title: A polymorphism in Werner syndrome gene is associated with breast cancer susceptibility in Chinese women.
abstract: RecQ helicases play a central role in maintaining genome stability and may interact with some important cancer-related proteins such as BRCA1. Mutations of the human RecQ helicase genes WRN and BLM lead to rare autosomal recessive disorders, Werner and Bloom syndromes, which are associated with premature aging and cancer predisposition, including breast cancer. In this case-control study of 1,004 breast cancer cases and 1,008 controls, we tested the hypothesis that non-conservative amino acid exchanges in WRN (leu1074Phe), BLM (Met298Thr) and BRCA1 (Pro871Leu) are independently or jointly associated with the risk of breast cancer in Chinese women. We found that the variant genotype of WRN Leu1074Phe was associated with a 1.36-fold significantly increased risk of breast cancer (OR = 1.36, 95% CI = 1.06-1.74). Moreover, a significant gene-environment interaction was evident between WRN leu1074Phe and age at menarche (P (int) = 0.02). Subjects carrying Phe/Phe genotype and with earlier age at menarche had 3.58-fold increased risk of breast cancer (OR = 3.58, 95% CI = 2.54-5.05). However, we did not find the significant main effect of polymorphisms in BLM and BRCA1 and also no locus-locus interactions were identified between WRN, BLM and BRCA1. These findings indicate that WRN leu1074Phe variant may contribute to the susceptibility of breast cancer in Chinese women.
authors.affiliation: Laboratory of Reproductive Medicine, Nanjing Medical University, 210029, Nanjing, China.
authors.forename: Zhanwei
authors.initials: Z
authors.lastname: Wang
authors.forename: Yan
authors.initials: Y
authors.lastname: Xu
authors.forename: Jinhai
authors.initials: J
authors.lastname: Tang
authors.forename: Hongxia
authors.initials: H
authors.lastname: Ma
authors.forename: Jianwei
authors.initials: J
authors.lastname: Qin
authors.forename: Chen
authors.initials: C
authors.lastname: Lu
authors.forename: Xuechen
authors.initials: X
authors.lastname: Wang
authors.forename: Zhibin
authors.initials: Z
authors.lastname: Hu
authors.forename: Xinru
authors.initials: X
authors.lastname: Wang
authors.forename: Hongbing
authors.initials: H
authors.lastname: Shen
mesh_terms: D000328:Adult; D000368:Aged; D019943:Amino Acid Substitution; D001943:Breast Neoplasms / Q000737:chemistry / Q000453:epidemiology / Q000235:genetics*; D016022:Case-Control Studies; D002681:China / Q000453:epidemiology; D005090:Exodeoxyribonucleases / Q000235:genetics* / Q000502:physiology; D005260:Female; D019398:Genes, BRCA1; D052138:Genes, Neoplasm; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008572:Menarche / Q000235:genetics*; D008593:Menopause; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000032:analysis / Q000235:genetics* / Q000502:physiology; D020641:Polymorphism, Single Nucleotide; D053484:RecQ Helicases / Q000235:genetics* / Q000502:physiology; D011960:Receptors, Estrogen / Q000032:analysis; D011980:Receptors, Progesterone / Q000032:analysis; D012306:Risk; D014898:Werner Syndrome / Q000235:genetics*; D000071657:Werner Syndrome Helicase
chemical_list: D009363:Neoplasm Proteins; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D005090:Exodeoxyribonucleases; C097151:Bloom syndrome protein; D053484:RecQ Helicases; C098785:WRN protein, human; D000071657:Werner Syndrome Helicase