Familial adenomatous polyposis (FAP) is caused by germline mutations in the adenomatous polyposis coli (APC) gene. Two promoters, 1A and 1B, have been recognized in APC, and 1B is thought to have a minor role in the regulation of the gene. We have identified a novel deletion encompassing half of this promoter in the largest family (Family 1) of the Swedish Polyposis Registry. The mutation leads to an imbalance in allele-specific expression of APC, and transcription from promoter 1B was highly impaired in both normal colorectal mucosa and blood from mutation carriers. To establish the significance of promoter 1B in normal colorectal mucosa (from controls), expression levels of specific transcripts from each of the promoters, 1A and 1B, were examined, and the expression from 1B was significantly higher compared with 1A. Significant amounts of transcripts generated from promoter 1B were also determined in a panel of 20 various normal tissues examined. In FAP-related tumors, the APC germline mutation is proposed to dictate the second hit. Mutations leaving two or three out of seven 20-amino-acid repeats in the central domain of APC intact seem to be required for tumorigenesis. We examined adenomas from mutation carriers in Family 1 for second hits in the entire gene without any findings, however, loss of the residual expression of the deleterious allele was observed. Three major conclusions of significant importance in relation to the function of APC can be drawn from this study; (i) germline inactivation of promoter 1B is disease causing in FAP; (ii) expression of transcripts from promoter 1B is generated at considerable higher levels compared with 1A, demonstrating a hitherto unknown importance of 1B; (iii) adenoma formation in FAP, caused by impaired function of promoter 1B, does not require homozygous inactivation of APC allowing for alternative genetic models as basis for adenoma formation.

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Background Acceptability of the recommended screening procedure represents a crucial determinant of the impact of colorectal cancer (CRC) screening programmes. This study aims to explore how individuals in CRC screening experience the screening procedure. Methods Study participants (n = 44), aged 60–62 years, screened by faecal immunochemical test (FIT) and/or colonoscopy, were recruited from the Screening of Swedish Colons (SCREESCO) study. Data were collected through six focus group discussions and 20 individual telephone interviews and analyzed using qualitative content analysis. Results The analysis resulted in 30 subcategories together forming four categories describing individuals’ experiences of the CRC screening procedure: From no worries to bothering emotions; Varying logistical concerns; Being well treated, but inconsistently informed and involved and Expectations not matching reality. Some subcategories only applied to either FIT or colonoscopy screening, while others applied to both screening procedures. Conclusions Undergoing CRC screening by FIT or colonoscopy is an individual experience. Strategies to improve patient experiences may include using one-sample FITs and optimizing bowel preparation and scheduling of colonoscopies according to individual preferences. Ensuring that needs for emotional support are acknowledged, together with clear and adequate information delivered at right time are further important aspects to consider.