Founder Mutations In BRCA1 Gene Research Articles

Serum concentration of iron as predictor of cancer risk among BRCA1 mutation carriers

The aim of the study is identification of correlations between the serum concentrations of iron and the risk of breast and/or ovarian cancer among female BRCA1 mutations carriers. The subjects selected for the trial were Polish women, positive for at least one of three founder mutations in BRCA1 gene dominating in Poland (5382insC, C61G, 4153delA). Persons with detected tumor were considered as cases and the others were considered as controls. One case and two controls were paired regarding many criteria (e.g. age, family cancer history, cigarettes smoking) to achieve the maximum of similarity between them. The proportion of cases and control in the first quartile was taken as a reference to calculate the odds ratio, confidence interval and p-value of the multivariate conditional logistic regression. The iron was quantitatively measured by ICP-MS (Inductively Coupled Plasma Mass Spectrometry), (model Elan DRC-e 6100 th, PerkinElmer). This study shows that concentration levels of iron in blood serum are a strong factors associated with an additionally increased risk of breast and ovarian cancer among BRCA1 mutation carriers. For iron concentration, all quartiles above the first one had a decreased risk of breast or ovarian cancer. The results are shown in Table ​Table11. Table 1 Iron concentration in each quartile Similarly, high ratios of iron to selenium were significantly associated with disease protection which is shown in Table ​Table22. Table 2 Ratios between iron and selenium

Iron and breast cancer risk

The aim of the study is identification of correlations between the serum concentrations of iron and the risk of breast cancer among female BRCA1 mutations carriers and unselected breast cancer patients. The first group (99 triplet) selected for the trial were Polish women, positive for at least one of three founder mutations in BRCA1 gene dominating in Poland (5382insC, C61G, 4153delA). Serum was collected at the time of breast cancer diagnosis. Persons with detected tumor were considered as cases and the others were considered as controls. One case and two controls were paired regarding many criteria (e.g. age, family cancer history, cigarettes smoking, adnexectomy status ) to achieve the maximum of similarity between them. The subjects of the second group (28 triplet) selected for the trial were Polish women, positive for at least one of three founder mutations in BRCA1 gene. Serum was collected 1-2 years before breast cancer diagnosis. One case and two controls were matched for year of birth, past history of cancer, adnexectomy status and cigarettes smoking to achieve the maximum of similarity between them. The subjects of the third group were unselected cancer for the trial were Polish women. Serum was collected during breast cancer diagnosis before treatment. One case and one control were matched for year of birth (+/- 3 years), number and location of cancer among Io relatives, smoking-the number of pack years (+/- 10%), adnexectomy status, CHEK2 mutation. The proportion of cases and control in the first quartile was taken as a reference to calculate the odds ratio, confidence interval and p-value of the multivariate conditional logistic regression. The iron was quantitatively measured by ICP-MS (Inductively Coupled Plasma Mass Spectrometry), (model Elan DRC-e 6100 th, PerkinElmer). This study shows that concentration levels of iron in blood serum are a strong factors associated with an additionally increased risk of breast cancer among BRCA1 mutation carriers and unselected breast cancer patients. For iron concentration in BRCA1 carriers (serum collected at the time of breast cancer diagnosis) all quartiles above the first one had a decreased risk of breast cancer. The results are shown in Table ​Table11. Table 1 Association between Fe serum concentration and risk of breast cancer in BRCA 1 carriers (serum collected at the time of breast cancer diagnosis). For iron concentration in BRCA1 carriers (serum collected 1-2 years before breast cancer diagnosis) the last quartile had a decreased risk of breast cancer. The results are shown in Table ​Table22. Table 2 Association between Fe serum concentration and risk of breast cancer in BRCA 1 carriers (serum collected 1-2 years before breast cancer diagnosis). Individuals classified in the III and IV quartile had lower risk of breast cancer however results were statistically insignificant. The strongest result and lowest cancer risk was for Fe > 1350 μg/l (OR= 0,289, p= 0,0426) For iron concentration in unselected breast cancer patients (serum was collected during breast cancer diagnosis before treatment) all quartiles were statistically insignificant. The results are shown in Table ​Table33. Table 3 Association between Fe serum concentration and risk of breast cancer Individuals classified in the III quartile had lower risk of breast cancer however results were statistically insignificant. The strongest result and lowest cancer risk was for Fe > 1000 μg/l (OR= 0,6698, p= 0,25554). For iron concentration in unselected breast cancer patients (serum was collected during breast cancer diagnosis before treatment) before 55 years old, third quartile had a decreased risk of breast cancer. The results are shown in Table ​Table44. Table 4 Association between Fe serum concentration and risk of cancer in group of patients < 55 years old. Individuals classified in the III quartile had lower risk of breast cancer (OR=0,248, p=0,019); The strongest result and lowest cancer risk was for Fe concentration higher than 987 μg/l (III quartile) ; max 1285 μg/l (III quartile)

Serum concentration of selected macro- and microelements and their correlation with the risk of breast and ovarian cancer among BRCA1 mutation carriers

