Prognostic factors and survival disparities in right-sided versus left-sided colon cancer.

Right-sided colon cancer (RCC) and left-sided colon cancer (LCC) differ in features and outcomes because of variations in embryology, epidemiology, pathology, and prognosis. This study sought to identify significant factors impacting patient survival through Bayesian modelling. Data was retrospectively analysed from a colorectal neoplasia database.

Phenotype correlations with pathogenic DNA variants in the gene.

-associated polyposis (MAP) is an autosomal recessive disorder where the inheritance of constitutional biallelic pathogenic variants predisposes a person to the development of adenomas and colorectal cancer (CRC). It is also associated with extracolonic and extraintestinal manifestations that may overlap with the phenotype of familial adenomatous polyposis (FAP). Currently, there are discrepancies in the literature regarding whether certain phenotypes are truly associated with MAP.

Genotype-phenotype correlation of BMPR1a disease causing variants in juvenile polyposis syndrome.

Background: Juvenile Polyposis Syndrome (JPS) is an autosomal dominant condition with hamartomatous polyps in the gastrointestinal tract, associated with an increased risk of gastrointestinal malignancy. Disease causing variants (DCVs) in BMPR1a or SMAD4 account for 45-60% of JPS cases, with BMPR1a DCVs accounting for 17-38% of JPS cases. Within those with either a BMPR1a or SMAD4 DCV, there is phenotypic variability in location of polyps, risk of malignancy and extra-intestinal manifestations with limited published reports of gene-phenotype association or genotype-phenotype correlation.

Genetic variant interpretation: a primer for clinicians.

Clinicians beyond specialist genetic services are now able to order tests to interrogate the genetic basis of disease. Behind every genetic report lies a significant body of work that draws on decades of collaboration between clinicians, researchers and database curators. Understanding these advances in genetic variant interpretation may allow practising clinicians to develop a more nuanced appreciation of the role genetic variant interpretation can play in the diagnosis and management of heritable disorders.

No Difference in Penetrance between Truncating and Missense/Aberrant Splicing Pathogenic Variants in and : A Prospective Lynch Syndrome Database Study.

Background: Lynch syndrome is the most common genetic predisposition for hereditary cancer. Carriers of pathogenic changes in mismatch repair (MMR) genes have an increased risk of developing colorectal (CRC), endometrial, ovarian, urinary tract, prostate, and other cancers, depending on which gene is malfunctioning. In Lynch syndrome, differences in cancer incidence (penetrance) according to the gene involved have led to the stratification of cancer surveillance.

Uptake of hysterectomy and bilateral salpingo-oophorectomy in carriers of pathogenic mismatch repair variants: a Prospective Lynch Syndrome Database report.

Purpose: This study aimed to report the uptake of hysterectomy and/or bilateral salpingo-oophorectomy (BSO) to prevent gynaecological cancers (risk-reducing surgery [RRS]) in carriers of pathogenic MMR (path_MMR) variants.

Methods: The Prospective Lynch Syndrome Database (PLSD) was used to investigate RRS by a cross-sectional study in 2292 female path_MMR carriers aged 30-69 years.

Results: Overall, 144, 79, and 517 carriers underwent risk-reducing hysterectomy, BSO, or both combined, respectively.

Evaluation of literature searching tools for curation of mismatch repair gene variants in hereditary colon cancer.

Pathogenic constitutional genomic variants in the mismatch repair (MMR) genes are the drivers of Lynch syndrome; optimal variant interpretation is required for the management of suspected and confirmed cases. The International Society for Hereditary Gastrointestinal Tumours (InSiGHT) provides expert classifications for MMR variants for the US National Human Genome Research Institute's (NHGRI) ClinGen initiative and interprets variants with discordant classifications and those of uncertain significance (VUSs). Given the onerous nature of extracting information related to variants, literature searching tools which harness artificial intelligence may aid in retrieving information to allow optimum variant classification.

Risk-reducing hysterectomy and bilateral salpingo-oophorectomy in female heterozygotes of pathogenic mismatch repair variants: a Prospective Lynch Syndrome Database report.

Purpose: To determine impact of risk-reducing hysterectomy and bilateral salpingo-oophorectomy (BSO) on gynecological cancer incidence and death in heterozygotes of pathogenic MMR (path_MMR) variants.

Methods: The Prospective Lynch Syndrome Database was used to investigate the effects of gynecological risk-reducing surgery (RRS) at different ages.

Results: Risk-reducing hysterectomy at 25 years of age prevents endometrial cancer before 50 years in 15%, 18%, 13%, and 0% of path_MLH1, path_MSH2, path_MSH6, and path_PMS2 heterozygotes and death in 2%, 2%, 1%, and 0%, respectively.

Risk-Reducing Gynecological Surgery in Lynch Syndrome: Results of an International Survey from the Prospective Lynch Syndrome Database.

Purpose: To survey risk-reducing hysterectomy and bilateral salpingo-oophorectomy (BSO) practice and advice regarding hormone replacement therapy (HRT) in women with Lynch syndrome.

