Dataset Information

Complement factor H polymorphism rs1061170 and the effect of cigarette smoking on the risk of lung cancer.

ABSTRACT: AIM OF THE STUDY:Complement factor H (CFH) has been known to inhibit the complement pathway and to contribute to tumour growth by suppressing the anti-tumour cell mediated response in cell lines from several malignancies. We examined the association of Try402His single nucleotide polymorphism in CFH gene with lung cancer and the interaction with cigarette smoking. MATERIAL AND METHODS:This case-control study included 80 primary lung cancer patients and 106 control subjects who were genotyped for Try402His (rs1061170) by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. RESULTS:Variant genotypes (Tyr/His and His/His) were overpresented among patients compared to controls (p = 0.03, OR = 2.510, 95% CI: 1.068-5.899), and the frequency of variant H allele was significantly overexpressed in cases compared to controls (p = 0.021). Tyr/His genotype was identified in 100% of small cell lung cancer (SCLC) patients vs. 34.5% of non-SCLC (NSCLC), while 20.7% of NSCLC patients were homozygous for the variant allele (His/His) (p = 0.001). Binary logistic regression analysis revealed a 2.5 times greater estimated risk for NSCLC than for SCLC among variant allele carriers, and a 7.3-fold increased risk of lung cancer among variant allele smoking carriers vs. 1.3-fold increased risk among wild allele smoking carriers. Moreover, the stage of cancer positively correlated with smoking and pack-years in allele H carriers, and the correlation was stronger among those who were homozygous for it (His/His) than those who were heterozygous (Tyr/His). CONCLUSIONS:CFH 402H variant is a smoking-related risk factor for lung cancer, particularly the NSCLC.

SUBMITTER: Ezzeldin N

PROVIDER: S-EPMC4731447 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Complement factor H polymorphism rs1061170 and the effect of cigarette smoking on the risk of lung cancer.

Ezzeldin Nada N El-Lebedy Dalia D Darwish Amira A El-Bastawissy Ahmed A Shalaby Alaa Eldin AE

Contemporary oncology (Poznan, Poland) 20151208 6

<h4>Aim of the study</h4>Complement factor H (CFH) has been known to inhibit the complement pathway and to contribute to tumour growth by suppressing the anti-tumour cell mediated response in cell lines from several malignancies. We examined the association of Try402His single nucleotide polymorphism in CFH gene with lung cancer and the interaction with cigarette smoking.<h4>Material and methods</h4>This case-control study included 80 primary lung cancer patients and 106 control subjects who wer ...[more]

PMID: 26843839

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Project description:ImportanceThe risk of airflow limitation and chronic obstructive pulmonary disease (COPD) is influenced by combinations of cigarette smoking and genetic susceptibility, yet it remains unclear whether gene-by-smoking interactions are associated with quantitative measures of lung function.ObjectiveTo assess the interaction of cigarette smoking and polygenic risk score in association with reduced lung function.Design, setting, and participantsThis UK Biobank cohort study included UK citizens of European ancestry aged 40 to 69 years with genetic and spirometry data passing quality control metrics. Data was analyzed from July 2020 to March 2021.ExposuresPRS of combined forced expiratory volume in 1 second (FEV1) and percent of forced vital capacity exhaled in the first second (FEV1/FVC), self-reported pack-years of smoking, ever- vs never-smoking status, and current- vs former- or never-smoking status.Main outcomes and measuresFEV1/FVC was the primary outcome. Models were used to test for interactions with models, including the main effects of PRS, different smoking variables, and their cross-product terms. The association between pack-years of smoking and FEV1/FVC were compared for those in the highest vs lowest decile of estimated genetic risk for low lung function.ResultsWe included 319 730 individuals, of whom 24 915 (8%) had moderate-to-severe COPD cases, and 44.4% were men. Participants had a mean (SD) age 56.5 of (8.02) years. The PRS and pack-years were significantly associated with lower FEV1/FVC (PRS: β, -0.03; 95% CI, -0.031 to -0.03; pack-years: β, -0.0064; 95% CI, -0.0064 to -0.0063) and the interaction term (β, -0.0028; 95% CI, -0.0029 to -0.0026). A stepwise increment in estimated effect sizes for these interaction terms was observed per 10 pack-years of smoking exposure. The interaction of PRS with 11 to 20, 31 to 40, and more than 50 pack-years categories were β (interaction) -0.0038 (95% CI, -0.0046 to -0.0031); -0.013 (95% CI, -0.014 to -0.012); and -0.017 (95% CI, -0.019 to -0.016), respectively. There was evidence of significant interaction between PRS with ever- or never- smoking status (β, interaction; -0.0064; 95% CI, -0.0068 to -0.0060) and current or not-current smoking (β, interaction; -0.0091; 95% CI, -0.0097 to -0.0084). For any given level of pack-years of smoking exposure, FEV1/FVC was significantly lower for individuals in the tenth decile (ie, highest risk) than the first decile (ie, lowest risk) of genetic risk. For every 20 pack-years of smoking, those in the tenth decile compared with the first decile of genetic risk showed nearly a 2-fold reduction in FEV1/FVC.Conclusions and relevanceCOPD is characterized by diminished lung function, and our analyses suggest there is substantial interaction between genome-wide PRS and smoking exposures. While smoking was associated with decreased lung function across all genetic risk categories, the associations were strongest in individuals with higher estimated genetic risk.

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Complement factor H polymorphism rs1061170 and the effect of cigarette smoking on the risk of lung cancer.

Publications

Complement factor H polymorphism rs1061170 and the effect of cigarette smoking on the risk of lung cancer.

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