CYP17, GSTP1, PON1 and GLO1 gene polymorphisms as risk factors for breast cancer: an Italian case-control study.
BACKGROUND
Estrogens, environmental chemicals with carcinogenic potential, as well as oxidative and carbonyl stresses play a very important role in breast cancer (BC) genesis and progression. Therefore, polymorphisms of genes encoding enzymes involved in estrogen biosynthesis pathway and in the metabolic activation of pro-carcinogens to genotoxic intermediates, such as cytochrome P450C17alpha (CYP17), endogenous free-radical scavenging systems, such as glutathione S-transferase (GSTP1) and paraoxonase 1 (PON1), and anti-glycation defenses, such as glyoxalase I (GLO1), could influence individual susceptibility to BC. In the present case-control study, we investigated the possible association of CYP17 A1A2, GSTP1 ILE105VAL, PON1 Q192R or L55M, and GLO1 A111E polymorphisms with the risk of BC.


METHODS
The above-said five polymorphisms were characterized in 547 patients with BC and in 544 healthy controls by PCR/RFLP methods, using DNA from whole blood. To estimate the relative risks, Odds ratios and 95% confidence intervals were calculated using unconditional logistic regression after adjusting for the known risk factors for BC.


RESULTS
CYP17 polymorphism had no major effect in BC proneness in the overall population. However, it modified the risk of BC for certain subgroups of patients. In particular, among premenopausal women with the A1A1 genotype, a protective effect of later age at menarche and parity was observed. As to GSTP1 and PON1 192 polymorphisms, the mutant Val and R alleles, respectively, were associated with a decreased risk of developing BC, while polymorphisms in PON1 55 and GLO1 were associated with an increased risk of this neoplasia. However, these findings, while nominally significant, did not withstand correction for multiple testing.


CONCLUSIONS
Genetic polymorphisms in biotransformation enzymes CYP17, GSTP1, PON1 and GLO1 could be associated with the risk for BC. Although significances did not withstand correction for multiple testing, the results of our exploratory analysis warrant further studies on the above mentioned genes and BC.
Antognelli
Cinzia
C
Department of Experimental Medicine, University of Perugia, Perugia, Italy. cinzia.antognelli@unipg.it
Del Buono
Chiara
C
Ludovini
Vienna
V
Gori
Stefania
S
Talesa
Vincenzo N
VN
Crinò
Lucio
L
Barberini
Francesco
F
Rulli
Antonio
A
D000368:Aged; D043303:Aryldialkylphosphatase / Q000235:genetics*; D001943:Breast Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D051549:Glutathione S-Transferase pi / Q000235:genetics*; D006801:Humans; D007558:Italy; D007791:Lactoylglutathione Lyase / Q000235:genetics*; D016015:Logistic Models; D008593:Menopause; D008875:Middle Aged; D009367:Neoplasm Staging; D016017:Odds Ratio; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D012307:Risk Factors; D013254:Steroid 17-alpha-Hydroxylase / Q000235:genetics*; D013997:Time Factors
D013254:Steroid 17-alpha-Hydroxylase; D051549:Glutathione S-Transferase pi; D043303:Aryldialkylphosphatase; C468406:PON1 protein, human; D007791:Lactoylglutathione Lyase