rs1695
badMag 3.5This is a protein-altering variant in the GSTP1 gene.
Key Literature Trait Associations
Detoxification Capacity
The Ile105Val variant in glutathione S-transferase P1 alters the enzyme's substrate specificity and detoxification capacity. The G allele (Val105) reduces activity toward certain carcinogens but increases activity toward others. Relevant to chemotherapy drug metabolism and oxidative stress response.
Prostate cancer
The GG genotype of rs1695 is associated with an approximately 20% increased risk of prostate cancer compared to GA+AA genotypes (OR=1.20, 95%CI 1.05–1.38) in the largest meta-analysis to date covering 17,518 cases and 42,507 controls across 42 studies. An earlier meta-analysis of 51 urinary system cancer studies (11,762 cases, 15,150 controls) also confirmed significant association between the Val105 allele and urinary system malignancy, with prostate cancer driving the signal, particularly in Asian populations. The mechanistic basis is reduced GSTP1-mediated detoxification of prostate carcinogens including oxidative metabolites and environmental electrophiles.
Platinum-based chemotherapy response
The A allele (Ile105) of rs1695 is associated with differential response to platinum-based chemotherapy, particularly in non-small cell lung cancer (NSCLC). A meta-analysis of 111 studies and 18,196 subjects identified GSTP1 rs1695 as one of eleven key variants associated with overall response rate to platinum regimens, qualifying it as a candidate prognostic biomarker. The Ile105 (AA) genotype is thought to confer higher GSTP1 detoxification activity that more efficiently inactivates platinum compounds, potentially reducing drug efficacy, while Val105 carriers may retain more active platinum at tumor sites. An earlier single-center study (n=90) found Val105 carriers had a 5.75-fold lower odds of severe oxaliplatin-induced peripheral neuropathy.
Chronic obstructive pulmonary disease
The GG homozygous genotype of rs1695 is associated with elevated COPD susceptibility, particularly among Caucasians, based on a systematic review and meta-analysis of 59 studies. The homozygote and recessive genetic models both reached statistical significance in Caucasian subgroup analyses, consistent with the hypothesis that reduced GSTP1 Val105 detoxification of cigarette smoke oxidants and electrophiles promotes airway inflammation and emphysema. The variant's GWAS association with N-acetylphenylalanine (β=0.104, p=2×10⁻¹¹) additionally suggests altered amino acid metabolite handling that may contribute to oxidative lung pathology.
Lung cancer
The G allele (Val105) of rs1695 is associated with modestly elevated lung cancer risk, primarily in Asian populations and smokers. A large meta-analysis of 42 studies (12,304 cases, 15,729 controls) found no significant overall association but demonstrated significant risk in Asian and smoking subgroups. A China-focused meta-analysis of 13 studies (2,026 cases, 2,451 controls) found GG vs AA OR=1.36 (95%CI 1.01–1.84). The effect is thought to reflect reduced GSTP1-mediated detoxification of tobacco carcinogens including benzo[a]pyrene diol epoxide, with ethnicity-specific differences in background carcinogen exposure and linkage disequilibrium patterns.
Breast cancer
The G allele of rs1695 shows a significant association with breast cancer in Asian women but not in overall multi-ancestry analyses. The largest meta-analysis (36 studies, 20,615 cases and 20,481 controls) found no significant overall association, but in Asian women GG vs AA carried OR=1.40 (95%CI 1.06–1.88). A second meta-analysis of 41 studies (10,067 cases, 12,276 controls) found OR=1.16 (95%CI 1.01–1.34) in Caucasian women for GG vs AA. Mediterranean diet adherence may modify risk among Ile allele carriers. The ancestry-specific effects likely reflect differences in environmental carcinogen exposure and LD patterns across populations.
Asthma
The A allele (Ile105) of rs1695 shows a possible protective signal against asthma based on a meta-analysis of 17 GSTP1 Ile105Val studies, though extreme heterogeneity across studies limits interpretation. The Val105 allele (G) showed a weak possible protective effect against asthma phenotypes overall, with a negative association with bronchial hyper-responsiveness and a weak positive association with wheezing. The authors concluded that GST genes alone do not play a substantial role in asthma development, and no robust effect direction has been consistently replicated across independent cohorts.
