Body size, physical activity, genetic variants in the insulin-like growth factor pathway and colorectal cancer risk

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Abstract

Insulin-like growth factors (IGFs) have been associated with growth, body size, physical activity, and colorectal cancer (CRC). We hypothesized that variants in IGF-related genes increase the CRC susceptibility associated with a larger body size and a lack of physical activity. We assessed this in the Netherlands Cohort Study (NLCS). Participants (n=120 852) completed a baseline questionnaire on diet and cancer. ~75% returned toenail clippings. Using a case-cohort approach and 16.3 years of follow-up, toenail DNA from 3768 subcohort members and 2580 CRC cases was genotyped. We aggregated unfavorable alleles (potentially increasing CRC risk) for 18 single nucleotide polymorphisms in 8 genes into a sum score. The sum score (in tertiles) and an IGF1 19-CA repeat polymorphism (19/19, 19/non-19, and non-19/non-19 repeats) in combination with body size (mostly in tertiles) and (non-)occupational physical activity (>12, 8-12, and <8 kJ/min in the job and >90, >60-90, <30-60, and </=30 min/day) were analyzed by Cox regression. Increasingly higher hazard ratios (HRs) for CRC were observed for a larger adult body mass index, larger trouser size, and tallness in the presence of more unfavorable alleles in men. HRs (95% confidence intervals) for joint effects were 1.55 (1.06-2.25), 1.78 (1.29-2.46), and 1.48 (1.01-2.17), respectively. In women, variant repeat alleles halved CRC risk irrespective of body size and physical activity. No interactions tested significant. To conclude, a larger body size was a CRC risk factor in men in the presence of an accumulation of unfavorable alleles in IGF-related genes, but interactions were nonsignificant.
Original languageEnglish
Pages (from-to)971-981
JournalCarcinogenesis
Volume36
Issue number9
DOIs
Publication statusPublished - 1 Jan 2015

Cite this

@article{95a9b6f17f1943e78fad9540400d7b98,
title = "Body size, physical activity, genetic variants in the insulin-like growth factor pathway and colorectal cancer risk",
abstract = "Insulin-like growth factors (IGFs) have been associated with growth, body size, physical activity, and colorectal cancer (CRC). We hypothesized that variants in IGF-related genes increase the CRC susceptibility associated with a larger body size and a lack of physical activity. We assessed this in the Netherlands Cohort Study (NLCS). Participants (n=120 852) completed a baseline questionnaire on diet and cancer. ~75{\%} returned toenail clippings. Using a case-cohort approach and 16.3 years of follow-up, toenail DNA from 3768 subcohort members and 2580 CRC cases was genotyped. We aggregated unfavorable alleles (potentially increasing CRC risk) for 18 single nucleotide polymorphisms in 8 genes into a sum score. The sum score (in tertiles) and an IGF1 19-CA repeat polymorphism (19/19, 19/non-19, and non-19/non-19 repeats) in combination with body size (mostly in tertiles) and (non-)occupational physical activity (>12, 8-12, and <8 kJ/min in the job and >90, >60-90, <30-60, and </=30 min/day) were analyzed by Cox regression. Increasingly higher hazard ratios (HRs) for CRC were observed for a larger adult body mass index, larger trouser size, and tallness in the presence of more unfavorable alleles in men. HRs (95{\%} confidence intervals) for joint effects were 1.55 (1.06-2.25), 1.78 (1.29-2.46), and 1.48 (1.01-2.17), respectively. In women, variant repeat alleles halved CRC risk irrespective of body size and physical activity. No interactions tested significant. To conclude, a larger body size was a CRC risk factor in men in the presence of an accumulation of unfavorable alleles in IGF-related genes, but interactions were nonsignificant.",
author = "C.C.J.M. Simons and L.J. Schouten and R. Godschalk and {van Engeland}, M. and {van den Brandt}, P.A. and {van Schooten}, F.J. and M.P. Weijenberg",
year = "2015",
month = "1",
day = "1",
doi = "10.1093/carcin/bgv077",
language = "English",
volume = "36",
pages = "971--981",
journal = "Carcinogenesis",
issn = "0143-3334",
publisher = "Oxford University Press",
number = "9",

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TY - JOUR

T1 - Body size, physical activity, genetic variants in the insulin-like growth factor pathway and colorectal cancer risk

AU - Simons, C.C.J.M.

