Haplotypes in the 5'-untranslated region of the CYP1A2 gene are inversely associated with lung cancer risk but do not correlate with caffeine metabolism.

In this study, we analyzed the influence of CYP1A2 genetic variation and enzyme activity on lung cancer risk in a high-incidence area. A total of 95 lung cancer patients and 196 controls were genotyped for the -3860G/A, -3113A/G, -2467T/delT, -739T/G, and -163C/A polymorphisms in the 5'-untranslated region of the gene. In addition, a subset of 70 patients and 115 controls were phenotyped by high-performance liquid chromatography determination of the caffeine metabolic ratio (CMR). The -2467T/delT polymorphism and the CYP1A2*1V haplotype (-163C>A, -2467T>delT) were inversely associated with lung cancer risk (odds ratio [OR] = 0.47 [0.2-0.9]; P = 0.02 and OR = 0.13 [0.02-1.0]; P = 0.04; respectively). In addition, the CYP*1A/*1V and *1F (-163C>A)/*1D (-163C>A, -2467T>delT) diplotypes were absent in the patients group, whereas accounting for 7.1% (P = 0.017) and 5.6% (P = 0.037) of controls, respectively. Mean CMR was significantly higher in patients than in controls (10.50 ± 17.31 vs. 6.52 ± 6.26, P = 0.01) but regression analyses did not yield significant ORs for the association with lung cancer risk. Similarly, no significant correlations were found between any genetic variant and enzyme activity. Several CYP1A2 haplotypes and diplotypes containing the -2467delT variant were associated with lower lung cancer risk; however, they did not correlate with significant changes in CYP1A2 metabolic activity toward caffeine.

Effectiveness of chitosan against mature biofilms formed by food related bacteria.

Chitosan has proven antimicrobial properties against planktonic cell growth. Little is known, however, about its effects on already established biofilms. Oriented for application in food industry disinfection, the effectiveness of both medium molecular weight (MMW) chitosan and its enzymatically hydrolyzed product was tested against mature biofilms of four pathogenic strains, Listeria monocytogenes, Bacillus cereus, Staphylococcus aureus and Salmonella enterica, and a food spoilage species, Pseudomonas fluorescens. Unexpectedly, log reductions were in some cases higher for biofilm than for planktonic cells. One hour exposure to MMW chitosan (1% w/v) caused a 6 log viable cell reduction on L. monocytogenes monospecies mature biofilms and reduced significantly (3-5 log reductions) the attached population of the other organisms tested, except S. aureus. Pronase-treated chitosan was more effective than MMW chitosan on all tested microorganisms, also with the exception of S. aureus, offering best results (8 log units) against the attached cells of B. cereus. These treatments open a new possibility to fight against mature biofilms in the food industry.

CYP1A1 gene polymorphisms increase lung cancer risk in a high-incidence region of Spain: a case control study.

BACKGROUND: A rural region in south-west Spain has one of the highest lung cancer incidence rates of the country, as revealed by a previous epidemiological 10-year follow-up study. The present work was undertaken to ascertain the role of CYP1A1 gene polymorphisms and their interaction with tobacco smoking in the development of the disease in this location. METHODS: One-hundred-and-three cases of lung cancer and 265 controls participated in the study. The participants were screened for the presence of four CYP1A1 polymorphisms, namely MspI, Ile462Val, T3205C, and Thr461Asn. Lung cancer risk was estimated as odds ratios (OR) and 95% confidence intervals (CI) using unconditional logistic regression models adjusting for age, sex, and smoking. RESULTS: The distribution of the variant CYP1A1 alleles was different from that described for other Caucasian populations, with CYP1A1*2A showing an uncommonly high frequency (p < 0.01). The CYP1A1*2B allele (carrying MspI and Ile462Val mutations) was strongly associated with high lung cancer risk (OR = 4.59, CI:1.4-12.6, p <0.01). The Ile462Val polymorphism was also shown to increase the risk for the disease (OR = 4.51, CI:1.8-11.9; p <0.01) and particularly for squamous-cell (OR = 5.01; CI: 1.6-14.3, p < 0.01) and small-cell lung carcinoma (SCLC) (OR = 6.97, CI: 1.2-81.3; p = 0.04). Moreover, the Thr461Asn polymorphism was found to be associated with SCLC in a Caucasian population for the first time to our knowledge (OR = 8.33, CI: 1.3-15.2, p = 0.04). CONCLUSION: The results suggest that CYP1A1 polymorphisms contribute to increase lung cancer susceptibility in an area with an uncommon high incidence rate.

