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

Abstract

Aim of the studyComplement 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 methodsThis 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.ResultsVariant 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).ConclusionsCFH 402H variant is a smoking-related risk factor for lung cancer, particularly the NSCLC.

Genetic polymorphisms of human cytochrome P450 CYP1A1 in an Egyptian population and tobacco-induced lung cancer

“…Our results showed an estimated risk for lung cancer 6.7 times greater in Egyptian smokers than in non-smokers compared to 2.61 times in a previous study [23] and an increased risk to develop lung cancer in males by 3.5-times than in females, which might be attributed to the higher incidence of smoking habit among males.…”

Prediction of Driver Modules via Balancing Exclusive Coverages of Mutations in Cancer Samples

“…For instance, CFH has been known to inhibit the complement pathway and to contribute to tumor growth. CFH was also reported to be associated with lung cancer . CR1 plays a crucial role in carcinogenesis and has been proved to be associated with an increased risk of developing non‐small cell lung cancer in Chinese population .…”

“…[46] CR1 plays a crucial role in carcinogenesis and has been proved to be associated with an increased risk of developing non-small cell lung cancer in Chinese population. Of the 12 genes (CFH, CHD8, CR1, EP400, F13A1, HCFC1, ITGAM, ITGAX, LILRB2, NAV1, and NAV2) that are not NCG cancer genes, several genes have been reported to be related to lung cancer.…”

Age to End Dreadful Diseases (HIV, Malaria, TB, Cancer and More): A Theory of Intact or Protected Complement (IPC) Immunity

“…Variant FH genotypes (Tyr/His and His/His) were over-presented among lung cancer patients compared to controls, a single nucleotide polymorphism (SNP) located in exon 9 of the FH gene [51]. It contains a tyrosine to histidine change at amino acid position 402 in the FH that re-directs the complement reactions.…”

“…It contains a tyrosine to histidine change at amino acid position 402 in the FH that re-directs the complement reactions. Tyr402His has been showed to be related with lung cancer and as a marker for lung adenocarcinoma [51]. The over-presentation of variant FH contributes to tumor growth by suppressing the anti-tumor cell and antibody mediated-responses was observed in the cell lines of several malignancies [51].…”