Background Breast cancer in men accounts for fewer than 1 % of all breast cancer cases diagnosed in men and women. Genes which predispose to male breast cancer include BRCA1 and BRCA2. The role of ...other genes is less clear. In Poland, 20 founder mutations in BRCA1, BRCA2, CHEK2, PALB2, NBN, RECQL are responsible for the majority of hereditary breast cancer cases in women, but the utility this genes panel has not been tested in men. Methods We estimated the prevalence of 20 alleles in six genes (BRCA1, BRCA2, CHEK2, PALB2, NBN, RECQL) in 165 Polish male breast cancer patients. We compared the frequency of selected variants in male breast cancer cases and controls. Results One of the 20 mutations was seen in 22 of 165 cases (13.3%). Only one BRCA1 mutation and two BRCA2 mutations were found. We observed statistically significant associations for PALB2 and CHEK2 truncating mutations. A PALB2 mutation was detected in four cases (OR = 11.66; p < 0.001). A CHEK2 truncating mutation was detected in five cases (OR = 2.93;p = 0.02). Conclusion In conclusion, we recommend that a molecular test for BRCA1, BRCA2, PALB2 and CHEK2 recurrent mutations should be offered to male breast cancer patients in Poland. Keywords: BRCA1, BRCA2, PALB2, CHEK2, NBN, RECQL, Mutation, Male breast cancer
There is emerging interest in the relationship between several serum micronutrients and the prognosis of patients with breast cancer. The relationship between serum zinc and copper levels and breast ...cancer prognosis is unclear. In our study, we included 583 patients with breast cancer diagnosed between 2008 and 2015 in the region of Szczecin, Poland. In a blood sample obtained before treatment, serum zinc and copper levels were quantified by mass spectroscopy. Each patient was assigned to one of four categories (quartiles) based on the distribution of the elements in the entire cohort. Patients were followed from diagnosis to death over a mean of 10.0 years. The 10-year overall survival was 58.3% for women in the highest and 82.1% for those in the lowest quartile of serum copper/zinc ratio (
< 0.001). The multivariate hazard ratio (HR) for breast cancer death was 2.07 (95% CI 1.17-3.63;
= 0.01) for patients in the highest quartile of serum copper/zinc ratio compared to those in the lowest. There is evidence that the serum zinc level and copper/zinc ratio provide an independent predictive value for overall survival and breast cancer-specific survival after breast cancer diagnosis.
In a prospective study, we measured the associations between three serum elements (Se, Zn and Cu) and the prognosis of 1475 patients with four different types of cancer (breast, prostate, lung and ...larynx) from University Hospitals in Szczecin, Poland. The elements were measured in serum taken after diagnosis and prior to treatment. Patients were followed from the date of diagnosis until death from any cause or until the last follow-up date (mean years of follow-up: 6.0-9.8 years, according to site). Kaplan-Meier curves were constructed for all cancers combined and for each cancer separately. Age-adjusted hazard ratios (HRs) were estimated using Cox regression. The outcome was all-cause mortality. A Se level in the highest quartile was also associated with a reduced mortality (HR = 0.66; 95%CI 0.49-0.88;
= 0.005) in all-cause mortality for all cancers combined. Zn level in the highest quartile was also associated with reduced mortality (HR = 0.55; 95%CI 0.41-0.75;
= 0.0001). In contrast, a Cu level in the highest quartile was associated with an increase in mortality (HR = 1.91; 95%CI 1.56-2.08;
= 0.0001). Three serum elements-selenium, zinc and copper-are associated with the prognosis of different types of cancer.
Mutations in BRCA1 and BRCA2 are well-established risk factors for breast and ovarian cancer. In Central-Eastern European counties, the founder mutations in the BRCA1 are responsible for a ...significant proportion of ovarian cancer cases, however, regional differences in the frequencies of various mutations may exist. The spectrum and frequency of BRCA1/2 mutations between ovarian cancer patients have not yet been precisely established in Belarus.
Two hundred fourteen consecutive unselected cases of ovarian cancer patients from the region of West Belarus were examined. We studied 13 founder mutations in BRCA1 (c.5266dupC, c.4035delA, c.5251C > T, c.181 T > G, c.676delT, c.68_69delAG, c.3700_3704delGTAAA, c.1687C > T, c.3756_3759delGTCT) and in BRCA2 (c.658_659delGT, c.7913_7917delTTCCT, c.3847_3848delGT, c.5946delT) characteristic for Central European population.
