Strong Signature of Natural Selection within an FHIT Intron Implicated in Prostate Cancer Risk

Ding, Yan; Larson, Garrett P.; Rivas, Guillermo; Lundberg, Cathryn; Geller, Louis; Ouyang, Ching; Weitzel, Jeffrey N.; Archambeau, John O.; Slater, James B.; Daly, Mary B.; Benson, Al B.; Kirkwood, John M.; O’Dwyer, Peter J.; Sutphen, Rebecca; Stewart, James A.; Johnson, David H.; Nordborg, Magnus; Krontiris, Theodore G.

doi:10.1371/journal.pone.0003533

Cited by 12 publications

(9 citation statements)

References 44 publications

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“…Multiple SNPs in sequences under evolutionary constraint within FHIT intron 5 defined haplotypes with an increased risk of prostate cancer in European‐Americans. The results strongly support the involvement of the FHIT intronic region in an increased risk of prostate cancer [Ding et al, 2008].…”

Section: The Gene and Epigenesupporting

confidence: 82%

Pathology and biology associated with the fragile FHIT gene and gene product

Saldivar¹,

Shibata²,

Huebner³

2010

J of Cellular Biochemistry

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More than 12 years and >800 scientific publications after the discovery of the first gene at a chromosome fragile site, the FHIT gene at FRA3B, there are still questions to pursue concerning the selective advantage conferred to cells by loss of expression of FHIT, the most frequent target of allele deletion in precancerous lesions and cancers. These questions are considered in light of recent investigations of genetic and epigenetic alterations to the locus and in a retrospective consideration of biological roles of the Fhit protein discovered through functional studies.

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Section: The Gene and Epigenesupporting

confidence: 82%

Pathology and biology associated with the fragile FHIT gene and gene product

Saldivar¹,

Shibata²,

Huebner³

2010

J of Cellular Biochemistry

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“…Fourteen of 15 tumors (93.3%) with MSI showed MSI in intron 4 or 5 of the FHIT gene in our study, suggesting that introns 4 and 5 are highly unstable. Ding et al [26] recently reported the involvement of the FHIT intronic region in an increased risk of prostate cancer.…”

Section: Discussionmentioning

confidence: 99%

Allelic imbalance and abnormal expression of FHIT in endemic nasopharyngeal carcinoma: association with clinicopathological features

Deng

Zhou

2010

Eur Arch Otorhinolaryngol

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The FHIT gene is involved in the pathogenesis of many cancers. The aim of this study was to investigate allelic imbalance (AI) pattern at FHIT locus and alteration of FHIT gene in nasopharyngeal carcinoma (NPC) and analyzed potential correlation between AI, FHIT mRNA expression and clinicopathological factors. We examined AI, including loss of heterozygosity (LOH) and microsatellite instability (MSI), at FHIT locus in 41 cases of NPC by microsatellite analysis and FHIT gene status in 30 cases of NPC by nested reverse transcriptase-polymerase chain reaction and DNA sequencing. The frequencies of LOH and MSI at FHIT locus in NPC were 70.7% (29/41) and 36.6% (15/41), respectively. Thirteen of thirty (43.3%) NPCs exhibited aberrant FHIT transcripts. LOH and abnormal FHIT expression were correlated with advanced clinical stage and higher titers of immunoglobulin (Ig) A against Epstein-Barr virus capsid antigen (EBVCA-IgA) (p < 0.05). Abnormal FHIT expression was also correlated with tumor recurrence (p < 0.05). MSI was correlated with early clinical stage and higher titers of EBVCA-IgA (p < 0.05). AI at FHIT locus is a common event and contributes to genetic imbalance in NPC. The abnormalities of FHIT, presumably associated with genetic imbalance at FHIT locus, might be involved in the development and the tumor recurrence of NPC.

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“…This all becomes more important for specific findings, such as the strong signal of selection at the FHIT locus that predisposes to prostate cancer [112]. …”

Section: From Evolutionary Medicine To Evolutionary Molecular Medicinementioning

confidence: 99%

Evolutionary molecular medicine

et al. 2012

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Evolution has long provided a foundation for population genetics, but many major advances in evolutionary biology from the 20th century are only now being applied in molecular medicine. They include the distinction between proximate and evolutionary explanations, kin selection, evolutionary models for cooperation, and new strategies for tracing phylogenies and identifying signals of selection. Recent advances in genomics are further transforming evolutionary biology and creating yet more opportunities for progress at the interface of evolution with genetics, medicine, and public health. This article reviews 15 evolutionary principles and their applications in molecular medicine in hopes that readers will use them and others to speed the development of evolutionary molecular medicine.

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Strong Signature of Natural Selection within an FHIT Intron Implicated in Prostate Cancer Risk

Cited by 12 publications

References 44 publications

Pathology and biology associated with the fragile FHIT gene and gene product

Pathology and biology associated with the fragile FHIT gene and gene product

Allelic imbalance and abnormal expression of FHIT in endemic nasopharyngeal carcinoma: association with clinicopathological features

Evolutionary molecular medicine

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