Association of vitamin D deficiency and insulin resistance with breast cancer in premenopausal Algerian women: A cross-sectional study.

BACKGROUND: Low 25(OH)D levels are mainly related to breast cancer (BC) risk in postmenopausal women, while the impact of insulin resistance (IR) on BC prognosis is controversial. OBJECTIVE: Considering the high prevalence of BC in younger Algerian women, this cross-sectional study analyzed whether vitamin D status and IR are biomarkers for breast tumor status in premenopausal women. METHODS: In 96 women (mean age, 40.96±0.65years) newly diagnosed with BC, tumor status was determined immunohistochemically, classified by molecular subtype, then correlated with body-mass index, total plasma 25(OH)D, insulin and glucose levels and HOMA-IR, using Chi2, Student t, Spearman and ANOVA tests and multivariate logistic regression. RESULTS: A total of 66 of the 96 patients (68.75%) showed vitamin D deficiency (9.74ng/mL). Overweight and obese patients with HOMA-IR>2.5, positive for HER2 and with high Ki-67 index had the most severe vitamin D deficiency. There was a significant association between vitamin D deficiency, high Ki-67 index (OR, 14.55; 95% CI: 3.43-82.59; P=0.00078) and IR (OR, 4.99; 95% CI: 1.27-24.47; P=0.03), and between IR and HER2-positivity (OR, 3.23; 95% CI: 1.05-10.56; P=0.04). CONCLUSIONS: Vitamin D deficiency and IR are potential biomarkers for poorer prognosis in BC patients, independently of and/or synergically with high Ki-67 index and HER2-positivity in premenopausal overweight or obese women. The potential relationship of vitamin D receptor gene expression with breast cancer survival in Algerian patients will be investigated in a large cohort.

Clinico-epidemiological profile and redox imbalance of lung cancer patients in Algeria.

Hypothesis: How are the epidemiologic repartition and the physiopathology of lung cancer (LC) in Algeria? Objective: Our study aimed to establish the clinico-epidemiological profile and evaluate redox imbalance in Algerian patients with LC. Methods and results: Our study concerned 94 Algerian patients with LC treated at two hospitals of Algiers, the capital of Algeria. The clinico-epidemiological profile was established. Moreover, the redox imbalance was evaluated by dosing oxidative stress (OS) parameters in tumor tissues and blood. We noted that the average age was 62.06 years, and 79 among the 94 patients were male, 94.59% of which were smokers. The most common histological type was adenocarcinoma (45.45% of cases), followed by squamous cell carcinoma (37.88%) small-cell carcinoma (4.86%) and other histological types (6.67%), while the most frequent clinical stage was IV (66.95 %). 23 of the 94 patients were exposed to particular risk factors such as masonry products, metal mechanics, coal smoke and so forth. In other respects, the OS parameters: NO (Nitrogen monoxide), AOPP (Advanced Oxidation Protein Products) and MDA (Malondialdehyde) were higher in tumor tissues compared to peritumoral stroma (control), unlike the catalase activity. Otherwise, AOPP and MDA were significantly higher in patients' blood than in healthy control blood, in contrast to the catalase activity. Discussion: The LC has a heterogeneous repartition regarding the sex, age, histological types, the smoking status and professional exposition to risk factors in the Algerian population. Moreover, the oxidative stress impacts the physiopathology of LC.

BRCA1 and BRCA2 unclassified variants and missense polymorphisms in Algerian breast/ovarian cancer families.

