Expression analysis onto microarrays of randomly selected cDNA clones highlights HOXB13 as a marker of human prostate cancer
BRITISH JOURNAL OF CANCER
Authors: Edwards, S; Campbell, C; Flohr, P; Shipley, J; Giddings, I; te-Poele, R; Dodson, A; Foster, C; Clark, J; Jhavar, S; Kovacs, G; Cooper, CS
Abstract
In a strategy aimed at identifying novel markers of human prostate cancer, we performed expression analysis using microarrays of clones randomly selected from a cDNA library prepared from the LNCaP prostate cancer cell line. Comparisons of expression profiles in primary human prostate cancer, adjacent normal prostate tissue, and a selection of other (nonprostate) normal human tissues, led to the identification of a set of clones that were judged as the best candidate markers of normal and/or malignant prostate tissue. DNA sequencing of the selected clones revealed that they included 10 genes that had previously been established as prostate markers: NKX3.1, KLK2, KLK3 (PSA), FOLH1 ( PSMA), STEAP2, PSGR, PRAC, RDH11, Prostein and FASN. Following analysis of the expression patterns of all selected and sequenced genes through interrogation of SAGE databases, a further three genes from our clone set, HOXB13, SPON2 and NCAM2, emerged as additional candidate markers of human prostate cancer. Quantitative RT-PCR demonstrated the specificity of expression of HOXB13 in prostate tissue and revealed its ubiquitous expression in a series of 37 primary prostate cancers and 20 normal prostates. These results demonstrate the utility of this expression-microarray approach in hunting for new markers of individual human cancer types.
The reduced folate carrier (RFC1) 80G > A and folate hydrolase 1 (FOLH1) 1561C > T polymorphisms and the risk of colorectal cancer: A nested case-referent study
SCANDINAVIAN JOURNAL OF CLINICAL & LABORATORY INVESTIGATION
Authors: Eklof, V.; Van Guelpen, B.; Hultdin, J.; Johansson, I.; Hallmans, G.; Palmqvist, R.
Abstract
Objective. Polymorphisms in genes involved in folate uptake and metabolism may affect folate status and, thereby, the risk of cancer. In this nested case-referent study, we related two such polymorphisms, reduced folate carrier (RFC1) 80GwA and folate hydrolase 1 ( FOLH1) 1561CwT, to the risk of colorectal cancer, taking into account pre- diagnostic plasma folate and total homocysteine concentrations and the MTHFR 677CwT polymorphism, which were analysed in a previous study. Material and methods. Subjects were 220 cases and 414 matched referents from the population- based Northern Sweden Health and Disease Study. Results. The RFC1 80A- allele was associated with reduced plasma folate and elevated plasma total homocysteine concentrations, but the result was statistically significant only for folate. In contrast, the FOLH1 1561T- allele was associated with higher plasma folate and reduced plasma total homocysteine concentrations, and the result was statistically significant only for homocysteine. Neither polymorphism was related to the risk of colorectal cancer, either in univariate analysis or after adjusting for body mass index, current smoking, recreational and occupational physical activity and alcohol intake. Further adjustment for folate or homocysteine status or the MTHFR 677CwT polymorphism did not affect risk estimates. Subjects with the RFC1 80AA genotype in combination with low plasma folate concentrations or the MTHFR 677TT genotype had a reduced risk of colorectal cancer of borderline statistical significance. Conclusions. These findings suggest that although the RFC1 80GwA and FOLH1 1561CwT polymorphisms may influence folate status, they are not likely to have a major independent role in the development of colorectal cancer.