Genetic variants for type 2 diabetes and new-onset cancer in Chinese with type 2 diabetes

R. C.W. Ma; W. Y. So; C. H.T. Tam; A. O. Luk; J. S.K. Ho; Y. Wang; V. K. Lam; H. M. Lee; A. P. Kong; P. C. Tong; Gang XU; C. C. Chow; M. C. Ng; X. L. Yang; J. C. Chan

doi:10.1016/j.diabres.2013.12.016

Genetic variants for type 2 diabetes and new-onset cancer in Chinese with type 2 diabetes

R. C.W. Ma^*, W. Y. So, C. H.T. Tam, A. O. Luk, J. S.K. Ho, Y. Wang, V. K. Lam, H. M. Lee, A. P. Kong, P. C. Tong, Gang XU, C. C. Chow, M. C. Ng, X. L. Yang, J. C. Chan

^*Corresponding author for this work

Research output: Contribution to journal › Journal article › peer-review

15 Citations (Scopus)

Abstract

Background: Diabetes is associated with an increased risk of cancer. This study aimed to evaluate associations between recently reported type 2 diabetes (T2D) susceptibility genetic variants and cancer risk in a prospective cohort of Chinese patients with T2D. Methods: Seven single nucleotide polymorphisms (SNP) in IGF2BP2, CDKAL1, SLC30A8, CDKN2A/B, HHEX and TCF7L2, all identified from genome-wide association studies of T2D, were genotyped in 5900 T2D patients [age mean. ±. SD=57. ±. 13 years, % males=46] without any known cancer at baseline. Associations between new-onset of cancer and SNPs were tested by Cox proportional hazard models with adjustment of conventional risk factors. Results: During the mean follow-up period of 8.5±3.3 years, 429 patients (7.3%) developed cancer. Of the T2D-related SNPs, the G-alleles of HHEX rs7923837 (hazard ratio [HR] (95% C.I.)=1.34 (1.08-1.65); P=6.7×10^-3 under dominant model) and TCF7L2 rs290481 (HR (95% C.I.)=1.16 (1.01-1.33); P=0.040 under additive model) were positively associated with cancer risk, while the G-allele of CDKAL1 rs7756992 was inversely associated (HR (95% C.I.)=0.80 (0.65-1.00); P=0.048 under recessive model). The risk alleles of these significant SNPs exhibited combined effect on increasing cancer risk (per-allele HR (95% C.I.)=1.25 (1.12-1.39); P=4.8×10^-5). The adjusted cancer risk was 2.41 (95% C.I. 1.23-4.69) for patients with four risk alleles comparing to patients without risk allele. Conclusions: T2D-related variants HHEX rs7923837, TCF7L2 rs290481 and CDKAL1 rs7756992 increased cancer risk in patients with diabetes. Impact: Our findings provide novel insights into the pathogenesis of cancer in diabetes.

Original language	English
Pages (from-to)	328-337
Number of pages	10
Journal	Diabetes Research and Clinical Practice
Volume	103
Issue number	2
DOIs	https://doi.org/10.1016/j.diabres.2013.12.016
Publication status	Published - Feb 2014

Scopus Subject Areas

Internal Medicine
Endocrinology, Diabetes and Metabolism
Endocrinology

User-Defined Keywords

Cancer
Cancer prediction
Epidemiology
Genetics
Type 2 diabetes

UN SDGs

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

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10.1016/j.diabres.2013.12.016

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Ma, R. C. W., So, W. Y., Tam, C. H. T., Luk, A. O., Ho, J. S. K., Wang, Y., Lam, V. K., Lee, H. M., Kong, A. P., Tong, P. C., XU, G., Chow, C. C., Ng, M. C., Yang, X. L., & Chan, J. C. (2014). Genetic variants for type 2 diabetes and new-onset cancer in Chinese with type 2 diabetes. Diabetes Research and Clinical Practice, 103(2), 328-337. https://doi.org/10.1016/j.diabres.2013.12.016