A BRCA1 or BRCA2 founder mutations were detected in 54 of the 214 (25.2%) ovarian cancer cases. The BRCA1 c.5266dupC mutation was detected in 28 patients, followed by c.4035delA mutation observed in 18 patients. BRCA1 c.3756_3759delGTCT, c.68_69delAG, and c.1687C > T were found in 3, 2, and 1 women, respectively. BRCA2 c.658_659delGT mutation was detected in 2 ovarian cancer patients. The median age of diagnosis of the 54 hereditary ovarian cancers was 57.5 years.
The frequency of 13 causative BRCA1 and BRCA2 founder mutations in West Belarus was higher than in other Slavic countries. Testing of BRCA1 (c.5266dupC, c.4035delA, c.3756_3759delGTCT, c.68_69delAG, c.1687C > T as well as c.181 T > G) and BRCA2 (c.658_659delGT) mutations should be considered an inexpensive and sensitive test panel for this population.
This study sought to assess the prevalence of common germline mutations in several genes engaged in the repair of DNA double-strand break by homologous recombination in patients with triple-negative ...breast cancers and hereditary non-triple-negative breast cancers. Tumors deficient in this type of DNA damage repair are known to be especially sensitive to DNA cross-linking agents (e.g., platinum drugs) and to poly(ADP-ribose) polymerase (PARP) inhibitors.
Genetic testing was performed for 36 common germline mutations in genes engaged in the repair of DNA by homologous recombination, i.e., BRCA1, BRCA2, CHEK2, NBN, ATM, PALB2, BARD1, and RAD51D, in 202 consecutive patients with triple-negative breast cancers and hereditary non-triple-negative breast cancers.
Thirty five (22.2%) of 158 patients in the triple-negative group carried mutations in genes involved in DNA repair by homologous recombination, while 10 (22.7%) of the 44 patients in the hereditary non-triple-negative group carried such mutations. Mutations in BRCA1 were most frequent in patients with triple-negative breast cancer (18.4%), and mutations in CHEK2 were most frequent in patients with hereditary non-triple-negative breast cancers (15.9%). In addition, in the triple-negative group, mutations in CHEK2, NBN, and ATM (3.8% combined) were found, while mutations in BRCA1, NBN, and PALB2 (6.8% combined) were identified in the hereditary non-triple-negative group.
Identifying mutations in genes engaged in DNA damage repair by homologous recombination other than BRCA1/2 can substantially increase the proportion of patients with triple-negative breast cancer and hereditary non-triple-negative breast cancer who may be eligible for therapy using PARP inhibitors and platinum drugs.
In a recent prospective study, we reported an association between a low serum selenium level and five-year survival among breast cancer patients. We now have updated the cohort to include 10-year ...survival rates. A blood sample was obtained from 538 women diagnosed with first primary invasive breast cancer between 2008 and 2015 in the region of Szczecin, Poland. Blood was collected before initiation of treatment. Serum selenium levels were quantified by mass spectroscopy. Each patient was assigned to one of four quartiles based on the distribution of serum selenium levels in the whole cohort. Patients were followed from diagnosis until death or last known alive (mean follow-up 7.9 years). The 10-year actuarial cumulative survival was 65.1% for women in the lowest quartile of serum selenium, compared to 86.7% for women in the highest quartile (
< 0.001 for difference). Further studies are needed to confirm the protective effect of selenium on breast cancer survival. If confirmed this may lead to an investigation of selenium supplementation on survival of breast cancer patients.
