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
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Article info
Publication history
Published online: January 27, 2014
Accepted:
December 18,
2013
Received in revised form:
October 24,
2013
Received:
July 11,
2013
Identification
Copyright
© 2013 Elsevier Ireland Ltd. Published by Elsevier Inc. All rights reserved.
