BACKGROUND: Genetics plays an important role in the susceptibility to sporadic colorectal cancer (CRC). In the last 10 years genome-wide association studies (GWAS) have identified over 40 independent low penetrance polymorphic variants. However, these loci only explain around 1‑4% of CRC heritability, highlighting the dire need of identifying novel risk loci. In this study, we focused our attention on the genetic variability of the TAS2R16 gene, encoding for one of the bitter taste receptors that selectively binds to salicin, a natural antipyretic that resembles aspirin. Given the importance of inflammation in CRC, we tested whether polymorphic variants in this gene could affect the risk of developing this neoplasia hypothesizing a role of TAS2R16 in modulating chronic inflammation within the gut. METHODS: We performed an association study using 6 tagging SNPs, (rs860170, rs978739, rs1357949, rs1525489, rs6466849, rs10268496) that cover all TAS2R16 genetic variability. The study was carried out on 1902 CRC cases and 1532 control individuals from four European countries. RESULTS: We did not find any statistically significant association between risk of developing CRC and selected SNPs. However, after stratification by histology (colon vs. rectum) we found that rs1525489 was associated with increased risk of rectal cancer with a (Ptrend of = 0.0071). CONCLUSIONS: Our data suggest that polymorphisms within TAS2R16 gene do not have a strong influence on colon cancer susceptibility, but a possible role in rectal cancer should be further evaluated in larger cohorts.

• Keywords
• Cancer risk, Colon cancer, Colorectal cancer, Genetic association study, Polymorphisms, Rectal cancer, TAS2R16, Taste receptors,
• MeSH
• Taste Receptors, Type 2 MeSH
• Genetic Predisposition to Disease * MeSH
• Genetic Association Studies MeSH
• Polymorphism, Single Nucleotide * MeSH
• Middle Aged MeSH
• Humans MeSH
• Rectal Neoplasms genetics   MeSH
• Colonic Neoplasms genetics   MeSH
• Receptors, G-Protein-Coupled genetics   MeSH
• Aged MeSH
• Case-Control Studies MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Geographicals
• Czech Republic MeSH
• Italy MeSH
• Lithuania MeSH
• Spain MeSH
• Names of Substances
• Taste Receptors, Type 2 MeSH
• Receptors, G-Protein-Coupled MeSH

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.

• MeSH
• Alleles MeSH
• Adult MeSH
• Genetic Predisposition to Disease * MeSH
• Genotype MeSH
• Colorectal Neoplasms diagnosis   genetics   MeSH
• Middle Aged MeSH
• Humans MeSH
• Models, Genetic MeSH
• ATP Binding Cassette Transporter, Subfamily B, Member 1 genetics   MeSH
• ATP Binding Cassette Transporter, Subfamily B MeSH
• Polymorphism, Genetic * MeSH
• Risk MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Case-Control Studies MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Geographicals
• Czech Republic MeSH
• Names of Substances
• ABCB1 protein, human MeSH Browser
• ATP Binding Cassette Transporter, Subfamily B, Member 1 MeSH
• ATP Binding Cassette Transporter, Subfamily B MeSH

BACKGROUND: Ghrelin, an endogenous ligand for the growth hormone secretagogue receptor (GHSR), has two major functions: the stimulation of the growth hormone production and the stimulation of food intake. Accumulating evidence also indicates a role of ghrelin in cancer development. METHODS: We conducted a case-control study to examine the association of common genetic variants in the genes coding for ghrelin (GHRL) and its receptor (GHSR) with colorectal cancer risk. Pairwise tagging was used to select the 11 polymorphisms included in the study. The selected polymorphisms were genotyped in 680 cases and 593 controls from the Czech Republic. RESULTS: We found two SNPs associated with lower risk of colorectal cancer, namely SNPs rs27647 and rs35683. We replicated the two hits, in additional 569 cases and 726 controls from Germany. CONCLUSION: A joint analysis of the two populations indicated that the T allele of rs27647 SNP exerted a protective borderline effect (Ptrend = 0.004).

• MeSH
• Alleles MeSH
• Child MeSH
• DNA, Neoplasm genetics   MeSH
• Adult MeSH
• Genetic Predisposition to Disease MeSH
• Ghrelin genetics   metabolism   MeSH
• Incidence MeSH
• Colorectal Neoplasms epidemiology   genetics   metabolism   MeSH
• Middle Aged MeSH
• Humans MeSH
• Adolescent MeSH
• Young Adult MeSH
• Polymorphism, Genetic * MeSH
• Receptors, Ghrelin genetics   metabolism   MeSH
• Retrospective Studies MeSH
• Risk Factors MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Check Tag
• Child MeSH
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Adolescent MeSH
• Young Adult MeSH
• Male MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Multicenter Study MeSH
• Research Support, Non-U.S. Gov't MeSH
• Comparative Study MeSH
• Geographicals
• Czech Republic epidemiology   MeSH
• Germany epidemiology   MeSH
• Names of Substances
• DNA, Neoplasm MeSH
• Ghrelin MeSH
• Receptors, Ghrelin MeSH