Methods: We conducted a survey in 31 contributing centers from the Prospective Lynch Syndrome Database (PLSD), which incorporates 18 countries worldwide. The survey covered local policies for risk-reducing hysterectomy and BSO in Lynch syndrome, the timing when these measures are offered, the involvement of stakeholders and advice regarding HRT.

Correction: Cancer risks by gene, age, and gender in 6350 carriers of pathogenic mismatch repair variants: findings from the Prospective Lynch Syndrome Database.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Survival by colon cancer stage and screening interval in Lynch syndrome: a prospective Lynch syndrome database report.

Background: We previously reported that in pathogenic mismatch repair () variant carriers, the incidence of colorectal cancer (CRC) was not reduced when colonoscopy was undertaken more frequently than once every 3 years, and that CRC stage and interval since last colonoscopy were not correlated.

Methods: The Prospective Lynch Syndrome Database (PLSD) that records outcomes of surveillance was examined to determine survival after colon cancer in relation to the time since previous colonoscopy and pathological stage. Only variants scored by the InSiGHT variant database as class 4 or 5 (clinically actionable) were included in the analysis.

A snapshot of current genetic testing practice in Lynch syndrome: The results of a representative survey of 33 Latin American existing centres/registries.

We aimed to assess the current genetics practice to manage patients with Lynch syndrome (LS) across Latin America. A Latin American LS survey was sent out to 52 centres/registries, comprising a total of 12 countries from the region. Overall, 33 centres completed the survey, of which the oldest LS registry was established in 1992 in Sao Paulo (Brazil), and the youngest this year in San Jose (Costa Rica).

Lack of association between screening interval and cancer stage in Lynch syndrome may be accounted for by over-diagnosis; a prospective Lynch syndrome database report.

Background: Recent epidemiological evidence shows that colorectal cancer (CRC) continues to occur in carriers of pathogenic mismatch repair () variants despite frequent colonoscopy surveillance in expert centres. This observation conflicts with the paradigm that removal of all visible polyps should prevent the vast majority of CRC in carriers, provided the screening interval is sufficiently short and colonoscopic practice is optimal.

Methods: To inform the debate, we examined, in the Prospective Lynch Syndrome Database (PLSD), whether the time since last colonoscopy was associated with the pathological stage at which CRC was diagnosed during prospective surveillance.

From colorectal cancer pattern to the characterization of individuals at risk: Picture for genetic research in Latin America.

Colorectal cancer (CRC) is one of the most common cancers in Latin America and the Caribbean, with the highest rates reported for Uruguay, Brazil and Argentina. We provide a global snapshot of the CRC patterns, how screening is performed, and compared/contrasted to the genetic profile of Lynch syndrome (LS) in the region. From the literature, we find that only nine (20%) of the Latin America and the Caribbean countries have developed guidelines for early detection of CRC, and also with a low adherence.

Colorectal cancer incidence in carriers subjected to different follow-up protocols: a Prospective Lynch Syndrome Database report.

Background: We have previously reported a high incidence of colorectal cancer (CRC) in carriers of pathogenic variants ) despite follow-up with colonoscopy including polypectomy.

Methods: The cohort included Finnish carriers enrolled in 3-yearly colonoscopy ( = 505; 4625 observation years) and carriers from other countries enrolled in colonoscopy 2-yearly or more frequently ( = 439; 3299 observation years). We examined whether the longer interval between colonoscopies in Finland could explain the high incidence of CRC and whether disease expression correlated with differences in population CRC incidence.

An exploration of genotype-phenotype link between Peutz-Jeghers syndrome and STK11: a review.

Peutz-Jeghers Syndrome (PJS) is an autosomal dominant hereditary polyposis syndrome. Clinical features include hamartomatous polyps, mucocutaneous pigmentation and an increased predisposition towards developing malignancy. Variants in STK11, a tumour suppressor gene, located on Chromosome 19, predispose to PJS.

Cancer risk and survival in carriers by gene and gender up to 75 years of age: a report from the Prospective Lynch Syndrome Database.

Background: Most patients with gene variants (Lynch syndrome (LS)) now survive both their first and subsequent cancers, resulting in a growing number of older patients with LS for whom limited information exists with respect to cancer risk and survival.

Objective And Design: This observational, international, multicentre study aimed to determine prospectively observed incidences of cancers and survival in carriers up to 75 years of age.

Results: 3119 patients were followed for a total of 24 475 years.

Incidence of and survival after subsequent cancers in carriers of pathogenic MMR variants with previous cancer: a report from the prospective Lynch syndrome database.

Objective: Today most patients with Lynch syndrome (LS) survive their first cancer. There is limited information on the incidences and outcome of subsequent cancers. The present study addresses three questions: (i) what is the cumulative incidence of a subsequent cancer; (ii) in which organs do subsequent cancers occur; and (iii) what is the survival following these cancers?

Design: Information was collated on prospectively organised surveillance and prospectively observed outcomes in patients with LS who had cancer prior to inclusion and analysed by age, gender and genetic variants.

Harmonizing the interpretation of genetic variants across the world: the Malaysian experience.

Background: Databases for gene variants are very useful for sharing genetic data and to facilitate the understanding of the genetic basis of diseases. This report summarises the issues surrounding the development of the Malaysian Human Variome Project Country Node. The focus is on human germline variants.