Related Experiment Videos
MnSOD gene polymorphism association with steroid-dependent cancer
Claudia Giuliano Bica1, Leonardo Leiria de Moura da Silva, Nadima Vieira Toscani
1Fundação Faculdade Federal de Ciências Médicas de Porto Alegre, Rua Sarmento Leite 245, Porto Alegre, RS, 90050-170, Brazil, bicaclaudia@hotmail.com.
Pathology Oncology Research : POR
|June 17, 2008
Summary
The Manganese superoxide dismutase (MnSOD) Val16Ala polymorphism, linked to oxidative stress, may increase breast and prostate cancer risk. The Ala/Ala genotype showed elevated risk in both male and female breast cancer patients and prostate cancer patients.
Area of Science:
- Genetics and Oncology
- Molecular Biology
- Cancer Research
Background:
- Oxidative stress and DNA damage are implicated in carcinogenesis.
- The Manganese superoxide dismutase (MnSOD) Val16Ala polymorphism is a potential genetic risk factor for breast and prostate cancer.
- The role of oxidative stress in male breast cancer is understudied due to its rarity.
Purpose of the Study:
- To investigate the association between the MnSOD Val16Ala polymorphism and the risk of prostate cancer (PC), male breast cancer (MBC), and female breast cancer (FBC).
- To explore the role of oxidative stress in male breast cancer etiology.
Main Methods:
- A case-control study was conducted involving 11 MBC, 51 PC, 89 FBC cases, and 372 healthy controls.
- Genotyping for the MnSOD Val16Ala polymorphism was performed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) on blood and tumor samples.
- Statistical analysis included Chi-square or Fisher's test to compare genotype frequencies.
Main Results:
- Observed genotypic frequencies were AA (9.6%), VV (25.4%), and AV (64%), all in Hardy-Weinberg equilibrium.
- The Ala/Ala genotype was associated with an elevated risk of breast and prostate cancer (Odds Ratio = 2.5, p = 0.006).
- This study provides initial evidence linking the MnSOD genetic polymorphism to an increased risk of male breast cancer.
Conclusions:
- The MnSOD Val16Ala polymorphism, particularly the Ala/Ala genotype, is associated with an increased risk of breast cancer in both males and females, and prostate cancer.
- These findings support the hypothesis that MnSOD and oxidative stress play a significant role in the development of these cancers.
- Further research with larger sample sizes is warranted to confirm these associations, especially for male breast cancer.
Related Concept Videos
01:11Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase
Genetic polymorphisms in drug targets have emerged as critical determinants of interindividual variability in drug response and toxicity. Pharmacogenomic investigations increasingly focus on identifying these variations to personalize and optimize therapeutic interventions. A drug target may be a receptor, enzyme, or signaling protein involved in pharmacologic responses or disease-related pathways. While early pharmacogenetic studies focused primarily on drug metabolism, current research...
01:29Pharmacogenetic Phenotypes: Alterations in Pharmacokinetics, Drug Targets and Biologic Milieu
Genetic variations significantly influence drug response through pharmacokinetics, receptor interactions, and biologic milieu modifications. Pharmacokinetic alterations impact drug metabolism and clearance, affecting efficacy and toxicity. Variants in drug-metabolizing enzymes, such as CYP2C9 and CYP2C19, alter drug activation and elimination. For example, CYP2C9 loss-of-function variants require lower warfarin doses to prevent excessive bleeding, while CYP2C19 variants reduce clopidogrel...
02:23Abnormal Proliferation
Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...
01:16Pharmacogenetics of Drug Transporters: P-Glycoprotein and Solute Carrier Transporters
The pharmacogenetics of drug transporters is increasingly recognized as a critical factor influencing interindividual variability in drug absorption, distribution, and elimination. These membrane-bound proteins regulate drugs' movement across cellular barriers by actively pumping them out (efflux) or facilitating their uptake (influx). Among the major transporter families, ATP-binding cassette (ABC) and solute carrier (SLC) transporters play particularly prominent roles. Genetic polymorphisms...
01:33Pleiotropy
Pleiotropy is the phenomenon in which a single gene impacts multiple, seemingly unrelated phenotypic traits. For example, defects in the SOX10 gene cause Waardenburg Syndrome Type 4, or WS4, which can cause defects in pigmentation, hearing impairments, and an absence of intestinal contractions necessary for elimination. This diversity of phenotypes results from the expression pattern of SOX10 in early embryonic and fetal development. SOX10 is found in neural crest cells that form melanocytes,...
01:05Single Nucleotide Polymorphisms-SNPs
A single nucleotide polymorphism or SNP is a single nucleotide variation at a specific genomic position in a large population. It is the most prevalent type of sequence variation found in the human genome. Point mutations that occur in more than 1% of the population qualify as SNPs. These are present once every 1000 nucleotides on an average in the human genome. Replacement of a purine with another purine (A/G) or a pyrimidine with another pyrimidine (C/T) is known as a transition. In contrast,...