| 1. |
- Campa, Daniele, et al.
(författare)
-
A Comprehensive Investigation on Common Polymorphisms in the MDR1/ABCB1 Transporter Gene and Susceptibility to Colorectal Cancer
- 2012
-
Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 7:3
-
Tidskriftsartikel (refereegranskat)abstract
- ATP Binding Cassette B1 (ABCB1) is a transporter with a broad substrate specificity involved in the elimination of several carcinogens from the gut. Several polymorphic variants within the ABCB1 gene have been reported as modulators of ABCB1-mediated transport. We investigated the impact of ABCB1 genetic variants on colorectal cancer (CRC) risk. A hybrid tagging/functional approach was performed to select 28 single nucleotide polymorphisms (SNPs) that were genotyped in 1,321 Czech subjects, 699 CRC cases and 622 controls. In addition, six potentially functional SNPs were genotyped in 3,662 German subjects, 1,809 cases and 1,853 controls from the DACHS study. We found that three functional SNPs (rs1202168, rs1045642 and rs868755) were associated with CRC risk in the German population. Carriers of the rs1202168_T and rs868755_T alleles had an increased risk for CRC (P-trend = 0.016 and 0.029, respectively), while individuals bearing the rs1045642_C allele showed a decreased risk of CRC (P-trend = 0.022). We sought to replicate the most significant results in an independent case-control study of 3,803 subjects, 2,169 cases and 1,634 controls carried out in the North of Germany. None of the SNPs tested were significantly associated with CRC risk in the replication study. In conclusion, in this study of about 8,800 individuals we show that ABCB1 gene polymorphisms play at best a minor role in the susceptibility to CRC.
|
|
| 2. |
- Sainz, Juan, et al.
(författare)
-
Effect of Type 2 Diabetes Predisposing Genetic Variants on Colorectal Cancer Risk.
- 2012
-
Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 97:5, s. 845-851
-
Tidskriftsartikel (refereegranskat)abstract
- Background: The link between colorectal cancer (CRC) and type 2 diabetes mellitus (T2D) has been extensively studied. Although it is commonly accepted that T2D is a risk factor for CRC, the underlying mechanisms are still poorly understood. Research Design and Methods:Given that the genetic background contributes to both traits, it is conceivable that genetic variants associated with T2D may also influence the risk of CRC. We selected 26 T2D-related single-nucleotide polymorphisms (SNP) previously identified by genome-wide association studies and assessed their association with CRC and their interaction with known risk factors (gender, T2D, and body mass index) of CRC. Selected SNP were genotyped in 1798 CRC cases and 1810 controls from the population-based Darmkrebs: Chancen der Verhütung durch Screening (DACHS) study (Germany). Results:Patients carrying the TCF7L2_rs7903146_T allele had an increased risk of CRC (P(trend) = 0.02), whereas patients harboring the IL13_rs20541_T allele had a reduced risk (P(trend) = 0.02). A further analysis revealed gender-specific effects: the TCF7L2_rs7903146_T allele was associated with an increased risk of CRC in women (P(trend) = 0.003) but not in men (P(interaction) = 0.06); the LTA_rs1041981_A allele was associated with a decreased risk for CRC in women (P(trend) = 0.02), with an opposite effect in men (P(trend) = 0.05; P(interaction) = 0.002); the CDKAL1_rs7754840_C allele was associated with a decreased risk for CRC in men (P(trend) = 0.03), with no effect in women (P(interaction) = 0.03). The risk associated with the presence of T2D was modified both by IGF2BP2_rs4402960 and PPARγ_rs1801282 SNP (P(interaction) = 0.04 and 0.04, respectively). None of the findings were significant after correction for multiple comparisons. Conclusions:These findings suggest that T2D-related variants modify CRC risk independently and/or in an interactive manner according to the gender and the presence or absence of T2D.
|
|
| 3. |
- Sainz, Juan, et al.
(författare)
-
GWAS-Identified Common Variants for Obesity Are Not Associated with the Risk of Developing Colorectal Cancer
- 2014
-
Ingår i: Cancer Epidemiology Biomarkers & Prevention. - 1538-7755. ; 23:6, s. 1125-1128
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Observational studies have consistently associated obesity with colorectal cancer risk. Because both traits are genetically determined and share some metabolic biomarkers, we hypothesized that obesity-related polymorphisms could also influence the risk of developing colorectal cancer. Methods: We conducted a comprehensive population-based case-control study in 1,792 German colorectal cancer cases and 1,805 controls to explore associations between 28 obesogenic variants identified through genome-wide association studies (GWAS) and colorectal cancer risk. We also evaluated interactions between polymorphisms and body mass index (BMI), type II diabetes (T2D), and gender. Results: No evidence of association between obesogenic variants and colorectal cancer risk was observed after correction for multiple testing. There was only a remarkable interaction between the LTA(rs1041981) polymorphism and gender, which modified the risk of colorectal cancer [P-interaction - 0.002; males: odds ratio (OR), 1.14; 95% confidence intervals (CI), 1.00-1.30 vs. females: OR, 0.83; 95% CI, 0.71-0.97]. Conclusions: Our findings showed that obesogenic variants are not a major pathogenetic risk factor for colorectal cancer.
|
|
