Age at diagnosis of isolated unilateral retinoblastoma does not distinguish patients with and without a constitutional RB1 gene mutation but is influenced by a parent-of-origin effect

Schüler, Andreas; Weber, Stefanie; Neuhäuser, Markus; Jurklies, Christine; Lehnert, T.; Heimann, Heinrich; Rudolph, Günther; Jöckel, Karl‐Heinz; Bornfeld, Norbert; Lohmann, Dietmar

doi:10.1016/j.ejca.2004.12.022

Cited by 39 publications

(22 citation statements)

References 19 publications

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“…Previous studies focusing on the effect of parental origin of mutation on age at diagnosis of a variety of cancer associated disorders yielded inconsistent results. Schüler et al [15] reported that patients with somatic loss of the maternally inherited RB1 allele had an earlier age at diagnosis than patients with loss of the paternally inherited Retinoblastoma (RB1) allele. They concluded that age at diagnosis of retinoblastoma is modified at least in some families by a parent-of-origin effect.…”

Section: Discussionmentioning

confidence: 98%

Cancer risk in Jewish BRCA1 and BRCA2 mutation carriers: Effects of oral contraceptive use and parental origin of mutation

Bernholtz

Laitman

Kaufman

et al. 2011

Breast Cancer Res Treat

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BRCA1 and BRCA2 germline mutations substantially increase breast and ovarian cancer risk, yet penetrance is incomplete. The effects of oral contraceptives (OC) on breast cancer risk in mutation carriers are unclear, and the putative effect of parental origin of mutation on cancer risk has not been reported. Data on OC use and parental origin of the mutation were obtained at counseling from 888 BRCA1 (n = 638) or BRCA2 (n = 250) Jewish Israeli mutation carriers who were counseled and genotyped in a single medical center. Overall, 403 (45.4%) of participants had breast cancer (age at diagnosis 49.65 ± 12.2 years), 112 (12.6%) ovarian cancer (age at diagnosis 56.8 ± 10.8 years) and the rest (n = 373-42%) were asymptomatic carriers (age at counseling 40.7 ± 10.6 years). Of study participants, 472 (53.15%) ever used OC, and 298 used OC for at least 5 years. In 129 the mutation originated on the paternal side as judged by direct testing or obligate carriership and in 460 the mutation was maternally inherited. Multivariate logistic regression analysis, and stratifying for birth year, age at menarche, breast feeding, and number of births, showed that ever use of OC (Hazards Ratio-HR = 1.84 95% CI 1.465-2.314, P = 0.001) and paternal compared with maternal origin of mutation (OR = 1.55 95% CI 1.14-2.12, P = 0.006) were significantly associated with breast cancer and an earlier age at breast cancer diagnosis. The authors conclude that OC use and paternal origin of mutation affect breast cancer penetrance in Jewish BRCA1 and BRCA2 mutation carriers.

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Section: Discussionmentioning

confidence: 98%

Cancer risk in Jewish BRCA1 and BRCA2 mutation carriers: Effects of oral contraceptive use and parental origin of mutation

Bernholtz

Laitman

Kaufman

et al. 2011

Breast Cancer Res Treat

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“…In most of these patients the two RB1 gene mutations that initiated tumor development occurred in the somatic cells of the patient and are not detected in DNA from peripheral blood. However, about 12% of children with sporadic unilateral retinoblastoma have the hereditary form of retinoblastoma [Klutz et al, 1999;Richter et al, 2003;Schüler et al, 2005]. Optimal genetic counseling and planning of ophthalmologic surveillance in relatives depends on the identification of the oncogenic RB1 gene mutation in the index patient.…”

Section: Introductionmentioning

confidence: 99%

Spectrum of gross deletions and insertions in theRB1 gene in patients with retinoblastoma and association with phenotypic expression

et al. 2005

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Quantitative multiplex PCR and genomic real-time PCR were used to complete an RB1 mutation analysis in 57 of 433 and 72 of 262 patients with hereditary and isolated unilateral retinoblastoma, respectively. These patients were selected because in previous analyses, which focused mainly on the identification of point mutations, no RB1 mutation was found. We identified gross deletions and insertions in peripheral blood DNA from 26 of 57 patients (46%) with hereditary retinoblastoma, and in six of 72 patients (8.3%) with isolated unilateral disease. In addition, we identified 32 somatic mutations in tumor DNA from 31 of 72 patients (43%) with isolated unilateral retinoblastoma. Together with our previous results, we found that gross RB1 alterations were present in the peripheral blood DNA from 65 of 433 (15%) and 17 of 262 (6.5%) patients with bilateral or familial and isolated unilateral retinoblastoma, respectively. Including reported gross deletions, an analysis of the frequency of breakpoints per intron length shows higher densities in introns 13, 16, 23, and 24. Genotype-phenotype analyses showed that on the whole, carriers of gross deletions develop fewer retinoblastomas compared to patients who are heterozygous for other types of RB1 null mutations. Specifically, carriers of cytogenetic and submicroscopic whole gene deletions often have unilateral tumors only. By contrast, almost all patients with gross deletions with one breakpoint in RB1 have bilateral retinoblastoma.

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“…Die Essener Arbeitsgruppe konnte in einer Arbeit herausarbeiten, dass es keinen klaren Zusammenhang zwischen dem Erkrankungsalter von Patienten mit unilateralem Retinoblastom und der Genetik (Verlust des Rb1-Allels) gibt [16]. Das Alter der Patienten bei Diagnosestellung ist von vielen Faktoren abhängig und stellt somit das summative Resultat von Einflussgrößen wie dem Zeitpunkt der echten Tumorentstehung, der Tumorlage, des Tumorwachstums, der Aufmerksamkeit der Eltern und dem Zugang zu einer medizinischen Versorgung dar.…”

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Retinoblastom in Kenia

et al. 2014

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Age at diagnosis of isolated unilateral retinoblastoma does not distinguish patients with and without a constitutional RB1 gene mutation but is influenced by a parent-of-origin effect

Cited by 39 publications

References 19 publications

Cancer risk in Jewish BRCA1 and BRCA2 mutation carriers: Effects of oral contraceptive use and parental origin of mutation

Cancer risk in Jewish BRCA1 and BRCA2 mutation carriers: Effects of oral contraceptive use and parental origin of mutation

Spectrum of gross deletions and insertions in theRB1 gene in patients with retinoblastoma and association with phenotypic expression

Retinoblastom in Kenia

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