Body mass index in early adulthood and colorectal cancer risk for carriers and non-carriers of germline mutations in DNA mismatch repair genes

A. K. Win; J. G. Dowty; D. R. English; P. T. Campbell; J. P. Young; I. Winship; F. A. MacRae; L. Lipton; S. Parry; G. P. Young; D. D. Buchanan; M. E. Martínez; E. T. Jacobs; D. J. Ahnen; R. W. Haile; G. Casey; J. A. Baron; N. M. Lindor; S. N. Thibodeau; P. A. Newcomb; J. D. Potter; L. Le Marchand; S. Gallinger; J. L. Hopper; M. A. Jenkins

doi:10.1038/bjc.2011.172

Body mass index in early adulthood and colorectal cancer risk for carriers and non-carriers of germline mutations in DNA mismatch repair genes

A. K. Win, J. G. Dowty, D. R. English, P. T. Campbell, J. P. Young, I. Winship, F. A. MacRae, L. Lipton, S. Parry, G. P. Young, D. D. Buchanan, M. E. Martínez, E. T. Jacobs, D. J. Ahnen, R. W. Haile, G. Casey, J. A. Baron, N. M. Lindor, S. N. Thibodeau, P. A. NewcombJ. D. Potter, L. Le Marchand, S. Gallinger, J. L. Hopper, M. A. Jenkins

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

48 Scopus citations

Abstract

Background:Carriers of germline mutations in DNA mismatch repair (MMR) genes have a high risk of colorectal cancer (CRC), but the modifiers of this risk are not well established. We estimated an association between body mass index (BMI) in early adulthood and subsequent risk of CRC for carriers and, as a comparison, estimated the association for non-carriers.Methods:A weighted Cox regression was used to analyse height and weight at 20 years reported by 1324 carriers of MMR gene mutations (500 MLH1, 648 MSH2, 117 MSH6 and 59 PMS2) and 1219 non-carriers from the Colon Cancer Family Registry.Results:During 122 304 person-years of observation, we observed diagnoses of CRC for 659 carriers (50%) and 36 non-carriers (3%). For carriers, the risk of CRC increased by 30% for each 5 kg m-2 increment in BMI in early adulthood (hazard ratio, HR: 1.30; 95% confidence interval, CI: 1.08-1.58; P0.01), and increased by 64% for non-carriers (HR: 1.64; 95% CI: 1.02-2.64; P0.04) after adjusting for sex, country, cigarette smoking and alcohol drinking (and the MMR gene that was mutated in carriers). The difference in HRs for carriers and non-carriers was not statistically significant (P0.50). For MLH1 and PMS2 (MutLα heterodimer) mutation carriers combined, the corresponding increase was 36% (HR: 1.36; 95% CI: 1.05-1.76; P0.02). For MSH2 and MSH6 (MutSα heterodimer) mutation carriers combined, the HR was 1.26 (95% CI: 0.96-1.65; P0.09). There was no significant difference between the HRs for MutLα and MutSα heterodimer carriers (P0.56).Conclusion:Body mass index in early adulthood is positively associated with risk of CRC for MMR gene mutation carriers and non-carriers.

Original language	English (US)
Pages (from-to)	162-169
Number of pages	8
Journal	British Journal of Cancer
Volume	105
Issue number	1
DOIs	https://doi.org/10.1038/bjc.2011.172
State	Published - Jun 28 2011
Externally published	Yes

Keywords

body mass index
colorectal cancer
mismatch repair gene

ASJC Scopus subject areas

Oncology
Cancer Research

UN SDGs

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

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10.1038/bjc.2011.172

Cite this

Win, A. K., Dowty, J. G., English, D. R., Campbell, P. T., Young, J. P., Winship, I., MacRae, F. A., Lipton, L., Parry, S., Young, G. P., Buchanan, D. D., Martínez, M. E., Jacobs, E. T., Ahnen, D. J., Haile, R. W., Casey, G., Baron, J. A., Lindor, N. M., Thibodeau, S. N., ... Jenkins, M. A. (2011). Body mass index in early adulthood and colorectal cancer risk for carriers and non-carriers of germline mutations in DNA mismatch repair genes. British Journal of Cancer, 105(1), 162-169. https://doi.org/10.1038/bjc.2011.172

Win, AK, Dowty, JG, English, DR, Campbell, PT, Young, JP, Winship, I, MacRae, FA, Lipton, L, Parry, S, Young, GP, Buchanan, DD, Martínez, ME, Jacobs, ET, Ahnen, DJ, Haile, RW, Casey, G, Baron, JA, Lindor, NM, Thibodeau, SN, Newcomb, PA, Potter, JD, Le Marchand, L, Gallinger, S, Hopper, JL & Jenkins, MA 2011, 'Body mass index in early adulthood and colorectal cancer risk for carriers and non-carriers of germline mutations in DNA mismatch repair genes', British Journal of Cancer, vol. 105, no. 1, pp. 162-169. https://doi.org/10.1038/bjc.2011.172

