E. Dietzsch

Lysyl oxidase-like 2 expression is increased in colon and esophageal tumors and associated with less differentiated colon tumors.

Lysyl oxidase‐like 2 (LOXL2) belongs to an amine oxidase family whose members have been implicated in crosslink formation in stromal collagens and elastin, cell motility, and tumor development and progression. We previously demonstrated the association between increased LOXL2 expression and invasive/metastatic behavior in human breast cancer cells and mouse squamous and spindle cell carcinomas, interaction between LOXL2 and SNAIL in epithelial‐mesenchymal transition, and localization of the LOXL2 gene to 8p21.2–21.3, within a minimally deleted region in several cancers, including colon and esophagus. In the present study, we analyzed LOXL2 expression in colon and esophageal tumors, and explored methylation as a regulator of LOXL2 expression. Immunohistochemistry using normal tissues demonstrated intracellular localization of LOXL2 in colonic enteroendocrine cells and esophageal squamous cells at the luminal surface, but not in mitotically active cells. Tissue array analysis of 52 colon adenocarcinomas and 50 esophageal squamous cell carcinomas revealed presence of LOXL2 expression in 83 and 92% of the samples, respectively, and a significant association between increased number of LOXL2‐expressing cells and less‐differentiated colon carcinomas. We determined that the methylation status of the 1150 bp 5′ CpG island may contribute to the regulation of the gene. Loss of heterozygosity studies, using a microsatellite within intron 4 of the LOXL2 gene, revealed that loss of LOXL2 was unlikely to play a major role in either colon or esophageal tumors. These results suggest that increased LOXL2 expression in colon and esophageal cancer may contribute to tumor progression.

Esophageal cancer risk in relation to GGC and CAG trinucleotide repeat lengths in the androgen receptor gene

The incidence of esophageal squamous cell cancer in African males in South Africa is one of the highest in the world. Because most patients present with advanced disease such that survival is poor, the identification of high‐risk individuals will facilitate early disease detection. Two polymorphic triplet repeats—(CAG)n and (GGC)n—in the androgen receptor gene were evaluated as potential genetic susceptibility loci for esophageal squamous cell cancer. Shorter lengths of these alleles have been reported to be associated with increased risk for prostate cancer. Our study sample comprised African males (29 patients and 109 controls), African females (14 patients and 59 controls) and Colored males (15 patients and 58 controls) whose alleles were analyzed singly and in combination. As in prostate cancer, the short (GGC)n alleles were implicated in esophageal cancer in African males: the average allele length was significantly shorter in patients compared to controls (p = 0.018), and a short (GGC)n allele was associated with elevated risk for disease [(GGC)≤16 odds ratio (OR) 2.7, 95% confidence interval (CI) 1.14–6.36; (GGC)≤14 OR 3.3, 95% CI 1.29–8.44]. There was no evidence, however, that short (CAG)n repeat alleles increased susceptibility to the disease. When the 2 alleles were considered jointly, additional information on predisposition was gained, revealing 2 haplotypes conferring a protective effect, i.e., [(CAG)>21 (GGC)≤16] OR 0.31, 95% CI 0.11–0.88; [(CAG)≤21 (GGC)>16] OR 0.26, 95% CI 0.11–0.65. Analysis using logistic regression led to narrower CIs for the ORs and enabled presentation of a risk profile.

EFFECT OF ROOPEROL ON COLLAGEN SYNTHESIS AND CELL GROWTH

The effect of rooperol on type I collagen synthesis in normal skin and lung fibroblasts and cell growth in normal and transformed fibroblasts was investigated. Low concentrations of rooperol selectively inhibited the growth of transformed cells while stimulating collagen synthesis in normal fibroblasts. Elevated collagen synthesis and deposition could impede tumour cell invasion and metastasis, implying that rooperol may be useful as an antimetastatic agent in the treatment of cancer.

CA repeat polymorphism in the promoter region of the COL1A2 gene

AbstractA polymorphic CA dinucleotide repeat sequence has been identified within the promoter of the human α2(I) procollagen gene, located at 7q21.3–q22.1. Nine alleles have been identified in unrelated individuals and the observed heterozygosity for the polymorphism was 0.66. This marker may be useful in the prenatal diagnosis of inherited connective tissue diseases in which the COL1A2 gene is involved. Furthermore, it may potentially improve the usefulness of the COL1A2 genetic system as an anthropogenetic marker.

Infrequent Somatic Deletion of the 5' Region of the COL1A2 Gene in Oesophageal Squamous Cell Cancer Patients

Abstract Oesophageal squamous cell cancer is the leading cause of cancer death amongst African males in South Africa. DNA was isolated from normal and tumour biopsies of the oesophagi of 33 African patients with squamous cell carcinoma of the oesophagus and was analysed with two dinucleotide repeat polymorphisms, a GT repeat sequence in the first intron, and a CA repeat in the promoter of the human α2(I) procollagen gene (COL1A2), using the polymerase chain reaction (PCR). Normal and tumour DNAs from each individual were compared to identify changes present in the tumour DNA, but absent in normal DNA. Twenty two cases were informative (heterozygous) for the promoter polymorphism and 24 cases were informative for the intronic polymorphism. Loss of heterozygosity (LOH) was seen in 2/22 (9.1%) for the promoter and 3/24 (12.5%) for the intronic polymorphism. These changes involved a total of three patients: two patients displayed the lost allele incorporating both the CA repeat and GT repeat loci; the third patient revealed LOH at the intronic polymorphism, but was non-informative (homozygous) for the promoter polymorphism. Deletions within the procollagen genes may represent an as yet unrecognised but rare event in the multistep process of carcinogenesis.