Interactions between genetic and environmental risk factors for cervical cancer

Cervical cancer (CC) is a dreaded disease among women causing approximately 500,000 deaths annually worldwide. Infection with high-risk human papillomavirus (HPV) plays a major role in the etiology of CC. However, most infected women do not develop cancer. Therefore, additional environmental and/or genetic cofactors might be involved. Ethnic differences might also account for the significantly higher incidence of CC among Hispanics, especially in Latin America, compared to U.S. Caucasians. I hypothesize that inheritance of certain polymorphic genes involved in the metabolism chemicals in cigarette smoke interacts with HPV to significantly increase the risk for CC. This molecular epidemiology study assessed the role of these risk factors for development of CC in women from the US and Venezuela. After being consented, women underwent a gynecologic examination with collection of exfoliated cells for a Papanicolaou smear and high-risk HPV DNA detection. Blood specimens were also collected to extract genomic DNA for genotyping by PCR methods. Controls were matched for age, ethnicity, and place of recruitment. A total of 300 subjects were recruited for this study, corresponding to 142 patients and 158 healthy controls. From this sample, 76 were selected as cases and 75 as controls in the U.S., and 38 as cases and 83 as controls in Venezuela. The mean age of the cases was 38.3 ± 12.7 years and of the controls was 36.2 ± 10.7 years. Cases were 44 times more likely to be infected with HPV than controls (p < 0.001). In addition, cancer patients from the U.S. were 4.9 times more likely to be infected with HPV than patients from Venezuela. Women who smoked >15 pack-years have a 2.9-fold increased risk for CC. Interactions between HPV and smoking were evidenced as smoker women with the variant genotype for epoxide hydrolase have a higher risk for CC (OR = 3.6). This study provided a better understanding of the differential contribution of risk factors for CC in the U.S. and Venezuela.