Cristina Álvarez-Urturi

BMPR1A mutations in early-onset colorectal cancer with mismatch repair proficiency

To the Editor : Germline alterations in the bone morphogenetic protein receptor type-1A (BMPR1A) gene have been recently related to colorectal cancer (CRC) development in patients with familial colorectal cancer type X (FCCX) (1). Moreover, they account for 20% and 50% of the juvenile polyposis (JP; OMIM #174900) and hereditary mixed polyposis syndrome (HMPS; OMIM #610069) cases, respectively. However, there have been no reports so far of its relationship with earlyonset (<50 years) CRC cases with no mismatch-repair (MMR) deficiency, no previous polyposis and no family history of CRC. In this work, we performed a rare copy-numbervariant (CNV) search in a set of 32 patients, who fulfilled the above-mentioned clinical features, to find any new high-penetrance genes related to CRC development. We found an early-onset CRC patient presented with a 7.326-Mb heterozygous deletion in the 10q22q23 region involving the BMPR1A gene. The study was approved by the ‘Comité Ético de Investigación Clínica de Galicia’, and the institutional review board of the hospital of origin of the patient. The samples were obtained with written informed consent in accordance with the tenets of the Declaration of Helsinki. Rare CNVs were screened for with the Affymetrix 6.0 array and selected by removing those detected in our in-house control CNV database (629 controls). Copynumber status was inferred with two algorithms (2, 3). The patient carrying the 10q22-q23 deletion is a male who displays two synchronous adenocarcinomas (onset age 49 years): pT3pN1 in the ascending colon and pT2pN1 in the rectum. Both tumours exhibited Lynch-compatible histology and immunohistochemical

Genetic Variants Associated with Colorectal Adenoma Susceptibility

Background Common low-penetrance genetic variants have been consistently associated with colorectal cancer risk. Aim To determine if these genetic variants are associated also with adenoma susceptibility and may improve selection of patients with increased risk for advanced adenomas and/or multiplicity (≥ 3 adenomas). Methods We selected 1,326 patients with increased risk for advanced adenomas and/or multiplicity and 1,252 controls with normal colonoscopy from population-based colorectal cancer screening programs. We conducted a case-control association study analyzing 30 colorectal cancer susceptibility variants in order to investigate the contribution of these variants to the development of subsequent advanced neoplasia and/or multiplicity. Results We found that 14 of the analyzed genetic variants showed a statistically significant association with advanced adenomas and/or multiplicity: the probability of developing these lesions increased with the number of risk alleles reaching a 2.3-fold risk increment in individuals with ≥ 17 risk alleles. Conclusions Nearly half of the genetic variants associated with colorectal cancer risk are also related to advanced adenoma and/or multiplicity predisposition. Assessing the number of risk alleles in individuals within colorectal cancer screening programs may help to identify better a subgroup with increased risk for advanced neoplasia and/or multiplicity in the general population.

Accuracy of Colon Capsule Endoscopy in Detecting Colorectal Polyps in Individuals with Familial Colorectal Cancer: Could We Avoid Colonoscopies?

Background. Individuals with a family history of colorectal cancer (CRC) have an increased risk of CRC. We evaluated the diagnostic yield of CCE in the detection of lesions and also two different colon preparations. Methods. A prospective multicenter study was designed to assess CCE diagnostic yield in a cohort of asymptomatic individuals with a family history of CRC. CCE and colonoscopy were performed on the same day by 2 endoscopists who were blinded to the results of the other procedure. Results. Fifty-three participants were enrolled. The sensitivity, specificity, PPV, and NPV of CCE for detecting advanced adenomas were 100%, 98%, 67%, and 100%. Sensitivity, specificity, PPV, and NPV of CCE for the diagnosis of individuals with polyps were 87%, 97%, 93%, and 88%, respectively. CCE identify 100% of individuals with significant or advanced lesions. Overall cleanliness was adequate by 60.7% of them. The PEG-ascorbic boost seems to improve colon cleanliness, with similar colonic transit time. Conclusion. CCE is a promising tool, but it has to be considered as an alternative technique in this population in order to reduce the number of colonoscopies performed. More studies are needed to understand appropriate screening follow-up intervals and optimize the bowel preparation regimen.