Genome-wide association study identifies a common variant in RAD51B associated with male breast cancer risk

Orr, Nick; Lemnrau, Alina; Cooke, Rosie; Fletcher, Olivia; Tomczyk, Katarzyna; Jones, Michael E.; Johnson, Nichola; Lord, Christopher J.; Mitsopoulos, Costas; Zvelebil, Marketa; McDade, Simon S.; Buck, Gemma; Blancher, Christine; Trainer, Alison H.; James, Paul; Bojesen, Stig E.; Bokmand, Susanne; Nevanlinna, Heli; Mattson, Johanna; Friedman, Eitan; Laitman, Yael; Palli, Domenico; Masala, Giovanna; Zanna, Ines; Ottini, Laura; Giannini, Giuseppe; Hollestelle, Antoinette; Ouweland, Ans M.W. van den; Novaković, Srdjan; Krajc, Mateja; Gago‐Dominguez, Manuela; Castelao, Jose E.; Olsson, Håkan; Hedenfalk, Ingrid; Easton, Douglas F.; Pharoah, Paul D.P.; Dunning, Alison M.; Bishop, D. Timothy; Neuhausen, Susan L.; Steele, Linda; Houlston, Richard S.; García-Closas, Montserrat; Ashworth, Alan; Swerdlow, Anthony

doi:10.1038/ng.2417

Cited by 99 publications

(75 citation statements)

References 15 publications

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“…In particular, rs1314913 was found specifically associated with increased BC risk in men, whereas rs3803662 was found associated with increased BC risk also in women [23]. Furthermore, by gene candidate approach ESR1 locus was found to be associated with BC risk in men, and, in particular, with increased risk in oestrogen receptor (ER) negative MBC cases and in male BRCA1/2 mutation carriers [22,24].…”

Section: Introductionmentioning

confidence: 97%

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Novel and known genetic variants for male breast cancer risk at 8q24.21, 9p21.3, 11q13.3 and 14q24.1: Results from a multicenter study in Italy

Silvestri

Rizzolo

Scarnò³

et al. 2015

European Journal of Cancer

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Section: Introductionmentioning

confidence: 97%

“…By contrast, only a few studies addressed the role of low-penetrance alleles in MBC susceptibility [22][23][24].…”

Section: Introductionmentioning

confidence: 99%

Novel and known genetic variants for male breast cancer risk at 8q24.21, 9p21.3, 11q13.3 and 14q24.1: Results from a multicenter study in Italy

Silvestri

Rizzolo

Scarnò³

et al. 2015

European Journal of Cancer

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“…In Table 4 Distribution of the three SNPs associated with overall MBC risk in the case's series according to ER, PR, and HER2 status, and p values of the association with specific MBC subtypes ER PR HER2 particular, ESR1 and TOX3 showed the strongest association. Notably, we recently reported a strong association for TOX3 and ESR1 with increased MBC risk in a large collaborative series [23]. In particular, TOX3 reached a genome wide-significance and showed an association stronger in males than that in females, while ESR1 was validated in the same series [22,23].…”

Section: Discussionmentioning

confidence: 91%

“…Notably, we recently reported a strong association for TOX3 and ESR1 with increased MBC risk in a large collaborative series [23]. In particular, TOX3 reached a genome wide-significance and showed an association stronger in males than that in females, while ESR1 was validated in the same series [22,23]. In contrast, FGFR2 did not emerge in such analysis.…”

Section: Discussionmentioning

confidence: 92%

“…Genome-wide association studies (GWAS) have identified associations between single nucleotide polymorphisms (SNPs), acting as common lowpenetrance variant alleles, and BC risk in women [13][14][15][16][17][18][19][20][21]. An involvement of some of the SNPs found to be associated with FBC has been suggested in MBC susceptibility [22], and by GWAS we could recently identify a novel common variant associated with MBC [23].…”

Section: Introductionmentioning

confidence: 99%

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Association of low-penetrance alleles with male breast cancer risk and clinicopathological characteristics: results from a multicenter study in Italy

Ottini

Silvestri

Saieva

et al. 2013

Breast Cancer Res Treat

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It is well-known that male breast cancer (MBC) susceptibility is mainly due to high-penetrance BRCA1/2 mutations. Here, we investigated whether common lowpenetrance breast cancer (BC) susceptibility alleles may influence MBC risk in Italian population and whether variant alleles may be associated with specific clinicopathological features of MBCs. In the frame of the Italian Multicenter Study on MBC, we genotyped 413 MBCs and 745 agematched male controls at 9 SNPs annotating known BC susceptibility loci. By multivariate logistic regression models, we found a significant increased MBC risk for 3 SNPs, in particular, with codominant models, for rs2046210/ESR1 (OR = 1.71; 95 % CI: 1.43-2.05; p = 0.0001), rs3803662/ TOX3 (OR = 1.59; 95 % CI: 1.32-1.92; p = 0.0001), and rs2981582/FGFR2 (OR = 1.26; 95 % CI: 1.05-1.50; p = 0.013). Furthermore, we showed that the prevalence of the risk genotypes of ESR1 tended to be higher in ERtumors (p = 0.062). In a case-case multivariate analysis, a statistically significant association between ESR1 and ERtumors was found (OR = 1.88; 95 % CI: 1.03-3.49; p = 0.039). Overall, our data, based on a large and wellcharacterized MBC series, support the hypothesis that common low-penetrance BC susceptibility alleles play a role in MBC susceptibility and, interestingly, indicate that ESR1 is associated with a distinct tumor subtype defined by ER-negative status.

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Genetic variants within microRNA‐binding site of RAD51B are associated with risk of cervical cancer in Chinese women

et al. 2016

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RAD51B plays a central role in homologous recombinational repair (HRR) of DNA double‐strand breaks (DSBs), which is important to prevent genomic instability, a hallmark of cancer. Recent studies suggested that common genetic variants of RAD51B may contribute to cancer susceptibility. In this study, we aimed to investigate whether potentially functional variants within miRNA‐binding sites of RAD51B are associated with risk of cervical cancer. A total of 1486 cervical cancer patients and 1536 cancer‐free controls were enrolled, and two genetic variants, rs963917 (A > G) and rs963918 (T > C), were genotyped in all participants. Using multivariate logistic regression analyses, we found that G allele of rs963917 conferred lower risk of cervical cancer compared to A allele (adjusted OR = 0.89, 95% CI = 0.80–0.99, P = 0.039). Similarly, rs963918 allele C was associated with a decreased risk for cervical cancer compared with allele T (adjusted OR = 0.84, 95% CI = 0.74–0.94, P = 0.004). Haplotype analyses showed that haplotype GC was also correlated with lower risk (OR = 0.83, 95% CI = 0.73–0.95, P = 0.005) compared with the most common haplotype AT. In summary, our study suggested that miRNA‐binding site genetic variants of RAD51B may modify the susceptibility to cervical cancer, which is important to identify individuals with differential risk for this malignancy and to improve the effectiveness of preventive intervention.

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Genome-wide association study identifies a common variant in RAD51B associated with male breast cancer risk

Cited by 99 publications

References 15 publications

Novel and known genetic variants for male breast cancer risk at 8q24.21, 9p21.3, 11q13.3 and 14q24.1: Results from a multicenter study in Italy

Novel and known genetic variants for male breast cancer risk at 8q24.21, 9p21.3, 11q13.3 and 14q24.1: Results from a multicenter study in Italy

Association of low-penetrance alleles with male breast cancer risk and clinicopathological characteristics: results from a multicenter study in Italy

Genetic variants within microRNA‐binding site of RAD51B are associated with risk of cervical cancer in Chinese women

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