Association between UGT1A1*28*28 genotype and lung cancer in the Japanese population

Nishikawa, Yoshitaka; Kanai, Masashi; Narahara, Maiko; Tamon, Akiko; Brown, Jasmine; Taneishi, Kei; Nakatsui, Masahiko; Okamoto, Kazuya; Uneno, Yu; Yamaguchi, Daisuke; Tomono, Teruko; Mori, Yoshio; Matsumoto, Shigemi; Okuno, Yasushi; Muto, Manabu

doi:10.1007/s10147-016-1061-2

Cited by 5 publications

(3 citation statements)

References 20 publications

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“…This finding corroborates what was observed by Nishikawa et al ( 2016) [53] in their study of 194 patients with lung cancer, who found that the genotype homozygous TA7/7 increases the risk of developing lung cancer by approximately five times. They observed that squamous cell carcinoma was predominant in the lung cancer patients with genotype homozygous TA7/7 and smoking history, similar to our study.…”

Section: Discussionsupporting

confidence: 92%

UGT1A1 Gene Polymorphism Contributes as a Risk Factor for Lung Cancer: A Pilot Study with Patients from the Amazon

Pereira

Leitão

Andrade

et al. 2022

Genes

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Lung cancer is one of the most frequent neoplasms in the world. Because it is a complex disease, its formation occurs in several stages, stemming from interactions between environmental risk factors, such as smoking, and individual genetic susceptibility. Our objective was to investigate associations between a UGT1A1 gene polymorphism (rs8175347) and lung cancer risk in an Amazonian population. This is a pilot study, case-controlled study, which included 276 individuals with cancer and without cancer. The samples were analyzed for polymorphisms of the UGT1A1 gene (rs8175347) and genotyped in PCR, followed by fragment analysis in which we applied a previously developed set of informative ancestral markers. We used logistic regression to identify differences in allelic and genotypic frequencies between individuals. Individuals with the TA7 allele have an increased chance of developing lung adenocarcinoma (p = 0.035; OR: 2.57), as well as those with related genotypes of reduced or low enzymatic activity: TA6/7, TA5/7, and TA7/7 (p = 0.048; OR: 8.41). Individuals with homozygous TA7/7 have an increased chance of developing squamous cell carcinoma of the lung (p = 0.015; OR: 4.08). Polymorphism in the UGT1A1 gene (rs8175347) may contribute as a risk factor for adenocarcinoma and lung squamous cell carcinoma in the population of the Amazon region.

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Section: Discussionsupporting

confidence: 92%

UGT1A1 Gene Polymorphism Contributes as a Risk Factor for Lung Cancer: A Pilot Study with Patients from the Amazon

Pereira

Leitão

Andrade

et al. 2022

Genes

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“…The seven TA-repeats allele of UGT1A1*28 polymorphism underlying GS was investigated in relation to cancers of the endometrium [11], ovary [12], lung [13,14], breast [15], and prostate [16]. However, results of these studies were inconclusive, did not specifically investigate bilirubin as a putative cancer risk factor, and had limited sample size (range of number of cases 129 to 310), with the exception of Horsfall et al, where an inverse association was observed between genetically raised bilirubin levels and lung cancer risk among current smokers [14].…”

Section: Introductionmentioning

confidence: 99%

“…MR addresses unmeasured confounding (e.g., by smoking), which is a major limitation of observational studies [17]. The ten cancer types were investigated in large international consortia and selected based on previous evidence (cancers of the lung, ovary, endometrium, breast, and prostate) [11][12][13][14][15][16] or biological plausibility (pancreatic cancer, renal cell cancer, Hodgkin's lymphoma, melanoma, and neuroblastoma).…”

Section: Introductionmentioning

confidence: 99%

Genetically Raised Circulating Bilirubin Levels and Risk of Ten Cancers: A Mendelian Randomization Study

Khoei

Carreras‐Torres

Murphy

et al. 2021

Cells

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Bilirubin, an endogenous antioxidant, may play a protective role in cancer development. We applied two-sample Mendelian randomization to investigate whether genetically raised bilirubin levels are causally associated with the risk of ten cancers (pancreas, kidney, endometrium, ovary, breast, prostate, lung, Hodgkin’s lymphoma, melanoma, and neuroblastoma). The number of cases and their matched controls of European descent ranged from 122,977 and 105,974 for breast cancer to 1200 and 6417 for Hodgkin’s lymphoma, respectively. A total of 115 single-nucleotide polymorphisms (SNPs) associated (p < 5 × 10−8) with circulating total bilirubin, extracted from a genome-wide association study in the UK Biobank, were used as instrumental variables. One SNP (rs6431625) in the promoter region of the uridine-diphosphoglucuronate glucuronosyltransferase1A1 (UGT1A1) gene explained 16.9% and the remaining 114 SNPs (non-UGT1A1 SNPs) explained 3.1% of phenotypic variance in circulating bilirubin levels. A one-standarddeviation increment in circulating bilirubin (≈ 4.4 µmol/L), predicted by non-UGT1A1 SNPs, was inversely associated with risk of squamous cell lung cancer and Hodgkin’s lymphoma (odds ratio (OR) 0.85, 95% confidence interval (CI) 0.73–0.99, P 0.04 and OR 0.64, 95% CI 0.42–0.99, p 0.04, respectively), which was confirmed after removing potential pleiotropic SNPs. In contrast, a positive association was observed with the risk of breast cancer after removing potential pleiotropic SNPs (OR 1.12, 95% CI 1.04–1.20, p 0.002). There was little evidence for robust associations with the other seven cancers investigated. Genetically raised bilirubin levels were inversely associated with risk of squamous cell lung cancer as well as Hodgkin’s lymphoma and positively associated with risk of breast cancer. Further studies are required to investigate the utility of bilirubin as a low-cost clinical marker to improve risk prediction for certain cancers.

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Influence of UGT1A1 polymorphism on etoposide plus platinum-induced neutropenia in Japanese patients with small-cell lung cancer

et al. 2018

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Association between UGT1A12828 genotype and lung cancer in the Japanese population

Abstract: This is the first study to demonstrate a significant association between the homozygous UGT1A1*28 genotype and lung cancer.

Cited by 5 publications

References 20 publications

UGT1A1 Gene Polymorphism Contributes as a Risk Factor for Lung Cancer: A Pilot Study with Patients from the Amazon

UGT1A1 Gene Polymorphism Contributes as a Risk Factor for Lung Cancer: A Pilot Study with Patients from the Amazon

Genetically Raised Circulating Bilirubin Levels and Risk of Ten Cancers: A Mendelian Randomization Study

Influence of UGT1A1 polymorphism on etoposide plus platinum-induced neutropenia in Japanese patients with small-cell lung cancer

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