AU - Schouten, L.J.

AU - Godschalk, R.

AU - van Engeland, M.

AU - van den Brandt, P.A.

AU - van Schooten, F.J.

AU - Weijenberg, M.P.

PY - 2015/1/1

Y1 - 2015/1/1

N2 - Insulin-like growth factors (IGFs) have been associated with growth, body size, physical activity, and colorectal cancer (CRC). We hypothesized that variants in IGF-related genes increase the CRC susceptibility associated with a larger body size and a lack of physical activity. We assessed this in the Netherlands Cohort Study (NLCS). Participants (n=120 852) completed a baseline questionnaire on diet and cancer. ~75% returned toenail clippings. Using a case-cohort approach and 16.3 years of follow-up, toenail DNA from 3768 subcohort members and 2580 CRC cases was genotyped. We aggregated unfavorable alleles (potentially increasing CRC risk) for 18 single nucleotide polymorphisms in 8 genes into a sum score. The sum score (in tertiles) and an IGF1 19-CA repeat polymorphism (19/19, 19/non-19, and non-19/non-19 repeats) in combination with body size (mostly in tertiles) and (non-)occupational physical activity (>12, 8-12, and <8 kJ/min in the job and >90, >60-90, <30-60, and </=30 min/day) were analyzed by Cox regression. Increasingly higher hazard ratios (HRs) for CRC were observed for a larger adult body mass index, larger trouser size, and tallness in the presence of more unfavorable alleles in men. HRs (95% confidence intervals) for joint effects were 1.55 (1.06-2.25), 1.78 (1.29-2.46), and 1.48 (1.01-2.17), respectively. In women, variant repeat alleles halved CRC risk irrespective of body size and physical activity. No interactions tested significant. To conclude, a larger body size was a CRC risk factor in men in the presence of an accumulation of unfavorable alleles in IGF-related genes, but interactions were nonsignificant.

AB - Insulin-like growth factors (IGFs) have been associated with growth, body size, physical activity, and colorectal cancer (CRC). We hypothesized that variants in IGF-related genes increase the CRC susceptibility associated with a larger body size and a lack of physical activity. We assessed this in the Netherlands Cohort Study (NLCS). Participants (n=120 852) completed a baseline questionnaire on diet and cancer. ~75% returned toenail clippings. Using a case-cohort approach and 16.3 years of follow-up, toenail DNA from 3768 subcohort members and 2580 CRC cases was genotyped. We aggregated unfavorable alleles (potentially increasing CRC risk) for 18 single nucleotide polymorphisms in 8 genes into a sum score. The sum score (in tertiles) and an IGF1 19-CA repeat polymorphism (19/19, 19/non-19, and non-19/non-19 repeats) in combination with body size (mostly in tertiles) and (non-)occupational physical activity (>12, 8-12, and <8 kJ/min in the job and >90, >60-90, <30-60, and </=30 min/day) were analyzed by Cox regression. Increasingly higher hazard ratios (HRs) for CRC were observed for a larger adult body mass index, larger trouser size, and tallness in the presence of more unfavorable alleles in men. HRs (95% confidence intervals) for joint effects were 1.55 (1.06-2.25), 1.78 (1.29-2.46), and 1.48 (1.01-2.17), respectively. In women, variant repeat alleles halved CRC risk irrespective of body size and physical activity. No interactions tested significant. To conclude, a larger body size was a CRC risk factor in men in the presence of an accumulation of unfavorable alleles in IGF-related genes, but interactions were nonsignificant.

U2 - 10.1093/carcin/bgv077

DO - 10.1093/carcin/bgv077

M3 - Article

VL - 36

SP - 971

EP - 981

JO - Carcinogenesis

JF - Carcinogenesis

SN - 0143-3334

IS - 9

ER -