COL11A1 in FAP polyps and in sporadic colorectal tumors

BACKGROUND: We previously reported that the α-1 chain of type 11 collagen (COL11A1), not normally expressed in the colon, was up-regulated in stromal fibroblasts in most sporadic colorectal carcinomas. Patients with germline mutations in the APC gene show, besides colonic polyposis, symptoms of stromal fibroblast involvement, which could be related to COL11A1 expression. Most colorectal carcinomas are suggested to be a result of an activated Wnt- pathway, most often involving an inactivation of the APC gene or activation of β-catenin. METHODS: We used normal and polyp tissue samples from one FAP patient and a set of 37 sporadic colorectal carcinomas to find out if the up-regulation of COL11A1 was associated with an active APC/β-catenin pathway. RESULTS: In this study we found a statistically significant difference in COL11A1 expression between normal tissue and adenomas from one FAP patient, and all adenomas gave evidence for an active APC/β-catenin pathway. An active Wnt pathway has been suggested to involve stromal expression of WISP-1. We found a strong correlation between WISP-1 and COL11A1 expression in sporadic carcinomas. CONCLUSIONS: Our results suggest that expression of COL11A1 in colorectal tumors could be associated with the APC/β-catenin pathway in FAP and sporadic colorectal cancer

Heritable breast cancer in twins

Known major mutations such as BRCA1/2 and TP53 only cause a small proportion of heritable breast cancers. Co-dominant genes of lower penetrance that regulate hormones have been thought responsible for most others. Incident breast cancer cases in the identical (monozygotic) twins of representative cases reflect the entire range of pertinent alleles, whether acting singly or in combination. Having reported the rate in twins and other relatives of cases to be high and nearly constant over age, we now examine the descriptive and histological characteristics of the concordant and discordant breast cancers occurring in 2310 affected pairs of monozygotic and fraternal (dizygotic) twins in relation to conventional expectations and hypotheses. Like other first-degree relatives, dizygotic co-twins of breast cancer cases are at higher than usual risk (standardised incidence ratio (SIR)=1.7, CI=1.1–2.6), but the additional cases among monozygotic co-twins of cases are much more numerous, both before and after menopause (SIR=4.4, CI=3.6–5.6), than the 100% genetic identity would predict. Monozygotic co-twin diagnoses following early proband cancers also occur more rapidly than expected (within 5 years, SIR=20.0, CI=7.5–53.3). Cases in concordant pairs represent heritable disease and are significantly more likely to be oestrogen receptor-positive than those of comparable age from discordant pairs. The increase in risk to the monozygotic co-twins of cases cannot be attributed to the common environment, to factors that cumulate with age, or to any aggregate of single autosomal dominant mutations. The genotype more plausibly consists of multiple co-existing susceptibility alleles acting through heightened susceptibility to hormones and/or defective tumour suppression. The resultant class of disease accounts for a larger proportion of all breast cancers than previously thought, with a rather high overall penetrance. Some of the biological characteristics differ from those of breast cancer generally