IS - 8

ER -