Male and female breast cancer: the two faces of the same genetic susceptibility coin.

BACKGROUND: Breast cancer (BC) is the most common cancer in women. In contrast, male BC is about 100 times less common than in women, being considered a rare disease. Male BC may be a distinctive subtype of BC and available data seems to indicate that male BC has a higher dependence on genetic variants than female BC. Nevertheless, the same prognostic and predictive markers are used to determine optimal management strategies for both male and female BC. Several studies have assessed the role of genetic polymorphisms (SNPs) in DNA repair genes in female BC susceptibility. However, data on male BC is scarce. Thus, the current study aimed to assess the role of SNPs in XRCC1, MUTYH and TP53 genes in a male cohort of BC, and, in addition, compare the male data with matched results previously genotyped in female BC patients. METHODS: The male BC cohort was genotyped through Real-Time PCR using TaqMan Assays for several SNPs previously analysed in Portuguese female BC patients. RESULTS: The results obtained indicate significant differences in BC susceptibility between males and females for the XRCC1 rs1799782, MUTYH rs3219489 and TP53 rs1042522 and rs8064946 variants. CONCLUSIONS: In males, XRCC1 and TP53 variants, when in heterozygosity, seem to be related with lower susceptibility for BC, contrasting with higher susceptibility for a MUTYH variant in females. These findings may help to explain the difference in incidence of BC between the two sexes.

Special Issue: Genetic Perspectives in Thyroid Cancer.

Thyroid cancer is not just a common type of cancer, it is the most frequently diagnosed endocrine malignancy worldwide [...].

Genetic Basis of Nonsyndromic Sensorineural Hearing Loss in the Sub-Saharan African Island Population of São Tomé and Príncipe: The Role of the DFNB1 Locus?

Hearing loss (HL) is a common condition with both genetic and environmental causes, and it greatly impacts global health. The prevalence of HL is reportedly higher in developing countries such as the Sub-Saharan African island of São Tomé and Príncipe, where the deaf community is estimated to be less than 1% of the population. We investigated the role of the DFNB1 locus (GJB2 and GJB6 genes) in the etiology of nonsyndromic sensorineural hearing loss (NSSHL) in São Tomé and Príncipe. A sample of 316 individuals, comprising 136 NSSHL patients (92 bilateral, 44 unilateral) and 180 controls, underwent a clinical and audiological examination. Sequencing of the GJB2 coding region and testing for the (GJB6-D13S1830) and del(GJB6-D13S1854) GJB6 deletions were performed. A total of 311 out of 316 individuals were successfully analyzed regarding the GJB2 and GJB6 genetic variations, respectively. The frequency of the GJB2 coding mutations in patients and controls was low. Some of those coding mutations are the most commonly found in Eurasian and Mediterranean populations and have also been identified in Portugal. None of the GJB6 deletions was present. The presence of certain coding variants in São Tomé and Príncipe suggests a non-Sub-Saharan genetic influx and supports the previously reported genetic influx from European (mainly Portuguese) ancestors. In summary, DFNB1 locus does not appear to be a major contributor to NSSHL in São Tomé and Príncipe. However, the presence of both pathogenic and likely pathogenic mutations in GJB2 suggests that GJB2-related NSSHL might still occur in this population, warranting further research on GJB2 testing in NSSHL cases.

The role of common variants of non-homologous end-joining repair genes XRCC4, LIG4 and Ku80 in thyroid cancer risk.

Variations, such as single nucleotide polymorphisms (SNPs) in DNA damage repair genes have been pointed out as possible factors to cancer predisposition. Ionizing radiation (IR) induces DNA double strand breaks (DSBs) and is the main recognized risk factor for thyroid cancer. However, most of the patients do not show chronic contact with IR and the other factors have non-concordant data. Thus, thyroid cancer could be due to gene variations in association with certain exogenous factors. One of the pathways that repair DSBs is DNA non-homologous end-joining (NHEJ) that comprises several polymorphic genes. We intend to study the role of polymorphic variants in XRCC4, LIG4 and Ku80 genes, since there is scarcity of data on the role of these genes in thyroid cancer susceptibility. We carried out a hospital-based case-control study in a Caucasian Portuguese population (109 patients and 217 controls) to estimate the potential role of the XRCC4 (N298S and T134I), LIG4 (T9I) and Ku80 (Ex21-238Gright curved arrow A, Ex21+338Tright curved arrow C, Ex21-352Cright curved arrow A, Ex21+466Aright curved arrow G) polymorphisms in the individual susceptibility for this disease. The results here reported do not associate these polymorphisms with susceptibility for non-familial thyroid cancer. However, when the data were analyzed according to the type of tumour, significant results for Ku80 Ex21-238Gright curved arrow A and Ex21+466Aright curved arrow G were found for papillary tumours (adjusted OR = 2.281; 95% CI =; 1.063-4.894; P=0.034). Taken together these results suggest that some of these variants in NHEJ genes can contribute to thyroid cancer susceptibility. However, further studies with a larger sample size will be needed to support our results.