Selenium has attracted attention because of its antioxidant properties. Antioxidants protects cells from damage. Certain breakdown products of selenium are believed to prevent tumor growth by ...enhancing the immune cell activity and suppressing the development of tumor blood vessels. In this observational study, selenium level was measured in a series of patients from Poland and Estonia to determine a correlation between levels of this microelement and colorectal cancer risk.
A total of 169 colorectal cancer patients and 169 healthy controls were enrolled in the study after obtaining their informed consent. Selenium level in the blood serum was measured using Graphite Furnace Atomic Absorption Spectrometry (GFAAS). The statistical analysis was performed by Fisher's exact test.
The threshold point of selenium level was 55 μg/l and 65 μg/l for Poland and Estonia respectively, for an increase in cancer risk. The lower levels of selenium were associated with greater risk of colorectal cancer.
The result reveals a significant strong association between low selenium level and the colorectal cancer risk in both Estonian and Polish populations.
Purpose
Cis
-acting regulatory SNPs resulting in differential allelic expression (DAE) may, in part, explain the underlying phenotypic variation associated with many complex diseases. To investigate ...whether common variants associated with DAE were involved in breast cancer susceptibility among
BRCA1
and
BRCA2
mutation carriers, a list of 175 genes was developed based of their involvement in cancer-related pathways.
Methods
Using data from a genome-wide map of SNPs associated with allelic expression, we assessed the association of ~320 SNPs located in the vicinity of these genes with breast and ovarian cancer risks in 15,252
BRCA1
and 8211
BRCA2
mutation carriers ascertained from 54 studies participating in the Consortium of Investigators of Modifiers of
BRCA1/2
.
Results
We identified a region on 11q22.3 that is significantly associated with breast cancer risk in
BRCA1
mutation carriers (most significant SNP rs228595
p
= 7 × 10
−6
). This association was absent in
BRCA2
carriers (
p
= 0.57). The 11q22.3 region notably encompasses genes such as
ACAT1
,
NPAT
, and
ATM
. Expression quantitative trait loci associations were observed in both normal breast and tumors across this region, namely for
ACAT1
,
ATM
, and other genes. In silico analysis revealed some overlap between top risk-associated SNPs and relevant biological features in mammary cell data, which suggests potential functional significance.
Conclusion
We identified 11q22.3 as a new modifier locus in
BRCA1
carriers. Replication in larger studies using estrogen receptor (ER)-negative or triple-negative (i.e., ER-, progesterone receptor-, and HER2-negative) cases could therefore be helpful to confirm the association of this locus with breast cancer risk.
Individuals carrying pathogenic mutations in the BRCA1 and BRCA2 genes have a high lifetime risk of breast cancer. BRCA1 and BRCA2 are involved in DNA double-strand break repair, DNA alterations that ...can be caused by exposure to reactive oxygen species, a main source of which are mitochondria. Mitochondrial genome variations affect electron transport chain efficiency and reactive oxygen species production. Individuals with different mitochondrial haplogroups differ in their metabolism and sensitivity to oxidative stress. Variability in mitochondrial genetic background can alter reactive oxygen species production, leading to cancer risk. In the present study, we tested the hypothesis that mitochondrial haplogroups modify breast cancer risk in BRCA1/2 mutation carriers.
We genotyped 22,214 (11,421 affected, 10,793 unaffected) mutation carriers belonging to the Consortium of Investigators of Modifiers of BRCA1/2 for 129 mitochondrial polymorphisms using the iCOGS array. Haplogroup inference and association detection were performed using a phylogenetic approach. ALTree was applied to explore the reference mitochondrial evolutionary tree and detect subclades enriched in affected or unaffected individuals.
We discovered that subclade T1a1 was depleted in affected BRCA2 mutation carriers compared with the rest of clade T (hazard ratio (HR) = 0.55; 95% confidence interval (CI), 0.34 to 0.88; P = 0.01). Compared with the most frequent haplogroup in the general population (that is, H and T clades), the T1a1 haplogroup has a HR of 0.62 (95% CI, 0.40 to 0.95; P = 0.03). We also identified three potential susceptibility loci, including G13708A/rs28359178, which has demonstrated an inverse association with familial breast cancer risk.
This study illustrates how original approaches such as the phylogeny-based method we used can empower classical molecular epidemiological studies aimed at identifying association or risk modification effects.
Population-based genome wide association studies have identified a locus at 9p22.2 associated with ovarian cancer risk, which also modifies ovarian cancer risk in BRCA1 and BRCA2 mutation carriers. ...We conducted fine-scale mapping at 9p22.2 to identify potential causal variants in BRCA1 and BRCA2 mutation carriers. Genotype data were available for 15,252 (2,462 ovarian cancer cases) BRCA1 and 8,211 (631 ovarian cancer cases) BRCA2 mutation carriers. Following genotype imputation, ovarian cancer associations were assessed for 4,873 and 5,020 SNPs in BRCA1 and BRCA 2 mutation carriers respectively, within a retrospective cohort analytical framework. In BRCA1 mutation carriers one set of eight correlated candidate causal variants for ovarian cancer risk modification was identified (top SNP rs10124837, HR: 0.73, 95%CI: 0.68 to 0.79, p-value 2× 10-16). These variants were located up to 20 kb upstream of BNC2. In BRCA2 mutation carriers one region, up to 45 kb upstream of BNC2, and containing 100 correlated SNPs was identified as candidate causal (top SNP rs62543585, HR: 0.69, 95%CI: 0.59 to 0.80, p-value 1.0 × 10-6). The candidate causal in BRCA1 mutation carriers did not include the strongest associated variant at this locus in the general population. In sum, we identified a set of candidate causal variants in a region that encompasses the BNC2 transcription start site. The ovarian cancer association at 9p22.2 may be mediated by different variants in BRCA1 mutation carriers and in the general population. Thus, potentially different mechanisms may underlie ovarian cancer risk for mutation carriers and the general population.
Purpose: Few studies have evaluated the role of micronutrients or trace elements in breast cancer development among BRCA1 mutation carriers. To investigate a possible role of dietary and ...environmental exposures on cancer risk, we undertook an exploratory study, using a matched case-control design (n = 48 cases and 96 controls), to evaluate the relationships between plasma levels of 14 micronutrients and breast cancer risk among BRCA1 mutation carriers in Poland. Methods: We estimated the univariate odds ratios (OR) and 95 % confidence intervals (CI) for breast cancer associated with plasma levels for each of 14 micronutrients. Results: Of the 14 analytes quantified, significant differences between cases and controls were seen for two (iron and retinol; p = 0.009 and p = 0.03, respectively). Women in the highest tertile of plasma iron had a 57 % lower risk, compared with those in the lowest quartile (OR = 0.43; 95 % CI 0.18-1.04; p for trend = 0.06). Increasing antimony levels were associated with an increased risk of breast cancer (p for trend = 0.05). Women in the highest tertile had a 2.43-fold increase in breast cancer risk compared with women in the lowest tertile (OR = 2.43; 95 % CI 1.00-5.91). Conclusions: This study provides some preliminary evidence regarding a role of diet, specifically iron and antimony, in the etiology of BRCA1-associated breast cancer. Prospective studies are necessary to confirm these findings.
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