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

Abstract

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.

Risk of developing a second primary cancer in male breast cancer survivors: a systematic review and meta-analysis

“…Research in this area has been undertaken for contralateral BC in women [52], but is otherwise very scarce. There is some evidence that a higher proportion of male than female BC cases are due to pathogenic variants in BC susceptibility genes [53,54], with the largest study of germline susceptibility in male BC cases finding 13.7% of male BC survivors to carry such variants [37]. Pathogenic germline variants in BC susceptibility genes could account for a sizeable proportion of second primaries following male BC, with a recent large study confirming non-breast primaries to be 58% more common among male carriers of deleterious BRCA1/2 variants than among male relatives of carriers who were either untested for, or confirmed not to carry, such a variant [35].…”

Genetic determinants and absence of breast cancer in Xavante Indians in Sangradouro Reserve, Brazil

“…This study concerns and is centered on female Xavante Indians. Since there are grounds to believe that male breast cancer may display different genetic determinants 38 , the data presented applies solely to female breast cancer.…”

BRCA1 VUS: A functional analysis to differentiate pathogenic from benign variants identified in clinical diagnostic panels for breast cancer

“…Thus, BRCA1 acts as a tumor suppressor. Mutations in BRCA1 have long been associated with increased risk of breast cancer in men and women, as well as several other types of cancer and increased DSB, indicating a defect in DNA repair ( 36 ). To date, there is no evidence of cell-type specific differences in the activity of DSB repair pathways and in other BRCA1-specific interactions.…”

“…The increasingly common application of NGS has identified a number of variants in genes suspected to be involved in cancer predisposition, in particular for breast cancer. Several of these genes are associated with DNA repair and have been reported in female and male breast cancer patients ( 36 ). However, the increased identification of variants of high penetrant genes through NGS has led to considerable difficulties in the adequate classification of their pathogenicity.…”