@article{cc0d32cc87b145edb9c2fe65d2083637,

title = "Genetic variants for type 2 diabetes and new-onset cancer in Chinese with type 2 diabetes",

abstract = "Background: Diabetes is associated with an increased risk of cancer. This study aimed to evaluate associations between recently reported type 2 diabetes (T2D) susceptibility genetic variants and cancer risk in a prospective cohort of Chinese patients with T2D. Methods: Seven single nucleotide polymorphisms (SNP) in IGF2BP2, CDKAL1, SLC30A8, CDKN2A/B, HHEX and TCF7L2, all identified from genome-wide association studies of T2D, were genotyped in 5900 T2D patients [age mean. ±. SD=57. ±. 13 years, % males=46] without any known cancer at baseline. Associations between new-onset of cancer and SNPs were tested by Cox proportional hazard models with adjustment of conventional risk factors. Results: During the mean follow-up period of 8.5±3.3 years, 429 patients (7.3%) developed cancer. Of the T2D-related SNPs, the G-alleles of HHEX rs7923837 (hazard ratio [HR] (95% C.I.)=1.34 (1.08-1.65); P=6.7×10-3 under dominant model) and TCF7L2 rs290481 (HR (95% C.I.)=1.16 (1.01-1.33); P=0.040 under additive model) were positively associated with cancer risk, while the G-allele of CDKAL1 rs7756992 was inversely associated (HR (95% C.I.)=0.80 (0.65-1.00); P=0.048 under recessive model). The risk alleles of these significant SNPs exhibited combined effect on increasing cancer risk (per-allele HR (95% C.I.)=1.25 (1.12-1.39); P=4.8×10-5). The adjusted cancer risk was 2.41 (95% C.I. 1.23-4.69) for patients with four risk alleles comparing to patients without risk allele. Conclusions: T2D-related variants HHEX rs7923837, TCF7L2 rs290481 and CDKAL1 rs7756992 increased cancer risk in patients with diabetes. Impact: Our findings provide novel insights into the pathogenesis of cancer in diabetes.",

keywords = "Cancer, Cancer prediction, Epidemiology, Genetics, Type 2 diabetes",

author = "Ma, {R. C.W.} and So, {W. Y.} and Tam, {C. H.T.} and Luk, {A. O.} and Ho, {J. S.K.} and Y. Wang and Lam, {V. K.} and Lee, {H. M.} and Kong, {A. P.} and Tong, {P. C.} and Gang XU and Chow, {C. C.} and Ng, {M. C.} and Yang, {X. L.} and Chan, {J. C.}",

note = "Funding Information: We thank all medical and nursing staff of the Prince of Wales Hospital Diabetes Centre for their commitment and professionalism. We would like to thank deCODE Genetics and the Genome Institution at Quebec for help with genotyping. We thank the Chinese University of Hong Kong Information Technology Services Centre for support of computing resources. Funding Information: The project was supported by the Hong Kong Foundation for Research and Development in Diabetes established under the auspices of the Chinese University of Hong Kong, the Hong Kong Government Research Grant Committee (Central allocation), the Innovation and Technology Fund (ITS/487/09FP), the Research Fund of the Department of Medicine and Therapeutics and the Diabetes and Endocrine Research Fund of the Chinese University of Hong Kong . The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. ",

year = "2014",

month = feb,

doi = "10.1016/j.diabres.2013.12.016",

language = "English",

volume = "103",

pages = "328--337",

journal = "Diabetes Research and Clinical Practice",

issn = "0168-8227",

publisher = "Elsevier Ireland Ltd",

number = "2",

}

TY - JOUR

T1 - Genetic variants for type 2 diabetes and new-onset cancer in Chinese with type 2 diabetes

AU - Ma, R. C.W.

AU - So, W. Y.

AU - Tam, C. H.T.

AU - Luk, A. O.

AU - Ho, J. S.K.

AU - Wang, Y.

AU - Lam, V. K.

AU - Lee, H. M.

AU - Kong, A. P.

AU - Tong, P. C.

AU - XU, Gang

AU - Chow, C. C.

AU - Ng, M. C.

AU - Yang, X. L.

AU - Chan, J. C.

