Serum selenium levels predict survival after breast cancer.

BACKGROUND: Studies have reported an inverse relationship between serum selenium levels and cancer incidence, but the impact of low serum selenium status on survival after a diagnosis of breast cancer has not been established. METHODS: We obtained a blood sample from 546 women diagnosed with a first primary invasive breast cancer between 2008 and 2015 in the region of Szczecin, Poland. Blood was collected after diagnosis, but prior to treatment. Serum selenium was quantified by mass spectroscopy and each patient was assigned to one of four categories (quartiles) based on the distribution in the entire cohort. Patients were followed from diagnosis to death over a mean follow-up of 3.8 years. Vital status was obtained by linkage to the Polish National Death Registry. RESULTS: The 5-year overall actuarial survival was 68.1% for women in the lowest (< 64.4 µg/L) and 82.5% for those in the highest (> 81.0 µg/L) quartile of serum selenium. In an adjusted analysis, the hazard ratio for death was 2.49 (95%CI 1.53-4.04; P = 0.0002) for patients in the lowest quartile of serum selenium, compared to those in all other quartiles. The effect of low selenium on breast cancer-specific mortality was stronger for women who were past smokers (HR 6.03; 95%CI 1.96-18.6; P = 0.0002). CONCLUSIONS: This study suggests that a selenium level in excess of 64.4 µg//L might be beneficial for women undergoing treatment for breast cancer and that selenium supplementation to achieve this level may favorably impact the outcome. Further studies are needed to confirm this association and to evaluate the impact of selenium supplementation on breast cancer survival among women with low post-diagnostic selenium levels.

A Matched Case-Control Study of Risk Factors for Breast Cancer Risk in Vietnam.

Background. Vietnam has a low age-standardized incidence of breast cancer, but the incidence is rising rapidly with economic development. We report data from a matched case-control study of risk factors for breast cancer in the largest cancer hospital in Vietnam. Methods. 492 incident breast cancer cases unselected for family history or age at diagnosis and 1306 control women age 25-75 were recruited from the National Cancer Hospital (BVK), Hanoi. Structured interviews were conducted and pathology data was centrally reported at the National Cancer Hospital of Vietnam, in Hanoi. Results. Our analysis included 294 matched pairs. Mean age at diagnosis was 46.7 years. Lower mean parity, older age at first parity, increasing weight and BMI at age 18, and increasing BMI at diagnosis were positively correlated with breast cancer cases compared to controls. Age at first menarche and duration of breastfeeding were not statistically different between cases and controls. Conclusions. In this study we demonstrate that breast cancer in Vietnam is associated with some but not all of the published risk factors from Western populations. Our data is consistent with other studies of breast cancer in Asian populations.

Prognostic value of INPP4B protein immunohistochemistry in ovarian cancer.

PURPOSE OF INVESTIGATION: Ovarian cancer is associated with poor prognosis and altered protein expression patterns may be useful for identifying patients likely to have poor disease outcomes. The impact of altered INPP4B protein expression on prognosis is unclear. The aim of this study was to evaluate the implication of INPP4B expression changes in a large series of ovarian cancer tissue samples. MATERIALS AND METHODS: Tissue microarrays were constructed from 599 epithelial ovarian tumors and stained with antibodies for INPP4B, p53, and PTEN. Proportional hazard models were used to estimate survival hazard ratios (HRs) associated with altered protein expression. RESULTS: Seventy-nine percent of the ovarian cancers demonstrated loss of INPP4B, whereas 53% showed aberrant p53 expression (i.e., complete loss of p53 or over-expression of p53) and 8% showed loss of PTEN. INPP4B was frequently lost in serous and endometrioid cancer subtypes, aberrant p53 expression was most common among serous subtype, and loss of PTEN was most common among endometrioid tumors (p for all three proteins across histologic subtypes ≤ 0.0001). INPP4B loss or aberrant p53 expression were both associated with increased mortality (HR = 1.84; 95% CI 1.27 - 2.68 and HR = 3.10; 95% CI 2.33 - 4.11, respectively); however, in multivariate models, only the relationship with p53 achieved statistical significance (HR = 1.20; 95% CI 0.82 - 1.76 for INPP4B and HR = 1.73; 95% CI 1.28 - 2.34 for p53). Conclusion: The INPP4B protein is frequently lost in serous and endometrioid subtypes of ovarian cancer. A possible prognostic role of INPP4B for endometrioid ovarian tumors requires further evaluation.

BRCA1 mRNA levels following a 4-6-week intervention with oral 3,3'-diindolylmethane.

