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Single-nucleotide polymorphisms in DNA repair genes and association with breast cancer risk in the web study.

ABSTRACT: Base excision repair (BER) and nucleotide excision repair (NER) pathways repair damaged DNA, and polymorphisms in these genes might affect breast cancer susceptibility. We evaluated associations between seven single-nucleotide polymorphisms in four DNA repair genes (ERCC4 rs1799801, XPC rs2227998, rs2228001, rs2228000, OGG1 rs1052133 and XRCC1 rs25487 and rs25486) and breast cancer risk, examining modification by smoking and alcohol consumption, using data from the Western New York Exposures and Breast Cancer Study. Women aged 35-79 years with incident breast cancer (n = 1170) and age- and race-matched controls (n = 2115) were enrolled. Genotyping was performed using matrix-assisted laser desorption ionization time-of-flight mass spectrometry. Unconditional logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CIs). No significant associations were observed in premenopausal women. Among postmenopausal women, rs25487 and rs25486 (OR = 1.24; 95% CI 1.01-1.51 and OR = 1.23; 95% CI 1.01-1.49, respectively, for combined heterozygous and homozygous variant compared with reference) were associated with increased risk of breast cancer. Postmenopausal women carrying the variant allele of the synonymous XPC polymorphism (rs2227998) were also at borderline significantly increased risk (OR = 1.24; 95% CI 1.01-1.52, heterozygous variant compared with reference; OR = 1.22; 95% CI 1.01-1.48, for combined heterozygous and homozygous variant compared with reference). There was no evidence of genotype-smoking and genotype-alcohol consumption interactions for pre- and postmenopausal women. These results indicate that some of the variants in BER and NER genes may influence risk of postmenopausal breast cancer.

SUBMITTER: Roberts MR

PROVIDER: S-EPMC3149207 | biostudies-literature | 2011 Aug

REPOSITORIES: biostudies-literature

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Single-nucleotide polymorphisms in DNA repair genes and association with breast cancer risk in the web study.

Roberts Michelle R MR Shields Peter G PG Ambrosone Christine B CB Nie Jing J Marian Catalin C Krishnan Shiva S SS Goerlitz David S DS Modali Ramakrishna R Seddon Michael M Lehman Teresa T Amend Kandace L KL Trevisan Maurizio M Edge Stephen B SB Freudenheim Jo L JL

Carcinogenesis 20110527 8

Base excision repair (BER) and nucleotide excision repair (NER) pathways repair damaged DNA, and polymorphisms in these genes might affect breast cancer susceptibility. We evaluated associations between seven single-nucleotide polymorphisms in four DNA repair genes (ERCC4 rs1799801, XPC rs2227998, rs2228001, rs2228000, OGG1 rs1052133 and XRCC1 rs25487 and rs25486) and breast cancer risk, examining modification by smoking and alcohol consumption, using data from the Western New York Exposures and ...[more]