BACKGROUND: BRCA1 and BRCA2 germline mutations predispose heterozygous carriers to hereditary breast/ovarian cancer. However, unclassified variants (UVs) (variants with unknown clinical significance) and missense polymorphisms in BRCA1 and BRCA2 genes pose a problem in genetic counseling, as their impact on risk of breast and ovarian cancer is still unclear. The objective of our study was to identify UVs and missense polymorphisms in Algerian breast/ovarian cancer patients and relatives tested previously for BRCA1 and BRCA2 genes germline mutations analysis. METHODS: We analyzed 101 DNA samples from 79 breast/ovarian cancer families. The approach used is based on BRCA1 and BRCA2 sequence variants screening by SSCP or High-Resolution Melting (HRM) curve analysis followed by direct sequencing. In silico analyses have been performed using different bioinformatics programs to individualize genetics variations that can disrupt the BRCA1 and BRCA2 genes function. RESULTS: Among 80 UVs and polymorphisms detected in BRCA1/2 genes (33 BRCA1 and 47 BRCA2), 31 were new UVs (10 BRCA1 and 21 BRCA2), 7 were rare UVs (4 BRCA1 and 3 BRCA2) and 42 were polymorphic variants (19 BRCA1 and 23 BRCA2). Moreover, 8 new missense UVs identified in this study: two BRCA1 (c.4066C>A/p.Gln1356Lys, c.4901G>T/p.Arg1634Met) located respectively in exons 11 and 16, and six BRCA2 (c.1099G>A/p.Asp367Asn, c.2636C>A/p.Ser879Tyr, c.3868T>A/p.Cys1290Ser, c.5428G>T/p.Val1810Phe, c.6346C>G/p.His2116Asp and c.9256G>A/p.Gly3086Arg) located respectively in exons 10, 11 and 24, show a damaging PSIC score yielded by PolyPhen2 program and could be pathogenic. In addition, 5 new BRCA} missense UVs out of six that were found to be damaging by PolyPhen2 program, also were deleterious according to SIFT program. The rare BRCA1 UV c.5332G>A/p.Asp1778Asn was found here for the first time in co-occurrence in trans with the deleterious BRCA1 mutation c.798_799delTT/p.Ser267LysfsX19 in young breast cancer patient. Moreover, 10 new identified intronic variants with unknown clinical significance (3 BRCA1 and 7 BRCA2) in the present study, could be considered as benign, because GeneSplicer, SpliceSiteFinder and MaxEntScan prediction programs show no splice site alteration for these variants. Several missense polymorphisms of BRCA1 c.2612C>T/p.Pro871Leu, c.3548A>G/p.Lys1183Arg, c.4837A>G/p.Ser1613Gly and BRCA2 c.865A>C/p.Asn289His, c.1114A>C/p.Asn372His, c.2971A>G/p.Asn991Asp, c.7150C>A/p.Gly2384Lys have been identified with high frequency in patients who were tested negative for BRCA1 and BRCA2 mutations. These missense polymorphisms could have a role as susceptibility breast cancer markers in Algerian breast/ovarian cancer families where pathological BRCA1 and BRCA2 mutations were not present. CONCLUSIONS: For the first time, UVs and missense polymorphisms in BRCA1 and BRCA2 genes have been identified in Algerian breast/ovarian cancer families. Evaluation of breast/ovarian cancer risk induced by the eight new missense UVs and common polymorphisms detected in our present work is on going in a larger study.

BRCA1 and BRCA2 germline mutation spectrum in hereditary breast/ovarian cancer families from Maghrebian countries.

OBJECTIVE: To summarize the knowledge about BRCA1 and BRCA2 germline mutation spectrum in Maghrebian countries. METHODS: We performed a systematic review of the literature to determine the impact of BRCA1 and BRCA2 mutations on hereditary breast/ovarian cancer in the Maghrebian population from Algeria, Morocco and Tunisia. We searched all available data published in Pubmed, Scopus, Cancerlit® databases and other scientific literatures sources. RESULTS: Pathogenic mutations in BRCA1 gene were detected by DNA sequencing in 17.43% (34/195) of analyzed breast/ovarian cancer families from Algeria, Morocco and Tunisia. One common mutation c.798_799delTT was identified in the BRCA1 gene with a frequency of 5.12%. Pathogenic BRCA2 mutations were identified in 11 out 146 families (7.53%). A new common BRCA2 pathogenic mutation c.7235_7236insG was detected in Algerian and Moroccan families. CONCLUSIONS: The Maghrebian population from Algeria, Morocco and Tunisia has just been started to be extensively studied; consequently knowledge of the prevalence and spectrum of BRCA1 and BRCA2 mutations in these populations is getting dense. The implications of these new findings in regard to genetic testing and counseling are substantial for patients and families at risk.

BRCA1 and BRCA2 germline mutations screening in Algerian breast/ovarian cancer families.

BACKGROUND: Breast cancer is the leading cause of cancer death in women in Algeria. The contribution of BRCA1 and BRCA2 mutations to hereditary breast/ovarian cancer in Algerian population is largely unknown. Here, we describe analysis of BRCA1 and BRCA2 genes in 86 individuals from 70 families from an Algerian cohort with a personal and family history suggestive of genetic predisposition to breast cancer. METHODS: The approach used is based on BRCA1 and BRCA2 mutations screening by High-Resolution Melting (HRM) curve analysis followed by direct sequencing. All samples for which no pathogenic mutation was found were analyzed by MLPA for large deletions or duplications. RESULTS: Three distinct pathogenic mutations c.83_84delTG, c.181T>G, c.798_799delTT and two large rearrangements involving deletion of exon 2 and exon 8 respectively, were detected in BRCA1 gene. Moreover 17 unclassified variants and polymorphisms were detected in BRCA1 gene (6 described for the first time). Two pathogenic mutations, c.1310_1313delAAGA and c.5722_5723delCT and 40 unclassified variants and polymorphisms (14 never described before) were identified in BRCA2 gene. CONCLUSIONS: For the first time, we used HRM and MLPA to identify BRCA1 and BRCA2 mutations in Algerian patients with a personal and family history suggestive of genetic predisposition to breast cancer. The implications of these new findings in regard to genetic testing and counseling are substantial for the Algerian population.