Interaction between glutathione-S-transferase polymorphisms, smoking habit, and HPV infection in cervical cancer risk.
OBJECTIVE
Human papillomavirus (HPV) infection is considered the major cause of cervical cancer (CC), but a number of infected women do not develop invasive lesions, suggesting the role of genetic susceptibility and environmental co-factors for cancer outbreak. The aim of this study was to investigate whether some GST polymorphisms could influence the risk to develop CC, either by themselves or in combination with smoking habit, in a cohort of high-risk HPV (HR-HPV) infected Italian women.


METHODS
The study population comprises 192 Italian women including 81 HR-HPV infected women bearing cervical lesions and 111 healthy controls. The cases include: 26 low-grade squamous intraepithelial lesions (LSILs), 30 high-grade-SIL, and 25 CCs, while controls were all negative for HPV. DNA was extracted from peripheral blood samples or cytobrush and individuals were genotyped for GSTM1, GSTT1, and GSTP1 polymorphisms using PCR and PCR/RFLP techniques.


RESULTS
On studying the association of GSTs gene polymorphisms with cervical cancer lesions, the combination of GSTM1 null, GSTT1 null and GSTP1 AA genotypes, independently on smoking habit, seems to be related to a 5.7-fold increased risk of developing CLs with a considerable statistical significance (P = 0.0091).


CONCLUSIONS
We suggest that the investigation of multiple gene polymorphisms, versus single genes, could contribute to a better understanding of the effect of susceptibility genes on cancer risk.
Palma
Selena
S
Section Toxicology and Biomedical Sciences, C.R. ENEA Casaccia, Via Anguillarese 301, 00123 Rome, Italy.
Novelli
Flavia
F
Padua
Luca
L
Venuti
Aldo
A
Prignano
Grazia
G
Mariani
Luciano
L
Cozzi
Renata
R
Tirindelli
Donatella
D
Testa
Antonella
A
D000328:Adult; D000368:Aged; D015331:Cohort Studies; D005260:Female; D005838:Genotype; D051549:Glutathione S-Transferase pi / Q000235:genetics* / Q000378:metabolism; D005982:Glutathione Transferase / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008875:Middle Aged; D030361:Papillomavirus Infections / Q000150:complications*; D011110:Polymorphism, Genetic / Q000235:genetics*; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects*; D002583:Uterine Cervical Neoplasms / Q000201:enzymology / Q000209:etiology / Q000821:virology; D055815:Young Adult
D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase; C413545:glutathione S-transferase T1; C496556:GSTP1 protein, human