Fragile Sites in Chromosomes: Possible Model for the Study of Spontaneous Chromosome Breakage

Jacky, Peter B.; Beek, Bernd; Sutherland, Grant R.

doi:10.1126/science.6828880

Cited by 65 publications

(14 citation statements)

References 11 publications

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“…Consequently, imbalance of the dNTP pools can promote chromosome rearrangement, breakage and loss. [96][97][98] DNA mutations may activate proto-oncogenes and/or inactivate tumor suppressor genes, leading to genomic instability, which plays an important role in development of human cancer. In this regard, it is noteworthy that POLG encoding mtDNA polymerase γ, (a nuclear-encoded gene involved in the maintenance of the mitochondrial genome), is involved in development of cancer.…”

Section: Mitochondrial Regulation Of Genetic Changes In the Nuclear Gmentioning

confidence: 99%

Mitochondrial regulation of epigenetics and its role in human diseases

2012

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Section: Mitochondrial Regulation Of Genetic Changes In the Nuclear Gmentioning

confidence: 99%

Mitochondrial regulation of epigenetics and its role in human diseases

2012

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“…Folate is an essential cofactor for the de novo biosynthesis of nucleotides needed for DNA synthesis and plays a crucial role in DNA methylation, stability and integrity, and repair (1). Folate deficiency may cause defective DNA repair (3) and chromosomal fragile site expression (4), leading to chromosomal breaks (5) and micronucleus formation (4), thus conceivably increasing the risk of colorectal cancer.…”

Section: Introductionmentioning

confidence: 99%

A Prospective Study of Dietary Folate Intake and Risk of Colorectal Cancer: Modification by Caffeine Intake and Cigarette Smoking

Larsson

Giovannucci

Wolk

2005

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Epidemiologic evidence indicates an inverse association of folate intake with risk of colorectal cancer, but whether this association is modified by intake of caffeine (in coffee and tea) or cigarette smoking-factors that possibly interfere with folate-has not been studied. Thus, we examined whether the association between dietary folate intake and incidence of colorectal cancer is modified by caffeine intake and smoking. Cox proportional hazards modeling was used to estimate rate ratios relating dietary folate intake to colorectal cancer incidence among 61,433 women ages 40 to 75 years at recruitment into the Swedish Mammography Cohort in 1987 to 1990. From March 1987 through June 2004, a total of 805 incident cases of colorectal cancer were diagnosed. After controlling for age and other potential confounders, we observed an inverse association between dietary folate intake and risk of colon cancer (rate ratio for the highest versus the lowest quintile, 0.61; 95% confidence interval, 0.41-0.91; P trend = 0.02), but not of rectal cancer (rate ratio, 0.93; 95% confidence interval, 0.55-1.56; P trend = 0.97). The inverse association between dietary folate intake and colon cancer risk was most pronounced among smokers (P interaction = 0.03). We found no apparent modification of risk by caffeine intake. Findings from this population-based cohort study support an inverse association between dietary folate intake and risk of colon cancer and suggest that smokers might benefit most from a high dietary folate intake.

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“…The quarter of the population with the lowest fruit and vegetable intake has about twice the risk of developing most types of cancers as the quarter with the highest intake (13)(14)(15). Folate deficiency in humans induces extensive chromosome damage (16), fragile site expression (17), micronucleus formation (18,19), and increased uracil levels in bone marrow cell DNA (20).…”

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confidence: 99%

Folate deficiency causes uracil misincorporation into human DNA and chromosome breakage: Implications for cancer and neuronal damage

Blount

Mack

Wehr

et al. 1997

Proc. Natl. Acad. Sci. U.S.A.

1,280

902

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Folate deficiency causes massive incorporation of uracil into human DNA (4 million per cell) and chromosome breaks. The likely mechanism is the deficient methylation of dUMP to dTMP and subsequent incorporation of uracil into DNA by DNA polymerase. During repair of uracil in DNA, transient nicks are formed; two opposing nicks could lead to chromosome breaks. Both high DNA uracil levels and elevated micronucleus frequency (a measure of chromosome breaks) are reversed by folate administration. A significant proportion of the U.S. population has low folate levels, in the range associated with elevated uracil misincorporation and chromosome breaks. Such breaks could contribute to the increased risk of cancer and cognitive defects associated with folate deficiency in humans.

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Fragile Sites in Chromosomes: Possible Model for the Study of Spontaneous Chromosome Breakage

Cited by 65 publications

References 11 publications

Mitochondrial regulation of epigenetics and its role in human diseases

Mitochondrial regulation of epigenetics and its role in human diseases

A Prospective Study of Dietary Folate Intake and Risk of Colorectal Cancer: Modification by Caffeine Intake and Cigarette Smoking

Folate deficiency causes uracil misincorporation into human DNA and chromosome breakage: Implications for cancer and neuronal damage

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