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

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...

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Published in:Diabetes research and clinical practice Vol. 103; no. 2; pp. 328 - 337
Main Authors: 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
Format: Journal Article
Language:English
Published: Ireland Elsevier Ireland Ltd 01-02-2014
Subjects:
Adult
Aged
Alleles
Asian Continental Ancestry Group - genetics
Cancer
Cancer prediction
China
Diabetes Mellitus, Type 2 - epidemiology
Diabetes Mellitus, Type 2 - genetics
Endocrinology & Metabolism
Epidemiology
Female
Genetic Predisposition to Disease
Genetics
Genome-Wide Association Study
Genotype
Humans
Incidence
Male
Middle Aged
Neoplasms - epidemiology
Neoplasms - genetics
Polymorphism, Single Nucleotide
Prospective Studies
Type 2 diabetes
China
Type 2 diabetes
Genetics
Epidemiology
Cancer prediction
Cancer
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Summary: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.
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ISSN:0168-8227
1872-8227
DOI:10.1016/j.diabres.2013.12.016