Genetic variants for type 2 diabetes and new-onset cancer in Chinese with type 2 diabetes
| Autor: | Andrea O.Y. Luk, Janice S. K. Ho, Peter C.Y. Tong, Maggie C.Y. Ng, Ying Wang, C. C. Chow, Wing-Yee So, H.M. Lee, Juliana C.N. Chan, Vincent Kl Lam, Xilin Yang, Gang Xu, A.P.S. Kong, Claudia H. T. Tam, Ronald C.W. Ma |
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| Rok vydání: | 2014 |
| Předmět: |
Adult
Male Oncology China medicine.medical_specialty Genotype Endocrinology Diabetes and Metabolism Single-nucleotide polymorphism Type 2 diabetes Polymorphism Single Nucleotide Endocrinology Asian People Neoplasms Internal medicine Internal Medicine medicine Humans Genetic Predisposition to Disease Prospective Studies Prospective cohort study CDKAL1 Alleles Aged Genetics SLC30A8 biology business.industry Incidence Hazard ratio Cancer General Medicine Middle Aged medicine.disease Diabetes Mellitus Type 2 biology.protein Female business TCF7L2 Genome-Wide Association Study |
| Zdroj: | Diabetes Research and Clinical Practice. 103:328-337 |
| ISSN: | 0168-8227 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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