PMID: 21622940

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Project description:In this report, we describe a case control study in a Chinese population aimed at identifying possible associations between susceptibility to cervical cancer and single nucleotide polymorphisms in XRCC1 194C>T, XRCC1 280G>A, XRCC1 399G>A, ERCC2 751A>C, ERCC2 156C>A, ERCC1 118C>T, PARP1 762T>C, RAD51 135G>C and HER2 655A>G. The cases comprised 154 patients: 80 cervical squamous cell carcinomas (SCCs), 2 adenocarcinomas and 72 cervical intraepithelial neoplasias (CINs). A total of 177 healthy women were recruited as the controls. A significant association was found between ERCC1 118C>T and SCC in the additive genetic model [odds ratio (OR)=1.711; 95% confidence interval (CI), 1.089-2.880; p=0.021] and the dominant genetic model (OR=1.947; 95% CI, 1.056-3.590; p=0.033). Among women with a smoking family member, ERCC1 118C>T increased SCC risk in the additive model (OR=2.800; 95% CI, 1.314-5.968; p=0.008). For women who had first intercourse before 22 years of age, XRCC1 280G>A was found to act as a protective factor for SCC under the additive model (OR=0.228; 95% CI, 0.058-0.900; p=0.035), while RAD51 135G>C was a risk factor for CIN (OR=4.246; 95% CI, 1.335-13.502; p=0.014). For women who had first intercourse after 22 years of age, the additive genetic model showed RAD51 135G>C (OR=0.359; 95% CI, 0.138-0.934; p=0.036) and HER2 655A>G (OR=0.309; 95% CI, 0.098-0.972; p=0.045) to be protective factors for SCC. XRCC1 399G>A increased CIN risk among women who first gave birth before the age of 22 in the additive genetic model (OR=4.459; 95% CI, 1.139-17.453; p=0.032). For those who first gave birth after age 22, ERCC1 118C>T was found to be a risk factor for SCC in the additive genetic model (OR=1.884; 95% CI, 1.088-3.264; p=0.024). A significant interaction was observed between RAD51 135G>C and age at first intercourse (p(interaction)=0.033 for SCC, p(interaction)=0.021 for CIN), as well with sexual partner number (p(interaction)=0.001 for SCC). The interaction between HER2 655A>G and age at first intercourse, ERCC2 156C>A and family smoking status and XRCC1 280G>A and alcohol consumption were significant, with p(interaction)=0.023 for SCC, p(interaction)=0.021 for CIN and p(interaction)=0.025 for SCC, respectively.

Project description:ObjectiveThe purpose of the present study was to evaluate the associations between seven tagging single nucleotide polymorphisms (tSNPs) and risk of breast cancer assessed by tumor pathological characteristics and body mass index (BMI).MethodsSeven tSNPs of four breast cancer susceptibility genes were analyzed in 734 Chinese women with breast cancer and 672 age-matched healthy controls; then, the association with clinicopathological characteristics, BMI, molecular subtype, TNM (T, tumor; N, lymph node; M, metastasis) staging and lymph node status was determined by unconditional logistic regression.ResultsRs12951053 in TP53 and rs16945628 in BRIP1, displayed increased risk of breast cancer in the BMI ≧ 25 kg/m2 group (OR=1.50, 95% CI: 1.02-2.21, P=0.041 and OR=1.92, 95% CI: 1.13-3.26, P=0.015, respectively). The other five tSNPs (rs1805812, rs2735385 and rs6999227 in NBS1, rs7220719 in BRIP1 and rs2299941 in PTEN) displayed a decreased risk of breast cancer in the 18.5≤BMI<25 kg/m2 group. Rs12951053 in TP53 and rs7220719 in BRIP1 exhibited an increased risk of triple-negative breast cancer (OR=1.50, 95% CI: 1.05-2.15, P=0.026 and OR=2.13, 95% CI: 1.05-4.29, P=0.032, respectively), but three tSNPs in NBS1 (rs1805812, rs2735385 and rs6999227) all displayed a negative association with both luminal B and triple-negative breast cancer. The tSNP rs2299941 in PTEN also exhibited a negative association with each molecular subtype, except triple-negative breast cancer. The majority of tSNPs displayed a negative association with stage II or III breast cancer. Most tSNPs showed a negative association with breast cancer that was lymph node negative or with 1-3 positive nodes. Only rs12951053 in TP53 displayed a positive association with lymph node-negative breast cancer (OR=1.43, 95% CI: 1.08-1.91, P=0.013).ConclusionThe majority of tSNPs displayed a negative association with breast cancer and only a few tSNPs (rs12951053 in TP53, rs16945628 and rs7220719 in BRIP1) showed an increased risk of breast cancer as defined by clinicopathological characteristics.

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Single-nucleotide polymorphisms in DNA repair genes and association with breast cancer risk in the web study.

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Single-nucleotide polymorphisms in DNA repair genes and association with breast cancer risk in the web study.

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