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

A hypothesis-generating search for new genetic breast cancer syndromes - a national study in 803 Swedish families

Abstract Among Swedish families with an inherited predisposition for breast cancer, less than one third segregate mutations in genes known to be associated with an increased risk of breast cancer in combination with other types of tumours. In a search for new putative familial breast cancer syndromes we studied Swedish families undergoing genetic counselling during 1992-2000. Four thousand families from counselling clinics in Sweden were eligible for study. Families with breast cancer only were excluded, as were families with mutations in genes already known to be associated with malignant diseases. We identified 803 families with two or more cases of breast cancer and at least one other type of cancer. The observed proportion of different types of non-breast cancer was compared with the percentage distribution of non-breast cancer tumours in Sweden in 1958 and 1999. We found tumours in the colon, ovary, endometrium, pancreas and liver, as well as leukaemia in a significantly larger proportion of the study population than in the general population in both years. These tumours were also seen among families where several members had one additional tumour, suggesting that malignancies at these sites, in combination with breast tumours, could constitute genetic syndromes. Endometrial carcinoma has not previously been described in the context of breast cancer syndromes and the excess of malignancies at this site could not be explained by secondary tumours. Thus, we suggest that endometrial carcinoma and breast cancer constitute a new breast cancer syndrome. Further investigation is warranted to categorize phenotypes of both breast and endometrial tumours in this subgroup.</p

<it>COL11A1</it> in FAP polyps and in sporadic colorectal tumors

Abstract 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.</p

Complex segregation analysis of hypospadias

Hypospadias, when the urethra opens on the ventral side of the penis, is a common malformation seen in about 3 per 1000 male births. It is considered a complex disorder with both genetic and environmental factors involved in the pathogenesis. Low birth weight is known to be an important risk factor for hypospadias, but several observations speak in favour of genetic factors as well. In order to delineate the relative contribution of the genetic factors behind hypospadias, we performed a complex segregation analysis of 2005 pedigrees in Sweden. The probands were ascertained through the departments of paediatric surgery and departments of plastic surgery and urology in Sweden where boys with hypospadias undergo surgery. In 7% of the ascertained families one or more additional cases of hypospadias were present. The complex segregation analysis showed a heritability of 0.99 and evidence for multifactorial inheritance. The results suggest that hypospadias might be due to monogenic effects in a small proportion of the families, but that there is a multifactorial cause for the majority of the cases

A hypothesis-generating search for new genetic breast cancer syndromes - a national study in 803 Swedish families

Among Swedish families with an inherited predisposition for breast cancer, less than one third segregate mutations in genes known to be associated with an increased risk of breast cancer in combination with other types of tumours. In a search for new putative familial breast cancer syndromes we studied Swedish families undergoing genetic counselling during 1992-2000. Four thousand families from counselling clinics in Sweden were eligible for study. Families with breast cancer only were excluded, as were families with mutations in genes already known to be associated with malignant diseases. We identified 803 families with two or more cases of breast cancer and at least one other type of cancer. The observed proportion of different types of non-breast cancer was compared with the percentage distribution of non-breast cancer tumours in Sweden in 1958 and 1999. We found tumours in the colon, ovary, endometrium, pancreas and liver, as well as leukaemia in a significantly larger proportion of the study population than in the general population in both years. These tumours were also seen among families where several members had one additional tumour, suggesting that malignancies at these sites, in combination with breast tumours, could constitute genetic syndromes. Endometrial carcinoma has not previously been described in the context of breast cancer syndromes and the excess of malignancies at this site could not be explained by secondary tumours. Thus, we suggest that endometrial carcinoma and breast cancer constitute a new breast cancer syndrome. Further investigation is warranted to categorize phenotypes of both breast and endometrial tumours in this subgroup