Polymorphisms in XPC, XPD, XRCC1, and XRCC3 DNA repair genes and lung cancer risk in a population of Northern Spain

<p>Abstract</p> <p>Background</p> <p>Polymorphisms in DNA repair genes have been associated to repair DNA lesions, and might contribute to the individual susceptibility to develop different types of cancer. Nucleotide excision repair (NER), base excision repair (BER), and double-strand break repair (DSBR) are the main DNA repair pathways. We investigated the relationship between polymorphisms in two NER genes, <it>XPC </it>(poly (AT) insertion/deletion: PAT-/+) and <it>XPD </it>(Asp312Asn and Lys751Gln), the BER gene <it>XRCC1 </it>(Arg399Gln), and the DSBR gene <it>XRCC3 </it>(Thr241Met) and the risk of developing lung cancer.</p> <p>Methods</p> <p>A hospital-based case-control study was designed with 516 lung cancer patients and 533 control subjects, matched on ethnicity, age, and gender. Genotypes were determined by PCR-RFLP and the results were analysed using multivariate unconditional logistic regression, adjusting for age, gender and pack-years.</p> <p>Results</p> <p>Borderline association was found for <it>XPC </it>and <it>XPD </it>NER genes polymorphisms, while no association was observed for polymorphisms in BER and DSBR genes. <it>XPC PAT+/+ </it>genotype was associated with no statistically significant increased risk among ever smokers (OR = 1.40; 95%CI = 0.94–2.08), squamous cell carcinoma (OR = 1.44; 95%CI = 0.85–2.44), and adenocarcinoma (OR = 1.72; 95%CI = 0.97–3.04). <it>XPD </it>variant genotypes (<it>312Asn/Asn </it>and <it>751Gln/Gln</it>) presented a not statistically significant risk of developing lung cancer (OR = 1.52; 95%CI = 0.91–2.51; OR = 1.38; 95%CI = 0.85–2.25, respectively), especially among ever smokers (OR = 1.58; 95%CI = 0.96–2.60), heavy smokers (OR = 2.07; 95%CI = 0.74–5.75), and adenocarcinoma (OR = 1.88; 95%CI = 0.97–3.63). On the other hand, individuals homozygous for the XRCC1 <it>399Gln </it>allele presented no risk of developing lung cancer (OR = 0.87; 95%CI = 0.57–1.31) except for individuals carriers of <it>399Gln/Gln </it>genotype and without family history of cancer (OR = 0.57; 95%CI = 0.33–0.98) and no association was found between <it>XRCC3 </it>Thr241Met polymorphism and lung cancer risk (OR = 0.92; 95%CI = 0.56–1.50), except for the <it>241Met/Met </it>genotype and squamous cell carcinoma risk (OR = 0.47; 95%CI = 0.23–1.00).</p> <p>Conclusion</p> <p>In conclusion, we analysed the association between <it>XPC</it>, <it>XPD</it>, <it>XRCC1</it>, and <it>XRCC3 </it>polymorphisms and the individual susceptibility to develop lung cancer in the Spanish population, specifically with a highly tobacco exposed population. We attempt to contribute to the discovery of which biomarkers of DNA repair capacity are useful for screening this high-risk population for primary preventing and early detection of lung cancer.</p

Polymorphism +17 C/G in Matrix Metalloprotease MMP8 decreases lung cancer risk

<p>Abstract</p> <p>Background</p> <p>Matrix metalloproteases (MMPs) constitute a family of enzymes capable of degrading different components of the extracellular matrix and are implicated in the invasion of tumor cells through the basement membrane. Polymorphisms in MMP genes may result in changes in the expression of MMPs being associated with the development and progression of cancer. We have investigated the association between three polymorphisms (-1607 1G/2G, +17 C/G and -77 A/G) in the human collagenases MMP1, MMP8 and MMP13 and the risk of development or progression of lung cancer.</p> <p>Methods</p> <p>A hospital-based case-control study was designed including 501 lung cancer patients and 510 controls matched. Genotypes were determined by PCR-RFLP. Results were analyzed using unconditional logistic regression, Cox's proportional hazard regression, and the Kaplan-Meier method.</p> <p>Results</p> <p>The MMP1 and MMP13 promoter polymorphisms were not associated with lung cancer risk, while the C/G polymorphism in MMP8 was associated with a statistically significant decreased risk of developing lung cancer (ORadj = 0.65; 95%CI = 0.45–0.93). The Kaplan-Meier analysis showed that the polymorphisms in MMP1, MMP8 and MMP13 not seem to modify the overall survival. Multivariate analysis revealed that MMP1, MMP8 and MMP13 polymorphisms are not independent prognostic factors for overall survival.</p> <p>Conclusion</p> <p>This study suggests that the polymorphism in MMP8 is associated with a decreased lung cancer risk, which can be used as a prognostic marker in lung cancer.</p

Genetic polymorphisms in <it>CYP1A1</it>, <it>GSTM1</it>, <it>GSTP1</it> and <it>GSTT1</it> metabolic genes and risk of lung cancer in Asturias

<p>Abstract</p> <p>Background</p> <p>Metabolic genes have been associated with the function of metabolizing and detoxifying environmental carcinogens. Polymorphisms present in these genes could lead to changes in their metabolizing and detoxifying ability and thus may contribute to individual susceptibility to different types of cancer. We investigated if the individual and/or combined modifying effects of the <it>CYP1A1 MspI</it> T6235C, <it>GSTM1 present/null</it>, <it>GSTT1 present/null</it> and <it>GSTP1 Ile105Val</it> polymorphisms are related to the risk of developing lung cancer in relation to tobacco consumption and occupation in Asturias, Northern Spain.</p> <p>Methods</p> <p>A hospital-based case–control study (CAPUA Study) was designed including 789 lung cancer patients and 789 control subjects matched in ethnicity, age, sex, and hospital. Genotypes were determined by PCR or PCR-RFLP. Individual and combination effects were analysed using an unconditional logistic regression adjusting for age, pack-years, family history of any cancer and occupation.</p> <p>Results</p> <p>No statistically significant main effects were observed for the carcinogen metabolism genes in relation to lung cancer risk. In addition, the analysis did not reveal any significant gene-gene, gene-tobacco smoking or gene-occupational exposure interactions relative to lung cancer susceptibility. Lastly, no significant gene-gene combination effects were observed.</p> <p>Conclusions</p> <p>These results suggest that genetic polymorphisms in the <it>CYP1A1</it>, <it>GSTM1</it>, <it>GSTT1</it> and <it>GSTP1</it> metabolic genes were not significantly associated with lung cancer risk in the current study. The results of the analysis of gene-gene interactions of <it>CYP1A1 Msp</it>I T6235C, <it>GSTM1</it> present/null, <it>GSTT1</it> present/null and <it>GSTP1</it> Ile105Val polymorphisms in lung cancer risk indicate that these genes do not interact in lung cancer development.</p