GST polymorphisms interact with dietary factors to modulate lung cancer risk: study in a high-incidence area.

The aim of this study was to explore possible correlations between glutathione S-transferases (GST) polymorphisms, smoking, diet, and lung cancer susceptibility in a rural Spanish region with one of the highest incidence rates of the country. All lung cancer patients living in the area (103) and 247 matched controls were genotyped for the GST mu 1 (GSTM1) null, GST theta 1 (GSTT1) null, and GST pi 1 (GSTP1) Isoleucine (Ile) 105 valine (Val) polymorphisms and interviewed to gather information on smoking and dietary habits. Neither the presence of GST polymorphisms nor their interaction with smoking was independently associated to lung cancer risk. The intake of carotenoid-rich red and yellow vegetables was inversely associated with lung cancer (P < 0.05). Interestingly, this was observed only in carriers of the GSTM1 (P = 0.04), GSTT1 (P = 0.03), or GSTM1/T1 (P = 0.04) positive genotypes. Similarly, the consumption of citrus fruits was more frequent among cancer-free subjects who carried functional GSTM1 (P = 0.04) or both GSTM1 and GSTT1 enzymes (P = 0.04). The results show that the inverse association observed between the intake of dietary carotenoid-rich vegetables and lung cancer risk is dependent on the GST genotype. These results warrant further investigations to confirm the observed associations.

Adenosine triphosphate-binding cassette B1 (ABCB1) (multidrug resistance 1) G2677T/A gene polymorphism is associated with high risk of lung cancer.

BACKGROUND: P-glycoprotein (P-gp) is a transmembrane transporter that is encoded by the adenosine triphosphate-binding cassette B1 (ABCB1) (multidrug resistance 1) gene, which plays a role in cell defense against environmental attacks, like those generated by xenobiotics. P-gp is expressed in the lung, where it has been suggested to transport these compounds from the interstitium into the lumen. METHODS: Two functional ABCB1 polymorphisms were examined, G2677T/A (in exon 21) and C3435T (in exon 26), in a group of lung cancer patients and in a control group. RESULTS: Whereas 3435T allelic and genotype frequencies were unchanged between both study groups, lung cancer patients showed higher frequency of the 2677T variant allele compared with the control group (0.67 vs. 0.43; P < .001; odds ratio, [OR], 2.6; 95% confidence interval [95% CI], 1.7-4.0). Among the histologic tumor types that were included in the study, squamous cell carcinoma was associated most strongly with the presence of the 2677T allele (OR, 3.92; 95% CI, 2.2-6.9) and especially was associated with the 2677 TT genotype (OR, 6.75; 95% CI, 3.0-15.2). In a haplotype analysis, homozygous wild-type alleles were classified as genotype A, heterozygous alleles were classified as genotype B, and homozygous mutant allele were classified as genotype C both in exon 21 (first letter) and in exon 26 (second letter) loci. The haplotype CB displayed the highest association with lung cancer (OR, 18.09; 95% CI, 2.4-139.2). CONCLUSIONS: The current results taken together suggest that, aside from other known causes of lung cancer, such as tobacco smoke, the existence of polymorphisms in the ABCB1 gene and, specifically, the presence of the G2677T mutation can be crucial in conferring susceptibility to lung cancer. Further studies comprising larger populations are needed to confirm these preliminary findings.