Haemochromatosis gene (HFE) mutations in viral-associated neoplasia: Linkage to cervical cancer.
The present study examines the frequency of the two main HFE mutations (C282Y and H63D) in a randomly selected population of 346 individuals including 201 DNA samples from women with cervical neoplasia (including high-grade squamous intraepithelial lesions and invasive squamous cell carcinoma) and a control population of 146 women from the same geographical area. We found a significantly lower risk of development of cervical neoplasia in H63D carriers (OR = 0.56; 95% CI 0.35-0.92; p = 0.01). Multivariate logistic regression analysis confirms this observation (OR = 0.55; 95% CI 0.35-0.88, p = 0.01). Regarding the C282Y mutation no association was found (OR = 1.32; 95% CI 0.53-3.33; p = 0.52). In addition, a significant difference between H63D carrier and non-carrier women on the time-to-onset of cervical lesions was observed (log-rank test: p = 0.0012). These results indicate that HFE could be considered a candidate modifier gene of viral-related neoplasia such as cervical carcinoma possibly by a dual role on iron metabolism and immunological system.
Cardoso
Carla S
CS
Institute for Molecular and Cell Biology (IBMC), Iron Genes and Immune System (IRIS), Porto, Portugal.
Araújo
Hélder C
HC
Cruz
Eugénia
E
Afonso
Ana
A
Mascarenhas
Cláudia
C
Almeida
Susana
S
Moutinho
José
J
Lopes
Carlos
C
Medeiros
Rui
R
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002874:Chromosome Mapping; D015897:Comorbidity; D004252:DNA Mutational Analysis; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology / Q000235:genetics; D005820:Genetic Testing / Q000379:methods; D014644:Genetic Variation / Q000235:genetics; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006801:Humans; D015994:Incidence; D015810:Linkage Disequilibrium; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D030361:Papillomavirus Infections / Q000453:epidemiology* / Q000235:genetics*; D011174:Portugal / Q000453:epidemiology; D018570:Risk Assessment / Q000379:methods; D002583:Uterine Cervical Neoplasms / Q000453:epidemiology* / Q000235:genetics*; D002578:Uterine Cervical Dysplasia / Q000453:epidemiology* / Q000235:genetics*
C103673:HFE protein, human; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins