Dataset Information

FEN1 gene variants confer reduced risk of breast cancer in chinese women: A case-control study.

ABSTRACT: This study aimed to assess the associations of two common Flap endonuclease 1 (FEN1) polymorphisms (rs4246215 and rs174538) with breast cancer risk in northwest Chinese women. We conducted a case-control study with 560 breast cancer patients and 583 age-matched healthy controls from Northwest China. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were used to estimate the associations. We found a significantly reduced risk of breast cancer associated with T allele of rs4246215 (allele model: OR 0.81, 95% CI 0.68-0.96; homozygote model: OR = 0.59, 95% CI = 0.40-0.87; recessive model: OR = 0.61, 95% CI = 0.42-0.89), especially in postmenopausal women (OR = 0.58, 95% CI = 0.35-0.97). Furthermore, the polymorphism showed a decreased association with larger tumor size (heterozygote model: OR = 0.63, 95% CI = 0.44-0.92; dominant model: OR = 0.63, 95% CI = 0.44-0.90). For rs174538, we did not find any difference in all genetic models. However, rs174538 was associated with lymph node metastasis (heterozygote model: OR = 0.57, 95% CI = 0.39-0.81; dominant model: OR = 0.61, 95% CI = 0.43-0.86) and estrogen receptor status (heterozygote model: OR = 1.50, 95% CI = 1.05-2.15; dominant model: OR = 1.42, 95% CI = 1.01-1.98). Haplotype analysis showed that Trs4246215Grs174538 haplotype was a protective factor of breast cancer (OR = 0.34, 95% CI = 0.14-0.81). Our results suggest that FEN1 polymorphisms may reduce the risk of breast cancer in Chinese women.

SUBMITTER: Lin S

PROVIDER: S-EPMC5363647 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature

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FEN1 gene variants confer reduced risk of breast cancer in chinese women: A case-control study.

Lin Shuai S Wang Meng M Liu Xinghan X Lu Ye Y Gong Zhuoqing Z Guo Yan Y Yang Pengtao P Tian Tian T Dai Cong C Zheng Yi Y Xu Peng P Li Shanli S Zhu Yuyao Y Dai Zhijun Z

Oncotarget 20161101 47

This study aimed to assess the associations of two common Flap endonuclease 1 (FEN1) polymorphisms (rs4246215 and rs174538) with breast cancer risk in northwest Chinese women. We conducted a case-control study with 560 breast cancer patients and 583 age-matched healthy controls from Northwest China. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were used to estimate the associations. We found a significantly reduced risk of breast cancer associated with T allele of rs4246215 (allele m ...[more]

PMID: 27801669

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Project description:INTRODUCTION: Recently, several genome-wide association studies (GWAS) have identified novel single nucleotide polymorphisms (SNPs) associated with breast cancer risk. However, most of the studies were conducted among Caucasians and only one from Chinese. METHODS: In the current study, we first tested whether 15 SNPs identified by previous GWAS were also breast cancer marker SNPs in this Chinese population. Then, we grouped the marker SNPs, and modeled them with clinical risk factors, to see the usage of these factors in breast cancer risk assessment. Two methods (risk factors counting and odds ratio (OR) weighted risk scoring) were used to evaluate the cumulative effects of the five significant SNPs and two clinical risk factors (age at menarche and age at first live birth). RESULTS: Five SNPs located at 2q35, 3p24, 6q22, 6q25 and 10q26 were consistently associated with breast cancer risk in both testing set (878 cases and 900 controls) and validation set (914 cases and 967 controls) samples. Overall, all of the five SNPs contributed to breast cancer susceptibility in a dominant genetic model (2q35, rs13387042: adjusted OR = 1.26, P = 0.006; 3q24.1, rs2307032: adjusted OR = 1.24, P = 0.005; 6q22.33, rs2180341: adjusted OR = 1.22, P = 0.006; 6q25.1, rs2046210: adjusted OR = 1.51, P = 2.40 × 10-8; 10q26.13, rs2981582: adjusted OR = 1.31, P = 1.96 × 10-4). Risk score analyses (area under the curve (AUC): 0.649, 95% confidence interval (CI): 0.631 to 0.667; sensitivity = 62.60%, specificity = 57.05%) presented better discrimination than that by risk factors counting (AUC: 0.637, 95% CI: 0.619 to 0.655; sensitivity = 62.16%, specificity = 60.03%) (P < 0.0001). Absolute risk was then calculated by the modified Gail model and an AUC of 0.658 (95% CI = 0.640 to 0.676) (sensitivity = 61.98%, specificity = 60.26%) was obtained for the combination of five marker SNPs, age at menarche and age at first live birth. CONCLUSIONS: This study shows that five GWAS identified variants were also consistently validated in this Chinese population and combining these genetic variants with other risk factors can improve the risk predictive ability of breast cancer. However, more breast cancer associated risk variants should be incorporated to optimize the risk assessment.

Dataset Information

FEN1 gene variants confer reduced risk of breast cancer in chinese women: A case-control study.

Publications

FEN1 gene variants confer reduced risk of breast cancer in chinese women: A case-control study.

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