BACKGROUND: Single nucleotide polymorphisms (SNPs) in nucleotide excision repair (NER) pathway genes may modulate DNA repair capacity and increase susceptibility to breast cancer (BC). A case-control study was conducted by evaluating genes involved in DNA repair to identify polymorphisms associated with BC. METHODS: The 384 SNPs of 38 candidate genes were genotyped using the Illumina GoldenGate method. Genotypes were determined in a case-control study that consisted of 346 BC patients and 361 controls. Odds ratios and 95% confidence intervals were computed using logistic regression models. Multiple logistic regression models adjusted for age, family history of BC, and body mass index were used. RESULTS: Gene-gene interaction analysis among the DNA repair pathway genes showed significant effects on BC risk. ERCC2 rs50872 (TC genotype) in combination with XPA rs2808668 (TC genotype) and rs1800975 (AG genotype) was strongly associated with an increased risk of BC (P = .0004 and .0002, P(Bonferroni) = .023 and .014, respectively). Moreover, the T-G (including rs2808668 and rs1800975) haplotype in XPA combined with the ERCC2 T allele in rs50872 carriers was also associated with additive risk effect of BC (odds ratios: 2.58, 2.62, and 3.49, respectively). CONCLUSION: Genetic variation in DNA repair genes involved in NER mechanisms increased the risk of BC development. These results suggested that a stronger combined effect of SNPs via gene-gene interaction may help to predict BC risk.
BACKGROUND: Single nucleotide polymorphisms (SNPs) in nucleotide excision repair (NER) pathway genes may modulate DNA repair capacity and increase susceptibility to breast cancer (BC). A case-control study was conducted by evaluating genes involved in DNA repair to identify polymorphisms associated with BC. METHODS: The 384 SNPs of 38 candidate genes were genotyped using the Illumina GoldenGate method. Genotypes were determined in a case-control study that consisted of 346 BC patients and 361 controls. Odds ratios and 95% confidence intervals were computed using logistic regression models. Multiple logistic regression models adjusted for age, family history of BC, and body mass index were used. RESULTS: Gene-gene interaction analysis among the DNA repair pathway genes showed significant effects on BC risk. ERCC2rs50872 (TC genotype) in combination with XPA rs2808668 (TC genotype) and rs1800975 (AG genotype) was strongly associated with an increased risk of BC (P = .0004 and .0002, P(Bonferroni) = .023 and .014, respectively). Moreover, the T-G (including rs2808668 and rs1800975) haplotype in XPA combined with the ERCC2 T allele in rs50872 carriers was also associated with additive risk effect of BC (odds ratios: 2.58, 2.62, and 3.49, respectively). CONCLUSION: Genetic variation in DNA repair genes involved in NER mechanisms increased the risk of BC development. These results suggested that a stronger combined effect of SNPs via gene-gene interaction may help to predict BC risk.
Authors: Yuan Lin; Harvind S Chahal; Wenting Wu; Hyunje G Cho; Katherine J Ransohoff; Fengju Song; Jean Y Tang; Kavita Y Sarin; Jiali Han Journal: Int J Cancer Date: 2017-05-31 Impact factor: 7.396
Authors: Luís S Santos; Susana N Silva; Octávia M Gil; Teresa C Ferreira; Edward Limbert; José Rueff Journal: Oncol Lett Date: 2018-02-21 Impact factor: 2.967
Authors: Molly A Hall; John Wallace; Anastasia M Lucas; Yuki Bradford; Shefali S Verma; Bertram Müller-Myhsok; Kristin Passero; Jiayan Zhou; John McGuigan; Beibei Jiang; Sarah A Pendergrass; Yanfei Zhang; Peggy Peissig; Murray Brilliant; Patrick Sleiman; Hakon Hakonarson; John B Harley; Krzysztof Kiryluk; Kristel Van Steen; Jason H Moore; Marylyn D Ritchie Journal: PLoS Genet Date: 2021-06-04 Impact factor: 5.917