N1 - Funding Information: We thank all medical and nursing staff of the Prince of Wales Hospital Diabetes Centre for their commitment and professionalism. We would like to thank deCODE Genetics and the Genome Institution at Quebec for help with genotyping. We thank the Chinese University of Hong Kong Information Technology Services Centre for support of computing resources. Funding Information: The project was supported by the Hong Kong Foundation for Research and Development in Diabetes established under the auspices of the Chinese University of Hong Kong, the Hong Kong Government Research Grant Committee (Central allocation), the Innovation and Technology Fund (ITS/487/09FP), the Research Fund of the Department of Medicine and Therapeutics and the Diabetes and Endocrine Research Fund of the Chinese University of Hong Kong . The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

PY - 2014/2

Y1 - 2014/2

N2 - Background: Diabetes is associated with an increased risk of cancer. This study aimed to evaluate associations between recently reported type 2 diabetes (T2D) susceptibility genetic variants and cancer risk in a prospective cohort of Chinese patients with T2D. Methods: Seven single nucleotide polymorphisms (SNP) in IGF2BP2, CDKAL1, SLC30A8, CDKN2A/B, HHEX and TCF7L2, all identified from genome-wide association studies of T2D, were genotyped in 5900 T2D patients [age mean. ±. SD=57. ±. 13 years, % males=46] without any known cancer at baseline. Associations between new-onset of cancer and SNPs were tested by Cox proportional hazard models with adjustment of conventional risk factors. Results: During the mean follow-up period of 8.5±3.3 years, 429 patients (7.3%) developed cancer. Of the T2D-related SNPs, the G-alleles of HHEX rs7923837 (hazard ratio [HR] (95% C.I.)=1.34 (1.08-1.65); P=6.7×10-3 under dominant model) and TCF7L2 rs290481 (HR (95% C.I.)=1.16 (1.01-1.33); P=0.040 under additive model) were positively associated with cancer risk, while the G-allele of CDKAL1 rs7756992 was inversely associated (HR (95% C.I.)=0.80 (0.65-1.00); P=0.048 under recessive model). The risk alleles of these significant SNPs exhibited combined effect on increasing cancer risk (per-allele HR (95% C.I.)=1.25 (1.12-1.39); P=4.8×10-5). The adjusted cancer risk was 2.41 (95% C.I. 1.23-4.69) for patients with four risk alleles comparing to patients without risk allele. Conclusions: T2D-related variants HHEX rs7923837, TCF7L2 rs290481 and CDKAL1 rs7756992 increased cancer risk in patients with diabetes. Impact: Our findings provide novel insights into the pathogenesis of cancer in diabetes.

AB - Background: Diabetes is associated with an increased risk of cancer. This study aimed to evaluate associations between recently reported type 2 diabetes (T2D) susceptibility genetic variants and cancer risk in a prospective cohort of Chinese patients with T2D. Methods: Seven single nucleotide polymorphisms (SNP) in IGF2BP2, CDKAL1, SLC30A8, CDKN2A/B, HHEX and TCF7L2, all identified from genome-wide association studies of T2D, were genotyped in 5900 T2D patients [age mean. ±. SD=57. ±. 13 years, % males=46] without any known cancer at baseline. Associations between new-onset of cancer and SNPs were tested by Cox proportional hazard models with adjustment of conventional risk factors. Results: During the mean follow-up period of 8.5±3.3 years, 429 patients (7.3%) developed cancer. Of the T2D-related SNPs, the G-alleles of HHEX rs7923837 (hazard ratio [HR] (95% C.I.)=1.34 (1.08-1.65); P=6.7×10-3 under dominant model) and TCF7L2 rs290481 (HR (95% C.I.)=1.16 (1.01-1.33); P=0.040 under additive model) were positively associated with cancer risk, while the G-allele of CDKAL1 rs7756992 was inversely associated (HR (95% C.I.)=0.80 (0.65-1.00); P=0.048 under recessive model). The risk alleles of these significant SNPs exhibited combined effect on increasing cancer risk (per-allele HR (95% C.I.)=1.25 (1.12-1.39); P=4.8×10-5). The adjusted cancer risk was 2.41 (95% C.I. 1.23-4.69) for patients with four risk alleles comparing to patients without risk allele. Conclusions: T2D-related variants HHEX rs7923837, TCF7L2 rs290481 and CDKAL1 rs7756992 increased cancer risk in patients with diabetes. Impact: Our findings provide novel insights into the pathogenesis of cancer in diabetes.

KW - Cancer

KW - Cancer prediction

KW - Epidemiology

KW - Genetics

KW - Type 2 diabetes

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DO - 10.1016/j.diabres.2013.12.016

M3 - Journal article

C2 - 24468095

AN - SCOPUS:84895789380

SN - 0168-8227

VL - 103

SP - 328

EP - 337

JO - Diabetes Research and Clinical Practice

JF - Diabetes Research and Clinical Practice

IS - 2

ER -

Genetic variants for type 2 diabetes and new-onset cancer in Chinese with type 2 diabetes

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