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

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

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, there were 1861 individuals diagnosed with colon cancer and 1268 diagnosed with rectal cancer. Monozygotic twins of affected co-twins had an FRR for colorectal cancer of 3.1 (95% confidence interval [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. Conclusions Interindividual 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.

OriginalsprogEngelsk
TidsskriftClinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association
Vol/bind15
Udgave nummer8
Sider (fra-til)1256-1264
ISSN1542-3565
DOI
StatusUdgivet - aug. 2017

Fingeraftryk

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

Emneord

  • biometric modeling
  • concordance relative risk
  • genetic susceptibility
  • zygosity

Citer dette

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. I: Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association. 2017 ; Bind 15, Nr. 8. s. 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, there were 1861 individuals diagnosed with colon cancer and 1268 diagnosed with rectal cancer. Monozygotic twins of affected co-twins had an FRR for colorectal cancer of 3.1 (95{\%} confidence interval [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. Conclusions Interindividual 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, Biometric Modeling, Concordance Relative Risk, Genetic Susceptibility, Rectal Neoplasms/epidemiology, Humans, Middle Aged, Twins, Dizygotic, Child, Preschool, Colonic Neoplasms/epidemiology, Family Health, Infant, Male, Young Adult, Europe/epidemiology, Aged, 80 and over, Adult, Female, Child, Genetic Predisposition to Disease, Risk Assessment, Twins, Monozygotic, Adolescent, Individuality, Aged",
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",
month = "8",
doi = "10.1016/j.cgh.2016.12.041",
language = "English",
volume = "15",
pages = "1256--1264",
journal = "Clinical Gastroenterology and Hepatology",
issn = "1542-3565",
publisher = "W.B.Saunders Co.",
number = "8",

}

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.

I: Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association, Bind 15, Nr. 8, 08.2017, s. 1256-1264.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer 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 - 2017/8

Y1 - 2017/8

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, there were 1861 individuals diagnosed with colon cancer and 1268 diagnosed with rectal cancer. Monozygotic twins of affected co-twins had an FRR for colorectal cancer of 3.1 (95% confidence interval [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. Conclusions Interindividual 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, there were 1861 individuals diagnosed with colon cancer and 1268 diagnosed with rectal cancer. Monozygotic twins of affected co-twins had an FRR for colorectal cancer of 3.1 (95% confidence interval [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. Conclusions Interindividual 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

KW - Biometric Modeling

KW - Concordance Relative Risk

KW - Genetic Susceptibility

KW - Rectal Neoplasms/epidemiology

KW - Humans

KW - Middle Aged

KW - Twins, Dizygotic

KW - Child, Preschool

KW - Colonic Neoplasms/epidemiology

KW - Family Health

KW - Infant

KW - Male

KW - Young Adult

KW - Europe/epidemiology

KW - Aged, 80 and over

KW - Adult

KW - Female

KW - Child

KW - Genetic Predisposition to Disease

KW - Risk Assessment

KW - Twins, Monozygotic

KW - Adolescent

KW - Individuality

KW - Aged

U2 - 10.1016/j.cgh.2016.12.041

DO - 10.1016/j.cgh.2016.12.041

M3 - Journal article

C2 - 28130150

VL - 15

SP - 1256

EP - 1264

JO - Clinical Gastroenterology and Hepatology

JF - Clinical Gastroenterology and Hepatology

SN - 1542-3565

IS - 8

ER -