Search PubMed⌕ Search
Home/Archive/PubMed

PubMed · 15256231

Candidate gene polymorphisms in solid cancers.

S P Balasubramanian·A Cox·N J Brown·M W Reed
View original source ↗Export metadata ↓

Abstract

Accumulation of information from scientific advances in genetics and biotechnology has accelerated research investigating the inherent individual variation in disease susceptibility and severity. Gene polymorphisms, in particular single nucleotide polymorphisms, are being evaluated for their role in multi-factorial diseases such as cancer and inflammation. Most surgical diseases are multi-factorial and a better understanding and utilization of the information gained from such studies by clinicians/surgeons is likely to favorably influence patient outcome. In this article, we illustrate the types of genetic variation and the complexities involved in their study and discuss their potential in predicting both the occurrence and outcomes of solid cancers.

Explore related subjects

Genetic Predisposition to DiseaseGenetic VariationHaplotypesHumansNeoplasmsOutcome Assessment, Health CarePolymorphism, GeneticSeverity of Illness IndexSurgical Procedures, OperativeJournal ArticleReview

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

S P Balasubramanian, A Cox, N J Brown, M W Reed. 2004. Candidate gene polymorphisms in solid cancers.. https://doi.org/10.1016/j.ejso.2004.04.001

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

PubMed2026

Phenotypic manifestations and variant reclassification of germline PTEN variants: a nationwide Danish study.

BACKGROUND: Classification of heterozygous germline PTEN variants in patients with, or suspected of having, PTEN hamartoma tumour syndrome (PHTS) remains challenging. Accurate classification is essential as these patients require lifelong cancer surveillance. METHODS: We identified all patients with a PTEN variant previously classified as a variant of uncertain significance (VUS), likely pathogenic (LP) or pathogenic (P), collected clinical data and reclassified all variants using the latest PTEN gene-specific American College of Medical Genetics (ACMG) guidelines. Moreover, genotype-phenotype correlations were assessed. RESULTS: 167 patients from 112 families were enrolled. Eighty-seven unique PTEN variants were identified, including 20 novel variants. After applying the PTEN gene-specific ACMG guidelines, 32 variants (36.8%) were reclassified, resulting in 60 PTEN variants classified as LP/P (69.0%), 18 variants classified as VUS (20.7%), while 9 variants were classified as LB/B (10.3%). Genotype-phenotype correlation was performed among 104 patients with LP/P variants: 51 cancer cases were recorded in 41 patients and a distinct PHTS phenotype was observed in 25% of patients, with macrocephaly being present in 99% of patients with a known head circumference. Twenty-three patients had neurodevelopmental delay and/or autism, and we observed an increased prevalence of missense variants in these patients. CONCLUSION: We identified 87 different PTEN variants, and application of PTEN gene-specific ACMG guidelines led to reclassification of 32 variants (36.8%), underscoring the importance of regular variant reassessment using the most recent gene-specific guidelines, ensuring optimal patient management and surveillance.

Genetic Predisposition to Disease↗
PubMed2014

Genetics and intelligence differences: five special findings.

Intelligence is a core construct in differential psychology and behavioural genetics, and should be so in cognitive neuroscience. It is one of the best predictors of important life outcomes such as education, occupation, mental and physical health and illness, and mortality. Intelligence is one of the most heritable behavioural traits. Here, we highlight five genetic findings that are special to intelligence differences and that have important implications for its genetic architecture and for gene-hunting expeditions. (i) The heritability of intelligence increases from about 20% in infancy to perhaps 80% in later adulthood. (ii) Intelligence captures genetic effects on diverse cognitive and learning abilities, which correlate phenotypically about 0.30 on average but correlate genetically about 0.60 or higher. (iii) Assortative mating is greater for intelligence (spouse correlations ~0.40) than for other behavioural traits such as personality and psychopathology (~0.10) or physical traits such as height and weight (~0.20). Assortative mating pumps additive genetic variance into the population every generation, contributing to the high narrow heritability (additive genetic variance) of intelligence. (iv) Unlike psychiatric disorders, intelligence is normally distributed with a positive end of exceptional performance that is a model for 'positive genetics'. (v) Intelligence is associated with education and social class and broadens the causal perspectives on how these three inter-correlated variables contribute to social mobility, and health, illness and mortality differences. These five findings arose primarily from twin studies. They are being confirmed by the first new quantitative genetic technique in a century-Genome-wide Complex Trait Analysis (GCTA)-which estimates genetic influence using genome-wide genotypes in large samples of unrelated individuals. Comparing GCTA results to the results of twin studies reveals important insights into the genetic architecture of intelligence that are relevant to attempts to narrow the 'missing heritability' gap.

Genetic Predisposition to Disease↗