Nutrition, environment, and race are implicated in the etiology of several cancers. This study will assess the interrelationships of these three factors in cervical cancer, by examining the interaction of folate, smoking, and race. Smoking is an established risk factor for cervical cancer, but poor study designs, small sample sizes, and inadequate folate measurements have interfered with assessment of folate as a cervical cancer risk factor. Smoking has been associated with lower blood levels of folate, but we know of no study designed to test if the interaction between smoking and folate is associated with cancer. Many smoking-related cancers have disproportionately high mortality and incidence rates for black Americans. However, the interaction of nutrition with smoking has been relatively unexplored as a contributor to this racial disparity. By improving study design, increasing sample size, utilizing dietary folate equivalents (DFEs) and homocysteine levels (a functional marker of folate sufficiency) in assessing these inter-relationships, and sub-group analysis by race, our study will make a significant addition to the current body of knowledge. At three colposcopy clinics, 1500 women (50 percent black and 50 percent white race) will fill out a questionnaire on frequency of foods eaten, smoke exposure and other factors affecting folate levels and cervical cancer. Each woman will have blood drawn and cervical testing for 13 oncogenic human papillomavirus (HPV) types. Only women testing positive for these HPV types will be kept in the study. Women with cancer or cervical intraepithelial neoplasms 2 or 3 (CIN 2 or 3) on biopsies will be classified as """"""""high risk"""""""". All other oncogenic HPV positive women (with normal or CIN I biopsies) will be classified as """"""""low risk"""""""". Plasma will be tested for homocysteine. The interaction between folate (dietary intake or plasma homocysteine) and smoking associated with increased cervical cancer risk will be analyzed using ordinal logistic or logistic regression, including analysis by race. Cervical cancer has a step-wise histologic progression (which allows ordinal analysis or increase in the number of """"""""cases"""""""" collected in a short time period). It is one of the few cancers with a known necessary, though not sufficient, cause - HPV. By limiting analyses to women with HPV exposure, this study insures that all women have an equal chance of their smoking and folate exposure affecting whether they acquire the disease. This study may be the first cancer study to utilize DFEs, which reflect dietary folate bioavailability and are more likely to be associated with cancer risk than crude folate intake. Our study will be among the first to analyze the interaction of DFEs (or homocysteine) and cigarette associated with cancer. This study will have implications for smoking cessation, cancer prevention, folate supplementation and duration between Papanicolaou (Pap) smears. It may also explain some of the racial disparity in cervical cancer and possibly other smoking-related cancers.