The role of the lifetime number of ovulatory cycles has not been evaluated in the context of BRCA‐associated ovarian cancer. Thus, we conducted a matched case–control study to evaluate the ...relationship between the cumulative number of ovulatory cycles (and contributing components) and risk of developing ovarian cancer in BRCA mutation carriers (1,329 cases and 5,267 controls). Information regarding reproductive and hormonal factors was collected from a routinely administered questionnaire. Conditional logistic regression was used to evaluate all associations. We observed a 45% reduction in the risk of developing ovarian cancer among women in the lowest vs. highest quartile of ovulatory cycles (OR = 0.55; 95% CI 0.41–0.75, p = 0.0001). Breastfeeding for more than 12 months was associated with a 38% (95% CI 0.48–0.79) and 50% (95% CI 0.29–0.84) reduction in risk among BRCA1 and BRCA2 mutation carriers, respectively. For oral contraceptive use, maximum benefit was seen with five or more years of use among BRCA1 mutation carriers (OR = 0.50; 95% CI 0.40–0.63) and three or more years for BRCA2 mutation carriers (OR = 0.42; 95% CI 0.22–0.83). Increasing parity was associated with a significant inverse trend among BRCA1 (OR = 0.87; 95% CI 0.79–0.96; p‐trend = 0.005) but not BRCA2 mutation carriers (OR 0.98; 95% CI 0.81–1.19; p‐trend = 0.85). A later age at menopause was associated with an increased risk in women with a BRCA1 mutation (OR trend = 1.18; 95% CI 1.03–1.35; p = 0.02). These findings support an important role of breastfeeding and oral contraceptive use for the primary prevention of ovarian cancer among women carrying BRCA mutations.
What's new?
The number of ovulatory cycles a woman has in her lifetime may influence her risk for ovarian cancer, though how cancer‐associated BRCA mutations factor into that relationship remains uncertain. Here, ovarian cancer risk was found to be significantly reduced among BRCA mutation carriers in the lowest quartile of ovulatory cycles. Likewise, risk was reduced in women with BRCA1 or BRCA2 mutations who used oral contraceptives for five or three years, respectively, or who breastfed for more than 12 months. The findings lend support to the idea that factors that suppress or interrupt ovulation protect against BRCA‐associated ovarian cancer.
BRCA1 and BRCA2 mutations contribute to both breast cancer and ovarian cancer worldwide. In Poland approximately 4% of patients with breast cancers and 10% of patients with ovarian cancer carry a ...mutation in BRCA1. The majority of mutations consist of three founder mutations. A rapid inexpensive test for these three mutations can be used to screen all Polish adults at a reasonable cost. In the region of Pomerania of North-western Poland nearly half a million tests have been performed, in large part through engaging family doctors and providing ready access to testing through the Pomeranian Medical University. The following commentary provides a history of genetic testing for cancer in Pomerania and the current approach to facilitating access to genetic testing at the Cancer Family Clinic for all adults living in the region.
The most prevalent type of cancer among males is prostate cancer. Survival is considered quite good, but it can be further improved when risk factors are optimized. One of these factors is ...micronutrients, including Se and Zn. To our knowledge, the interaction between Se and Zn and prostate cancer remains undescribed. This study aimed to investigate the optimal levels of selenium (Se) and zinc (Zn) and their impact on the survival of individuals diagnosed with prostate cancer. A total of 338 prostate cancer patients were enrolled in this study, which was conducted in Poland between 2009 and 2015. Mass spectrometry, which uses inductively coupled plasma mass, was used to assess serum element levels before treatment. The study participants were categorized into quartiles (QI-QIV) based on the distributions of Se and Zn levels observed among surviving participants. Cox regression was used to assess the association between serum Se and Zn levels and the survival of prostate cancer patients. Our results reveal the effect of combined Se and Zn levels on survival in prostate cancer patients (SeQI-ZnQI vs. SeQIV-ZnQIV; HR = 20.9). These results need further research to establish Se/Zn norms for different populations.
BRCA1 mutations substantially elevate the risks of breast and ovarian cancer. Various modifiers, including environmental factors, can influence cancer risk. Lead, a known carcinogen, has been ...associated with various cancers, but its impact on BRCA1 carriers remains unexplored. A cohort of 989 BRCA1 mutation carriers underwent genetic testing at the Pomeranian Medical University, Poland. Blood lead levels were measured using inductively coupled plasma mass spectrometry. Each subject was assigned to a category based on their tertile of blood lead. Cox regression analysis was used to assess cancer risk associations. Elevated blood lead levels (>13.6 μg/L) were associated with an increased risk of ovarian cancer (univariable: HR = 3.33; 95% CI: 1.23-9.00;
= 0.02; multivariable: HR = 2.10; 95% CI: 0.73-6.01;
= 0.17). No significant correlation was found with breast cancer risk. High blood lead levels are associated with increased risk of ovarian cancer in BRCA1 carriers, suggesting priority for preventive salpingo-oophorectomy. Potential risk reduction strategies include detoxification. Validation in diverse populations and exploration of detoxification methods for lowering lead levels are required.
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