@article{2d5ecf5ec2f84d119eca45b950da68d2,

title = "Body mass index in early adulthood and colorectal cancer risk for carriers and non-carriers of germline mutations in DNA mismatch repair genes",

abstract = "Background:Carriers of germline mutations in DNA mismatch repair (MMR) genes have a high risk of colorectal cancer (CRC), but the modifiers of this risk are not well established. We estimated an association between body mass index (BMI) in early adulthood and subsequent risk of CRC for carriers and, as a comparison, estimated the association for non-carriers.Methods:A weighted Cox regression was used to analyse height and weight at 20 years reported by 1324 carriers of MMR gene mutations (500 MLH1, 648 MSH2, 117 MSH6 and 59 PMS2) and 1219 non-carriers from the Colon Cancer Family Registry.Results:During 122 304 person-years of observation, we observed diagnoses of CRC for 659 carriers (50%) and 36 non-carriers (3%). For carriers, the risk of CRC increased by 30% for each 5 kg m-2 increment in BMI in early adulthood (hazard ratio, HR: 1.30; 95% confidence interval, CI: 1.08-1.58; P0.01), and increased by 64% for non-carriers (HR: 1.64; 95% CI: 1.02-2.64; P0.04) after adjusting for sex, country, cigarette smoking and alcohol drinking (and the MMR gene that was mutated in carriers). The difference in HRs for carriers and non-carriers was not statistically significant (P0.50). For MLH1 and PMS2 (MutLα heterodimer) mutation carriers combined, the corresponding increase was 36% (HR: 1.36; 95% CI: 1.05-1.76; P0.02). For MSH2 and MSH6 (MutSα heterodimer) mutation carriers combined, the HR was 1.26 (95% CI: 0.96-1.65; P0.09). There was no significant difference between the HRs for MutLα and MutSα heterodimer carriers (P0.56).Conclusion:Body mass index in early adulthood is positively associated with risk of CRC for MMR gene mutation carriers and non-carriers.",

keywords = "body mass index, colorectal cancer, mismatch repair gene",

author = "Win, {A. K.} and Dowty, {J. G.} and English, {D. R.} and Campbell, {P. T.} and Young, {J. P.} and I. Winship and MacRae, {F. A.} and L. Lipton and S. Parry and Young, {G. P.} and Buchanan, {D. D.} and Mart{\'i}nez, {M. E.} and Jacobs, {E. T.} and Ahnen, {D. J.} and Haile, {R. W.} and G. Casey and Baron, {J. A.} and Lindor, {N. M.} and Thibodeau, {S. N.} and Newcomb, {P. A.} and Potter, {J. D.} and {Le Marchand}, L. and S. Gallinger and Hopper, {J. L.} and Jenkins, {M. A.}",

note = "Funding Information: This work was supported by the National Cancer Institute, National Institutes of Health under RFA #CA-95-011 and through cooperative agreements with members of the Colon CFR and Principal Investigators. Collaborating centres include Australasian Colorectal Cancer Family Registry (U01 CA097735), the USC Familial Colorectal Neoplasia Collaborative Group (U01 CA074799), Mayo Clinic Cooperative Family Registry for Colon Cancer Studies (U01 CA074800), Ontario Registry for Studies of Familial Colorectal Cancer (U01 CA074783), Seattle Colorectal Cancer Family Registry (U01 CA074794) and University of Hawaii Colorectal Cancer Family Registry (U01 CA074806). This work was also supported by a grant from NHMRC Australia (ID 400160). The content of this manuscript neither necessarily reflect the views or policies of the National Cancer Institute or any of the collaborating centres in the CFRs, nor does mention of trade names, commercial products or organisations implies endorsement by the US Government or the CFR. We had full responsibility for the design of the study, the collection of the data, the analysis",

year = "2011",

month = jun,

day = "28",

doi = "10.1038/bjc.2011.172",

language = "English (US)",

volume = "105",

pages = "162--169",

journal = "British Journal of Cancer",

issn = "0007-0920",

publisher = "Nature Publishing Group",

number = "1",

}

TY - JOUR

T1 - Body mass index in early adulthood and colorectal cancer risk for carriers and non-carriers of germline mutations in DNA mismatch repair genes

AU - Win, A. K.

AU - Dowty, J. G.

AU - English, D. R.

AU - Campbell, P. T.

AU - Young, J. P.

AU - Winship, I.

AU - MacRae, F. A.

AU - Lipton, L.

AU - Parry, S.

AU - Young, G. P.

AU - Buchanan, D. D.

AU - Martínez, M. E.

AU - Jacobs, E. T.

AU - Ahnen, D. J.

AU - Haile, R. W.

AU - Casey, G.

AU - Baron, J. A.

AU - Lindor, N. M.

AU - Thibodeau, S. N.

AU - Newcomb, P. A.

AU - Potter, J. D.

AU - Le Marchand, L.

