A Molecular Epidemiological Study On The Relationship Between The Interleukin-1 And Susceptibility To Cervical Cancer

Cervical cancer is the second most common cancer among women worldwide after breast cancer,and its high fatality rate seriously imperil the health of people.In the past two decades,there were 500 thousands new cervical cancer cases and 250 thousands cases who died of this cancer around the world every year.Its incidence and mortality are very different in the areas of the same country and in different countries.China is one of the areas with high incidence of cervical cancer.There are about 131.5 thousands new cases every year in our country,accounting for 73%-93%cancer cases in female reproductive system and its mortality is high,being the leading cause of female reproductive system cancer related death.Nowadays the incidence of cervical cancer is continually increasing in China and the new cases are younger than before.The exact etiology of cervical cancer is intricate,though many studies have suggested that environmental and genetic factors may play important roles.Therefore,it is urgent to clarify the mechanism of cervical cancer development and take effective prevention measures.To reach this target, a hospital-based molecular epidemiological study on cervical cancer was conducted in Jiangsu Province.PartⅠAssociation Study between Polymorphisms of Interleukin-1B and Susceptibility to Cervical CancerIL-1B was shown in vitro to regulate a variety of cellular functions in tumor cells.The genetic variants might infuluence the expression level of IL-1β,therefore we hypothysized that IL-1B polymorphisms might be associated with risk of cervival cancer.To test this hypothesis,we conducted a hospital-based case-control study of 374 cervical cancer cases and 408 cancer-free controls in Jiangsu Province,to evaluate the associations of the polymorphisms with cervical cancer risk.We found that the frequencies of IL-1B -31TT,-31TC and -31CC were 30.4%, 46.1%and 23.5%in controls,and 24.9%,50.8%and 24.3%in cervical cancer patients,respectively.Logistic regression analysis revealed that the IL-1B -31TC and -31TC/CC genotypes were significantly associated with increased risks for cervical cancer(adjusted OR=1.45,95% CI=1.02-2.04 and adjusted OR=1.42,95%CI=1.03-1.97,respectively), compared with the -31TT genotype.The IL-1B genotype frequencies of -511CC,-511CT and -511TT were 30.9%,46.3%and 22.8%in controls, and 23.8%,53.5%and 22.7%in cervical cancer patients respectively. Logistic regression analysis revealed that,compared with subjects carting -511CC genotype,those with the -511CT and -511CT/TT genotypes had increased risks of cervical cancer(adjusted OR=1.49,95%CI=1.05-2.01 for -511CT and adjusted OR=1.45,95%CI=1.05-2.01 for-511CT/TT).In the stratification analyses,cervical cancer risk associated with 1L-1B-31TC/CC variant genotypes were more evident in rural women (adjusted OR=1.54,95%CI=1.04-2.28),and in individuals with a later menarche age(adjusted OR=1.64,95%CI=1.05-2.56).And the effect of IL-1B-511CT/TT variant genotypes on cervical cancer were more prominent in postmenopausal women(adjusted OR=1.84,95%CI= 1.16-2.94),in individuals with an early age at first live birth(adjusted OR=2.20,95%CI=1.21-4.01),and in women with more than 2 pregnancies(adjusted OR=1.66,95%CI=1.04-2.64).In these individuals whose plasma IL-1βlevels were more than 38.00pg/ml,the -31C and -511T variant genotypes were associated increased risk for cervical cancer(adjusted OR=2.11,95%CI=1.30-3.41 and adjusted OR=1.88, 95%CI=1.15-3.05,respectively).PartⅡthe Relationship between the Polymorphism of Interleukin-1 Receptor Antagonist and Susceptibility to Cervical CancerInflammation is one of the most important tumor physiological response to infection.It will influence the clinical outcomes including many loci.There also may be a relationship between the genetic polymorphism of interleukin-1 receptor antagonist(IL-1RN)and susceptibility to cervical cancer,so we used PCR to explore such associations.The genotype frequencies of IL-1RN polymorphism were 89.2%for 1/1;9.1%for 1/2;1.2%for 2/2;0.2%for 1/3;0.2%for 1/4 and 0%for 4/4 in controls and 90.6%for 1/1;8.3%for 1/2;0%for 2/2;0.3%for 1/3; 0.5%for 1/4 and 0.3%for 4/4 in cases.No significant difference between the cases and controls was observed in any genotypes and their combinations.In a stratified analysis,no significant differences were observed in terms of the associations between IL-1RN genotypes and cervical cancer risk for individuals with age,mearche,pregnancies, residence and so on.PartⅢthe Relationship between the Plasma IL-1βLevels and Genotype-Phenotype Correlation and Susceptibility to Cervical CancerSome studies have showed that circulating IL-1βlevels were significantly different in patients with different grades of cervical lesions. The plasma IL-1βlevels in cervical cancer cases were significantly higher than those in health women,which was associated with the polymorphisms in IL-1 gene.However,the related study was absent in Chinese women.We conducted a hospital-based case-control study of 252 cervical cancer cases and 408 cancer-free controls in Jiangsu Province,to evaluate the associations of plasma IL-1βlevels and genotype-phenotype correlation and risk of cervical cancer.We found that the mean plama IL-1βlevel in cervical cancer cases was 53.96±32.21pg/ml,which was significantly higher than that in controls(40.61±20.43pg/ml,P＜0.001).High plasma IL-1βlevel (IL-1β＞38.00 pg/ml)was associated with a 2.45-fold increased risk of cervical cancer(adjusted OR=2.45,95%CI=1.70-3.55).Furthermore,in the joint effect analyses,subjects with high plasma IL-1βlevels,were associated with a 3.58-fold increased cervical cancer risk when simultaneously carrying -31TC/CC genotypes(adjusted OR=3.58;95% CI=1.95-6.58)and a 3.79-fold increased risk when carrying -511CT/TT genotypes(adjusted OR=3.79;95%CI=2.06-6.97),and the additive interaction was detected between plasma IL-1βlevel and IL-1B T-31C variant contributing to cervical cancer risk(P for interaction:0.004). However,there were no associations between IL-1 polymorphisms and plasma IL-1βlevels.