Mismatch Repair Polymorphisms as Markers of Breast Cancer Prevalence in the Breast Cancer Family Registry

Abstract

Background Major breast cancer susceptibility genes involved in DNA repair, including BRCA1 and BRCA2, have been identified. However, mutations in these genes account for only 5–10% of identified breast cancer cases. Additional DNA repair pathway genes may also contribute to susceptibility. Materials and Methods We investigated the association between 12 single nucleotide polymorphisms (SNPs) in mismatch repair (MMR) genes and breast cancer risk among 313 sister-sets enrolled in the New York site of the Breast Cancer Family Registry (BCFR) (n=744) using conditional logistic regression analysis. Results An increase in breast cancer risk was observed for women with the MUTYH_rs3219489 variant allele (odds ratio (OR)=2.23, 95% confidence interval (CI)=1.10–4.52) and for women with the MSH2_rs2303428 variant allele (OR=1.73, 95% CI=1.00–2.99). Conclusion Deficiencies in DNA repair pathways, such as MMR, have implications for the onset of familial breast cancer.

Micronuclei Formation upon Radioiodine Therapy for Well-Differentiated Thyroid Cancer: The Influence of DNA Repair Genes Variants

“…MSH4 rs5745325 (c.289G>A; Ala97Thr) has only seldom been evaluated: on single SNP analysis, two prior studies by our team failed to detect an association with either thyroid [21] or breast cancer risk [120]. The same was observed in the only two other association studies that we found focusing on this SNP [121,122]. Interestingly, in three out of these four studies, significant associations were detected when interactions with other SNPs-MSH6 rs1042821 [21], MLH3 rs175080 [120], and CHRNA5 rs16969968 [121]-were considered.…”

Establishment and Characterization of gc-006-03, a Novel Human Signet Ring Cell Gastric Cancer Cell Line Derived from Metastatic Ascites

“…MUTYH , as a base excision gene, plays an important role in many cancers and loss of MUTYH function in human cells could lead to accumulation of oxidative damage and genetic instability 52 . Many studies have revealed the relationship between MUTYH Gln338His polymorphisms (rs3219489) and the risk of many cancers, such as breast cancer 53 , esophageal adenocarcinoma 54 and colorectal cancer 55 . Thus, these mutations in gc-006-03 also reveal its potential for further biological research.…”

Non-BRCA1/2 Breast Cancer Susceptibility Genes: A New Frontier with Clinical Consequences for Plastic Surgeons

“… 1 With reports of breast cancer risk near 18% by age 70 in MLH1 mutation carriers, breast cancer susceptibility has been suspected but not definitively established with these mismatch repair genes as population-based studies remain inconclusive. 1 , 26 , 29 , 30 Genetic instability has also been identified in breast cancer samples from patients with Lynch syndrome. 8 Annual screening surveillance with mammography and MRI has been suggested in this population.…”

“…Monoallelic mutations in the moderately penetrant ataxia telangiectasia mutated (ATM) gene, which helps initiate and suspend cell division during DNA repair, have been associated with various types of cancer including breast and pancreatic cancer. 1 , 4 , 8 , 12 , 25 , 38 , 44 Roughly 2% of the Caucasian population in the United States carries a germline mutation in ATM. 1 Biallelic carriers develop the ataxia-telangiectasia disorder, which is inherited in an autosomal recessive pattern.…”