Journal of Experimental & Clinical Cancer Research 2009, 28:153 http://www.jeccr.com/content/28/1/153 Background In China, lung cancer is currently the most common can- cer among men and the second one among women and is the leading cause of cancer-related deaths for both gen- ders. The incidence and mortality rate of lung cancer in China urban populations have reached the number one among malignant tumors. Although the incidence and death rate of lung cancer is now declining in men, the inci- dence and death rate in women continues to increase. So in this sense it is more important to study the impact fac- tors of lung cancer in female population. Adenocarci- noma accounts for about 40% of all lung cancer, with a higher incidence in women. It is the most frequent sub- type occurring in those who have never smoked. The epi- demiologic characteristics and risk factors of lung cancer in nonsmokers are not clear. As we know, many lung can- cer patients didn't have the history of smoking and a lot of smokers didn't develop lung cancer [1], suggesting that host susceptibility factors may play an important role in this disease. Recent genetic susceptibility studies of cancer have focused on single nucleotide polymorphisms (SNPs) in candidate genes, among which DNA repair genes are increasingly studied because of their critical role in main- taining genome integrity. Excision repair cross-compli- mentary group 1 and group 2 (ERCC1 and ERCC2) are the important DNA repair genes, playing critical roles in nucleotide excision repair (NER) pathway which is the most important system to repair a wide variety of structur- ally DNA lesions, including bulky adducts, cross-links [2], oxidative DNA damage, thymidine dimmers [3]and alkylating damage [4]. The two genes are all located in chromosome 19q13.2-13.3. ERCC2 codes for an evolu- tionarily conserved helicase, a subunit of TFIIH complex which is essential for transcription and NER. ERCC1 pro- tein is responsible for recognition of DNA damage and removal of the damaged nucleotides in NER. SNPs in exons of DNA repair genes may influence their protein activity, resulting in differences of individual NER and DNA repair capacity (DRC) that may affect the suscepti- bility of lung cancer. So we selected the common SNPs in exons of ERCC2 and ERCC1 gene and with the frequency of heterozygosity >5% in the present study. The common polymorphism of ERCC1 gene is at codon 118 (C > T sub- stitution at exon 4, without amino acid change--Asn/Asn, rs11615). The common polymorphisms of ERCC2 gene is at codon 751 (A > C substitution at nucleotide position 35931, exon 23, Lys>Gln, rs13181) and codon 312 (G >A substitution at position 23951, exon 10, Asp>Asn, rs1799793). The polymorphisms at codon 312 and 751 have been studied extensively for their potential implica- tion in cancer risk. The effect of the ERCC2 and ERCC1 polymorphisms, and also of the haplotypes encompassing these two genes, on susceptibility of lung adenocarcinoma in non-smoking females has not been reported so far. In the present study, we describe a case-control study of lung adenocarcinoma in non-smoking female population in Shenyang, China, to evaluate the roles of the SNPs in ERCC1 and ERCC2 gene on risk of lung adenocarcinoma and explore the interaction between genetic polymorphism and exposure to environmental risk factors in the development of lung adenocarcinoma. Methods Study subjects and data collection In this hospital-based case-control study, the case group consisted of 285 diagnosed nonsmoking female patients (between January 2002 and November 2007) with histo- logically confirmed lung adenocarcinoma. At the same time controls were selected from cancer-free patients with other lung diseases but free of cancer history and symp- tom. Controls were all non-smoking females and fre- quency matched to cases on age (± 5 years). Controls suffered mainly from bronchitis, pneumonias, fibrosis, sarcoidosis, chronic obstructive pulmonary disease and emphysema. The human investigations were approved by the Institutional Review Board of China Medical Univer- sity, and informed consent was obtained from each partic- ipant or each participant's representatives if direct consent could not be obtained. All patients were all unrelated eth- nic Han Chinese. Each participant donated 10 ml venous blood and was interviewed to collect demographic data and environmen- tal exposures at the time they were admitted to the hospi- tal. Information concerning demographic characteristics, passive smoking, cooking oil fume exposure, fuel smoke exposure, family history of cancer, occupational exposure and dietary habit was obtained for each case and control by trained interviewers. Individual with a total of 100 cig- arettes in his lifetime was defined as a smoker, otherwise he was considered as a non-smoker. For cooking oil fume exposure, participants were asked about the frequency of cooking and types of oils. Subjects were also asked "How often did the air in your kitchen become filled with oily 'smoke' during cooking?" For each of these questions, there were four possible responses ranging from "never", "seldom", "sometimes", to "frequently". Exposure for cooking oil fume was categorized as an indicator variable equal to 1 if participants reported frequently or some- times, and equal to 0 otherwise. DNA isolation and genotyping Genomic DNA samples were isolated by guanidine hydro- chloride (GuHCl) method. SNPs were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method as described previ- ously [5]. The PCR primers (Takara Biotechnology Dalian Co. Ltd., China) for amplifying DNA fragment containing Page 2 of 7 (page number not for citation purposes)