Polymorphisms in oxidative stress‐related genes and postmenopausal breast cancer risk

• Published in: International journal of cancer Vol. 129; no. 6; pp. 1467 - 1476
• Main Authors: Seibold, Petra, Hein, Rebecca, Schmezer, Peter, Hall, Per, Liu, Jianjun, Dahmen, Norbert, Flesch‐Janys, Dieter, Popanda, Odilia, Chang‐Claude, Jenny
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 15.09.2011; Wiley-Blackwell
• Subjects: antioxidant defense enzymes; Biological and medical sciences; Breast cancer; Breast Neoplasms - genetics; Breast Neoplasms - metabolism; Cancer; Carcinogenesis; case‐control study; Female; genetic polymorphisms; Genetic Predisposition to Disease; genetic susceptibility; Gynecology. Andrology. Obstetrics; hormone replacement therapy; Humans; joint analysis; Mammary gland diseases; Medical sciences; Metallothioneins; Middle Aged; Oxidative stress; Oxidative Stress - genetics; Oxygen; Polymorphism, Single Nucleotide; Post-menopause; Postmenopause; Risk Assessment; Risk factors; thioredoxin; Tumors; Europe; Germany; Oxidative stress; Breast disease; Genetic variability; Case control study; Thioredoxin; Epidemiology; Cancerology; Gene; case-control study; Postmenopause; Genetics; genetic susceptibility; Public health; Human; Genotype; Breast cancer; Malignant tumor; genetic polymorphisms; antioxidant defense enzymes; Mammary gland diseases; Risk factor; Single nucleotide polymorphism; Metallothionein; joint analysis; Cancer
• ISSN: 0020-7136; 1097-0215; 1097-0215
• DOI: 10.1002/ijc.25761

Breast cancer is the most frequent cancer type among women in western countries. In addition to established risk factors like hormone replacement therapy, oxidative stress may play a role in carcinogenesis through an unbalanced generation of reactive oxygen species that leads to genetic instability. The aim of this study is to assess the influence of common single nucleotide polymorphisms (SNPs) in candidate genes related to oxidative stress on postmenopausal breast cancer risk. We genotyped 109 polymorphisms (mainly tagging SNPs) in 22 candidate genes in 1,639 postmenopausal breast cancer cases and 1,967 controls (set 1) from the German population‐based case‐control study “MARIE”. SNPs showing association in set 1 were tested in further 863 cases and 2,863 controls from MARIE (set 2) using a joint analysis strategy. Six polymorphisms evaluated in the combined set showed significantly modified breast cancer risk per allele in the joint analysis, including SNPs in CYBA (encoding a subunit of the NADPH oxidase: rs3794624), MT2A (metallothionein 2A: rs1580833), TXN (thioredoxin: rs2301241), and in TXN2 (thioredoxin 2: rs2267337, rs2281082, rs4821494). Associations with the CYBA rs3794624 (OR per allele: 0.93, 95% CI 0.87–0.99) and TXN rs2301241 variants (OR per allele: 1.05, 95% CI 1.00–1.10) were confirmed in the summary risk estimate analysis using up to three additional studies. We found some evidence for association of polymorphisms in genes of the thioredoxin system, CYBA, and MT2A with postmenopausal breast cancer risk. Summary evidence including independent datasets indicated moderate effects in CYBA and TXN that warrant confirmation in large independent studies.