The study was conducted to determine the correlations between serum concentration of selected macro- and microelements, namely: magnesium (Mg), copper (Cu), zinc (Zn), arsenic (As), calcium (Ca), cadmium (Cd) chromium (Cr) and selenium (Se) with increased or decreased predisposition to breast and ovarian cancer. The subjects selected for the trial were Polish women, positive for at least one of three founder mutations in BRCA1 gene dominating in Poland (5382insC, C61G, 4153delA). Persons with detected tumor were considered as cases and the others were considered as controls. One case and two controls were paired regarding many criteria (e.g. age, family cancer history, cigarettes smoking) to achieve the maximum of similarity between them. All the elements were quantitatively measured simultaneously in diluted serum samples by inductively coupled plasma mass spectrometry (ICP-MS) using mass spectrometer (Elan DRC-e, PerkinElmer) in standard mode (Mg, Cu, Zn) and in DRC mode (As, Ca, Cd, Cr) with methane as a reaction gas, for removing polyatomic interferences in measurement. Statistically significant differences have been found for arsenic and zinc. In case of arsenic, individuals classified in the second and fourth quartile had a significantly higher risk of breast or ovarian cancer than those in the first quartile. In case of zinc a significantly lower risk of breast or ovarian cancer was observed among individuals classified in the second quartile. The data are shown in Table ​Table11. Table 1 Arsenic and zinc concentration in each quartiles Apart from the influence of single elements some interactions from combinations of arsenic, magnesium, cadmium, zinc and calcium with selenium were also analyzed. The combinations with statistically significant differences between quartiles in the disease risk are shown in Table ​Table22. Table 2 Ratios between analyzed elements and selenium

Arsenic (As) and breast cancer risk

The study was conducted to determine the correlations between serum concentration of arsenic (As) with increased or decreased predisposition to breast and ovarian cancer.

Novel and common BRCA1 mutations in familial breast/ovarian cancer patients from Lithuania

The germline mutations in the BRCA1 (MIM 113705) and BRCA2 (MIM600185) genes account for the majority of hereditary breast and ovarian cancers cases. Founder mutations in BRCA1 gene have been recently described in Eastern Baltic Sea region, with variable distribution in Baltic (Latvian [1] and Lithuanian [2]) and Slavic (Polish [3], Belorussian [4], Russian [5]) populations, accounting for 80–90% of all mutations. However, data about its incidence in Lithuania are inconclusive and based on one study where only three mutations were tested in BRCA1 gene [2]. Here we present the complexity of BRCA1 gene mutation profile in familial breast and/or ovarian cancer index cases referred to Vilnius University Hospital Santariskiu Clinics from 1 year period (2006–2007).

Male to female ratio among offspring of BRCA1 mutation carriers

To the editor: It has been reported that the RING domain of BRCA1 protein interacts with the Xist RNA in mammalian cells, thereby influencing X chromosome inactivation [1]. Lee et al. showed that in mice, defective X-chromosome inactivation changes the sex ratio of offspring [2]. In this context it has been suggested that BRCA1 insufficiency may reduce the ability of Xist RNA to accumulate along the X chromosome and lead to a skewed sex ratio in children [3]. In light of this findings, we were interested in the results of de la Hoya and colleagues, who reported an increased ratio of female to male offspring of BRCA1 mutation carriers, but not of BRCA2 mutation carriers [4]. It is well known that studies such as these may be influenced by possible ascertainment biases [5]; in particular if women with daughters are more likely to seek genetic testing than women with only boys or with no children. Recently, several authors observed only slight, statistically insignificant excesses of female offspring of BRCA1 or BRCA2 carriers, suggesting that the observed sex ratio skew against male births might be due to ascertainment bias [6–9]. Studies in which BRCA carriers are ascertained within a consecutive series of breast or ovarian cancer cases, and are unselected for family histories and for sex distribution of children, are ideally suited to study this question as they are free from ascertainment bias [10]. In the course of a national breast cancer survey, through cancer registry of pathology departments we identified 4596 consecutive women with breast cancer diagnosed before age 50 at one of 18 centers situated throughout Poland from 1996–2003. In each center over 70% of affected women offered blood for genetic testing. We were able to obtain a DNA sample for BRCA1 analysis on 3568 of these patients. Three founder mutations in BRCA1 gene (5382insC, C61G, and 4153delA) which cover about 90% of detectable BRCA1/2 mutations in Poland [11] were studied. Among these women 198 mutation carriers were identified (5.54%). Through pedigree review we identified 189 sons and 172 daughters of these 198 BRCA1 mutation carrier women. The male to female ratio was 1.10. According to the Polish Main Statistic Office the male to female ratio in general population at birth is 1.06 [12]. Thus the difference is insignificant (v = 0.08; p = 0.77). In conclussion, our data set, which was obtained on unselected group of female BRCA1 (5382insC, C61G, and 4153delA) mutation carriers, strongly indicate that there is no evidence of sex ratio distoration in offspring. This supports the statement that rather ascertainment bias than X-chromosome inactivation was a cause of observed before a skewed sex ratio between offspring of BRCA1 carriers.