AU - Gallinger, S.

AU - Hopper, J. L.

AU - Jenkins, M. A.

N1 - Funding Information: This work was supported by the National Cancer Institute, National Institutes of Health under RFA #CA-95-011 and through cooperative agreements with members of the Colon CFR and Principal Investigators. Collaborating centres include Australasian Colorectal Cancer Family Registry (U01 CA097735), the USC Familial Colorectal Neoplasia Collaborative Group (U01 CA074799), Mayo Clinic Cooperative Family Registry for Colon Cancer Studies (U01 CA074800), Ontario Registry for Studies of Familial Colorectal Cancer (U01 CA074783), Seattle Colorectal Cancer Family Registry (U01 CA074794) and University of Hawaii Colorectal Cancer Family Registry (U01 CA074806). This work was also supported by a grant from NHMRC Australia (ID 400160). The content of this manuscript neither necessarily reflect the views or policies of the National Cancer Institute or any of the collaborating centres in the CFRs, nor does mention of trade names, commercial products or organisations implies endorsement by the US Government or the CFR. We had full responsibility for the design of the study, the collection of the data, the analysis

PY - 2011/6/28

Y1 - 2011/6/28

N2 - Background:Carriers of germline mutations in DNA mismatch repair (MMR) genes have a high risk of colorectal cancer (CRC), but the modifiers of this risk are not well established. We estimated an association between body mass index (BMI) in early adulthood and subsequent risk of CRC for carriers and, as a comparison, estimated the association for non-carriers.Methods:A weighted Cox regression was used to analyse height and weight at 20 years reported by 1324 carriers of MMR gene mutations (500 MLH1, 648 MSH2, 117 MSH6 and 59 PMS2) and 1219 non-carriers from the Colon Cancer Family Registry.Results:During 122 304 person-years of observation, we observed diagnoses of CRC for 659 carriers (50%) and 36 non-carriers (3%). For carriers, the risk of CRC increased by 30% for each 5 kg m-2 increment in BMI in early adulthood (hazard ratio, HR: 1.30; 95% confidence interval, CI: 1.08-1.58; P0.01), and increased by 64% for non-carriers (HR: 1.64; 95% CI: 1.02-2.64; P0.04) after adjusting for sex, country, cigarette smoking and alcohol drinking (and the MMR gene that was mutated in carriers). The difference in HRs for carriers and non-carriers was not statistically significant (P0.50). For MLH1 and PMS2 (MutLα heterodimer) mutation carriers combined, the corresponding increase was 36% (HR: 1.36; 95% CI: 1.05-1.76; P0.02). For MSH2 and MSH6 (MutSα heterodimer) mutation carriers combined, the HR was 1.26 (95% CI: 0.96-1.65; P0.09). There was no significant difference between the HRs for MutLα and MutSα heterodimer carriers (P0.56).Conclusion:Body mass index in early adulthood is positively associated with risk of CRC for MMR gene mutation carriers and non-carriers.

AB - Background:Carriers of germline mutations in DNA mismatch repair (MMR) genes have a high risk of colorectal cancer (CRC), but the modifiers of this risk are not well established. We estimated an association between body mass index (BMI) in early adulthood and subsequent risk of CRC for carriers and, as a comparison, estimated the association for non-carriers.Methods:A weighted Cox regression was used to analyse height and weight at 20 years reported by 1324 carriers of MMR gene mutations (500 MLH1, 648 MSH2, 117 MSH6 and 59 PMS2) and 1219 non-carriers from the Colon Cancer Family Registry.Results:During 122 304 person-years of observation, we observed diagnoses of CRC for 659 carriers (50%) and 36 non-carriers (3%). For carriers, the risk of CRC increased by 30% for each 5 kg m-2 increment in BMI in early adulthood (hazard ratio, HR: 1.30; 95% confidence interval, CI: 1.08-1.58; P0.01), and increased by 64% for non-carriers (HR: 1.64; 95% CI: 1.02-2.64; P0.04) after adjusting for sex, country, cigarette smoking and alcohol drinking (and the MMR gene that was mutated in carriers). The difference in HRs for carriers and non-carriers was not statistically significant (P0.50). For MLH1 and PMS2 (MutLα heterodimer) mutation carriers combined, the corresponding increase was 36% (HR: 1.36; 95% CI: 1.05-1.76; P0.02). For MSH2 and MSH6 (MutSα heterodimer) mutation carriers combined, the HR was 1.26 (95% CI: 0.96-1.65; P0.09). There was no significant difference between the HRs for MutLα and MutSα heterodimer carriers (P0.56).Conclusion:Body mass index in early adulthood is positively associated with risk of CRC for MMR gene mutation carriers and non-carriers.

KW - body mass index

KW - colorectal cancer

KW - mismatch repair gene

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DO - 10.1038/bjc.2011.172

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Body mass index in early adulthood and colorectal cancer risk for carriers and non-carriers of germline mutations in DNA mismatch repair genes

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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