BACKGROUND: Haploinsufficiency may contribute to the development of breast cancer among women with a BRCA1 mutation. Thus, interventions that enhance BRCA1 expression may represent avenues for prevention. Studies have shown that 3,3'-diindolylmethane (DIM) can upregulate BRCA1 expression in breast cancer cells. This has yet to be demonstrated in vivo. METHODS: We conducted a study to evaluate the ability of oral DIM to upregulate BRCA1 mRNA expression in white blood cells. A total of 18 women were enroled in the study, including 13 BRCA1 mutation carriers who received 300 mg per day of Rx Balance BioResponse DIM for 4-6 weeks (intervention group) and 5 BRCA1 mutation carriers who did not take DIM (control group). BRCA1 mRNA expression was assessed at baseline and at 4-6 weeks by real-time, quantitative PCR and the relative change in BRCA1 mRNA expression (that is, 2(-ΔΔCT)) was calculated. RESULTS: The relative change in BRCA1 mRNA expression among women in the intervention group achieved borderline significance (P paired t-test=0.05). In the intervention group, BRCA1 mRNA expression increased in 10 of the participants, decreased in 2 and remained unchanged in 1 of the participants following DIM intervention (P sign test=0.02). On average, women in the intervention group experienced a 34% increase in BRCA1 mRNA expression (range -24 to 194%). There was no significant difference in the relative change in BRCA1 mRNA expression among women in the control group (P paired t-test=0.45). CONCLUSIONS: Under the tested conditions, oral DIM was associated with an increase in BRCA1 mRNA expression in women with a BRCA1 mutation. The possibility of mitigating the effect of an inherited deleterious BRCA1 mutation by increasing the physiologic expression of the gene and normalising protein levels represents a clinically important paradigm shift in the prevention strategies available to these high-risk women. Future studies with a larger sample size and higher doses of DIM are warranted.

Dietary betaine and choline intake are not associated with risk of epithelial ovarian cancer.

Evidence suggests that nutrients involved in one-carbon metabolism are implicated in ovarian cancer etiology. No studies have evaluated the role of choline, and that of its metabolite, betaine. We prospectively examined the relationship between the intake of these nutrients and ovarian cancer risk among 159 957 participants from the Nurses' Health Study (NHS) and NHSII. The average nutrient intake was assessed every 2-4 years beginning in 1984 (for NHS) and in 1991 (for NHSII). With up to 22 years of follow-up per cohort, 526 incident cases of ovarian cancer were diagnosed. There were no associations between total choline, betaine, as well as choline plus betaine intake and ovarian cancer risk (for example, relative risk, top vs bottom quintile of choline=0.98; 95% confidence interval: 0.73-1.31; P(trend)=0.81). Results did not vary by alcohol consumption, folate intake or after the exclusion of cases diagnosed during the 4-year period after dietary assessment. These data provide little evidence for a role of these nutrients in ovarian cancer etiology.

DNA repair capacity as a possible biomarker of breast cancer risk in female BRCA1 mutation carriers.

The BRCA1 gene product helps to maintain genomic integrity through its participation in the cellular response to DNA damage: specifically, the repair of double-stranded DNA breaks. An impaired cellular response to DNA damage is a plausible mechanism whereby BRCA1 mutation carriers are at increased risk of breast cancer. Hence, an individual's capacity to repair DNA may serve as a useful biomarker of breast cancer risk. The overall aim of the current study was to identify a biomarker of DNA repair capacity that could distinguish between BRCA1 mutation carriers and non-carriers. DNA repair capacity was assessed using three validated assays: the single-cell alkaline gel electrophoresis (comet) assay, the micronucleus test, and the enumeration of gamma-H2AX nuclear foci. DNA repair capacity of peripheral blood lymphocytes from 25 cancer-free female heterozygous BRCA1 mutation carriers and 25 non-carrier controls was assessed at baseline and following cell exposure to gamma-irradiation (2 Gy). We found no significant differences in the mean tail moment, in the number of micronuclei or in the number of gamma-H2AX nuclear foci between the carriers and non-carriers at baseline, and following gamma-irradiation. These data suggest that these assays are not likely to be useful in the identification of women at a high risk for breast cancer.

Posttraumatic stress reactions among children following the Athens earthquake of September 1999.

The objective of the present study was to assess symptoms of posttraumatic stress disorder (PTSD), depression and anxiety among children 6 months after they had been exposed to an earthquake (EQ) affecting the northwestern suburbs of Athens in September 1999. A total of 115 children attending two elementary schools located at the epicentre of the EQ were assessed. A group of 48 children not affected by the EQ attending a school not affected by the EQ were used as controls. The children and their parents completed a number of questionnaires. Overall, there was a high rate (78%) of severe to mild PTSD symptoms in the EQ exposed group. Additionally, a substantial proportion of these children scored above criteria (32%) for depression compared to the control group (12.5%). Severe or moderate symptoms of PTSD were associated with high scores of depression (p = 0.002). The relationship between PTSD symptoms and anxiety was limited to the "avoidance" factor of the anxiety questionnaire (p = 0.029). Those who were most likely to be affected were children alone at the time of the EQ, and children who sustained injuries. In summary, countries where EQs are frequent should be prepared to offer psychological support to a substantial proportion of children presenting with PTSD and depressive symptoms and should educate and prepare children to cope with these events.