Journal of Experimental & Clinical Cancer Research 2009, 28:153 http://www.jeccr.com/content/28/1/153 Table 4: Haplotype frequencies in cases and controls stratified by cooking oil fume exposure status Haplotype All subjects Non exposure to cooking oil fume Exposure to cooking oil fume A-G-C A-G-T C-G-C P value Cases (%) Controls (%) 348 (61.1) 132 (23.1) 43 (7.5) 406 (71.2) 108 (18.9) 22 (3.9) OR [95%CI] 1.00 1.43 [1.07- 1.91] 2.28 [1.34- 3.89] < 0.001 Cases (%) Controls (%) 226 (62.6) 80 (22.0) 30 (8.2) 307 (73.1) 75 (17.8) 15 (3.6) OR [95%CI] 1.00 1.45 [1.01- 2.07] 2.72 [1.43- 5.17] < 0.001 Cases (%) Controls (%) 119 (57.4) 55 (26.2) 14 (6.9) 98 (65.5) 34 (22.3) 8 (5.2) OR [95%CI] 1.00 1.33 [0.81- 2.21] 1.44 [0.58- 3.58] 0.186 Abbreviation: OR, odds ratio; CI, confidence interval. According to our prior hypothesis and the SNP-based analyses, we considered the individuals with 751A-312G- 118C haplotype to be the reference group for OR estima- tions. The A-G-T and C-G-C haplotypes were associated with increased risk of lung adenocarcinoma (ORs were 1.43 and 2.28, 95%CIs were 1.07-1.91 and 1.34-3.89, respectively). Patients without exposure to cooking oil fume were more likely to have the A-G-T and C-G-C hap- lotypes than did controls with ORs of 1.45 (95%CI 1.01- 2.07) and 2.72 (95%CI 1.43-5.17), respectively. Among individuals with exposure to cooking oil fume, cases tended to be more likely to have the A-G-T and C-G-C haplotypes, however the findings were not statistically sig- nificant. Discussion In recent years, the etiological study of lung cancer remains popular all over the world. But the results are inconsistent, and as we know besides tobacco smoking, other impact factors of lung cancer are not definitive. Cig- arette smoking cannot fully explain the epidemiologic characteristics of lung cancer in Chinese women, who smoke rarely but have lung cancer relatively often. Undoubtedly non-smoking females are the ideal subjects to examine unknown, yet important environmental and genetic factors of lung cancer. And because adenocarci- noma represents the main subgroup of female lung cancer and is the most frequent subtype occurring in those who have never smoked, we studied the associations between risk for development of lung adenocarcinoma and multi- ple genetic polymorphisms in NER genes, as well as envi- ronmental factors among Chinese non-smoking female population. Our previous studies found the significant associations between cooking oil fume exposure and lung cancer risk in Chinese non-smoking females [5,8]. The similar results were suggested in the present study. Individuals with exposure to cooking oil fume had a 1.61-fold increased risk of developing lung adenocarcinoma (P = 0.009). It was reported that cooking oil fume condensates can induce DNA damage [9] and result in the increase of DNA cross-links in a certain concentration [10]. Some study showed that exposure to cooking oil fume could inhibit cell growth, increase TGFbeta1 secretion, and induce oxi- dative stress in lung epithelial cells [11]. There are other studies suggesting the important roles of cooking oil fume exposure in lung cancer risk among nonsmoking women [12-14]. Based on our results, 751C variant allele of ERCC2 gene may contribute to risk of lung adenocarcinoma, whereas the ERCC2 312 and ERCC1 118 polymorphisms have no significant associations with lung adenocarcinoma among non-smoking females. The three SNPs selected in this study are all in exons of NER genes, which were con- sidered to influence the protein activity, then decrease or increase the DNA repair capacity and finally associate with risk of cancer. The SNP at amino acid 751 of ERCC2 may be important in terms of ERCC2 protein activity [15], because it locate in the interactive domain, i.e. its helicase activator, p44, inside the TFIIH complex which is essential for transcription and NER [16]. The ERCC2 751 polymor- phism was associated with higher levels of chromatic aberrations [17] and DNA adducts levels in non-smokers [18]. It was reported that ERCC2 751AC/CC was signifi- cantly defective in NER [19] and had a modulating effect on DRC [20]. These results suggested that ERCC2 751 pol- ymorphism could result in a defect in NER and deficient DRC that may be responsible for increased susceptibility of cancer. Our results show that non-smoking females car- rying ERCC2 751C variant allele were at an increased risk for lung adenocarcinoma compared with those carrying AA genotype (adjusted OR = 1.64). It suggests that the pol- ymorphism of ERCC2 codon 751 plays an important role in the development of lung adenocarcinoma in non- smoking females. Previous studies in whole population got the same results [21,22]. However some reports found the non-correlation between the polymorphisms of ERCC2 gene and risk of lung cancer [23] or the opposite results [24]. The reason for these different conclusions is not clear now. Probably the size of the study population, Page 5 of 7 (page number not for citation purposes)