We identified an endometrial cancer susceptibility locus close to HNF1B at 17q12 (rs4430796, P = 7.1 × 10(-10)) that is also associated with risk of prostate cancer and is inversely associated with risk of type 2 diabetes.
Besides, the haplotype-based analysis demonstrated that AGT in block rs752010-rs4430796-rs7501939 was associated with about 30% increase in T2D risk (OR 1.31, 95% CI 1.09-1.57, P = 0.01).
Where type 2 diabetes was the outcome, only one statistically significant interaction effect was observed, and this was for the HNF1B rs4430796 variant (P(interaction) = 0.0004).
Nominal interactions were observed for sleep duration and PPARG rs1801282, CRY2 rs7943320 and HNF1B rs4430796 in influencing risk of type 2 diabetes (p < 0.05).
The results of this study indicate that the use of 8 genetic polymorphisms associated with carbohydrate and lipid metabolism and type 2 diabetes [<i>PTGS2</i> (<i>COX2</i>) rs6681231, <i>FADS1</i> rs174550, <i>HNF1B</i> rs4430796, <i>ADIPOQ</i> rs266729, <i>IL18</i> rs187238, <i>CCL2</i> rs1024611, <i>HHEX</i> rs5015480 and <i>CDKN2A/2B</i> rs10811661] together with clinical risk factors (BMI and age) may significantly improve the prediction of GDM.
COL8A1 rs792837 (P=2.9 × 10(-9)), KCNQ1 rs2237892 (P=1.8 × 10(-18)) and rs2237895 (P=0.002), ALX4 rs729287 (Pc=7.5 × 10(-5)), and HNF1 rs4430796 (P=0.003) were significantly associated with T2DM, with similar effect sizes to those of Europeans.
Consistent with the initial study, we observed evidence that the risk G allele of rs4430796 in intron 2 was significantly associated with type 2 diabetes (odds ratio 1.16 [95% CI 1.05-1.29], P = 0.0035, empirical P = 0.0475).
The S465R mutation was found in 0.5% of our patients with common type 2 diabetes and thus may be a rare genetic risk factor contributing to the development of type 2 diabetes rather than MODY5.
Strong significant associations were found between rs4430796 A and the risk of both prostate cancer (OR = 1.247, p = 2.21 × 10<sup>- 77</sup>) and endometrial cancer (OR = 1.217, p = 8.98 × 10<sup>- 16</sup>); the AA, AG genotypes also showed strong significant associations with the risk of prostate cancer (OR1 = 1.517, p = 4.46 × 10<sup>- 22</sup>; OR2 = 1.180, p = 0.002).
Three HNF1B SNPS, rs11649743, rs4430796, and rs7501939, were associated with decreased risk of prostate cancer and were also associated, with marginal statistical significance, with increased risk of diabetes.
Three HNF1B SNPS, rs11649743, rs4430796, and rs7501939, were associated with decreased risk of prostate cancer and were also associated, with marginal statistical significance, with increased risk of diabetes.
Individuals with the rs4430796 TT genotype were at increased CaP risk in the Chinese via a recessive model (odds ratios (OR) = 1.56, 95% CI = 1.04-2.33).
We identified an endometrial cancer susceptibility locus close to HNF1B at 17q12 (rs4430796, P = 7.1 × 10(-10)) that is also associated with risk of prostate cancer and is inversely associated with risk of type 2 diabetes.
After subgroup analyses stratified by ethnicity, however, the rs4430796 polymorphism was significantly associated with prostate cancer in both Caucasians and Asians but not in African-Americans.
Notably, rs4430796 was significantly associated with prostate cancer among men diagnosed at an early (<50 years) but not later age (P = 0.006 versus P = 0.118).
Six markers associated with early-onset prostate cancer [rs2171492 (7q32), rs6983561 (8q24), rs10993994 (10q11), rs4430796 (17q12), rs1799950 (17q21), and rs266849 (19q13)] were genotyped.
After adjustments for age, the C allele of rs6983561 and the A allele of rs4430796 were significantly more frequent among the SPCa patients than among the controls.
Strong significant associations were found between rs4430796 A and the risk of both prostate cancer (OR = 1.247, p = 2.21 × 10<sup>- 77</sup>) and endometrial cancer (OR = 1.217, p = 8.98 × 10<sup>- 16</sup>); the AA, AG genotypes also showed strong significant associations with the risk of prostate cancer (OR1 = 1.517, p = 4.46 × 10<sup>- 22</sup>; OR2 = 1.180, p = 0.002).
Ten SNPs were significantly related to prostate cancer risk at a genome-wide significance level of P < 5 × 10(-8) with the most significant association with rs4430796 (P = 1.62 × 10(-24)).
Specifically, we sought to evaluate for effect modification between DM, a newly discovered prostate cancer susceptibility locus on chromosome 17q12 (single nucleotide polymorphism rs4430796) and prostate cancer features.
After adjustments for age, the C allele of rs6983561 and the A allele of rs4430796 were significantly more frequent among the SPCa patients than among the controls.
Six markers associated with early-onset prostate cancer [rs2171492 (7q32), rs6983561 (8q24), rs10993994 (10q11), rs4430796 (17q12), rs1799950 (17q21), and rs266849 (19q13)] were genotyped.