▶GWAS Catalog Trait Associations (3)
Genome-wide significant associations (p < 5×10⁻⁸) from the NHGRI-EBI GWAS Catalog.
GWAS Catalog Trait Associations (3)
Genome-wide significant associations (p < 5×10⁻⁸) from the NHGRI-EBI GWAS Catalog.
▶ClinVar annotation
not provided; Abnormality of immune system physiology
View on ClinVar →▶Research that mentions this SNP (21)
▶Association of the matrix metalloproteinase 3 (MMP3) single nucleotide polymorphisms with tendinopathies: case-control study in high-level athletesCase reportNina Briški et al.(2021)· International Orthopaedics
This is a Turkish-language personalized nutrigenetics and epigenetics coaching report for individual Mehmet Efe Yildirim (Report No. 1332, dated 2023-11-21). The report analyzes the individual's genetic polymorphisms related to nutritional metabolism, food sensitivities, detoxification pathways, and other health-related traits, providing personalized dietary and lifestyle recommendations based on cited scientific literature. This is a direct-to-consumer genetic test report, not a peer-reviewed research study.
▶Evaluation of polymorphisms in repair and detoxification genes in alcohol drinkers and non‐drinkers using capillary electrophoresisAssociationN=82Caroline Oliveira de Araújo Melo et al.(2020)· ELECTROPHORESIS
Case-control study of 46 alcohol use disorder (AUD) patients and 36 controls from Brazil examining polymorphisms in GSTP1 (rs1695) and XRCC1 (rs7997782) genes involved in DNA repair and detoxification. The GG homozygote genotype in rs1695 (GSTP1) was significantly more frequent in AUD cases (40.6%) compared to controls (17.7%, p=0.023), with an odds ratio of 4.433 (95% CI 1.377-14.271). No polymorphism variation was observed in rs7997782 (XRCC1) as only wild-type homozygotes were present.
▶Glutathione‐S‐transferase P1 may predispose children to a decline in pulmonary function after stem cell transplantAssociationN=49Julie Stark et al.(2017)· Pediatric Pulmonology
A retrospective study of 49 pediatric stem cell transplant patients found that the GSTP1 SNP rs1695 was significantly associated with pulmonary function decline at 1 year post-SCT. Patients homozygous for the ancestral allele (A) showed greater decline in FEV1 (adjusted p<0.01) and FEF25-75 (adjusted p=0.02) compared to those with at least one minor allele (G), suggesting the Val158Met variant may provide protection against post-SCT pulmonary complications.
▶Association of 12 polymorphic variants conferring genetic risk to lung cancer in Indian population: An extensive meta‐analysisMeta-analysisN=19,556Debmalya Sengupta et al.(2017)· Environmental and Molecular Mutagenesis
A comprehensive meta-analysis of 50 case-control studies from the Indian subcontinent identified genetic variants modifying lung cancer risk, finding FDR-corrected associations for rs3547/XRCC1 (OR=1.83-2.72) and rs1048943/CYP1A1 (OR=2.07). The rs1048943/CYP1A1 variant showed strongest associations with adenocarcinoma (OR=3.38) and squamous cell carcinoma (OR=3.53) with significant effect modification by smoking status. Global meta-analysis confirmed rs1048943/CYP1A1 association across world populations (OR=1.22, p=0.01).
▶The relationship between polymorphisms of BDNFOS and BDNF genes and heroin addiction in the Han Chinese populationReviewTianbo Jin et al.(2016)· The Journal of Gene Medicine
This review examines neurogenetic and neuropharmacological correlates of opioid use disorder (OUD) with emphasis on ancestry-specific genetic risk profiles. The paper identifies multiple genes involved in the reward pathway (DRD2, DRD3, DRD4, OPRM1, OPRK1, OPRD1, BDNF, NRXN3, COMT, SLC6A4, KCNC1, KCNG2) and their variants associated with OUD susceptibility and treatment response across different ethnic populations, highlighting critical research disparities where African Americans and Hispanics have been underrepresented in genetic association studies.
▶Biological monitoring and the influence of genetic polymorphism of As3MT and GSTs on distribution of urinary arsenic species in occupational exposure workersAssociationN=201Beata Janasik et al.(2015)· International Archives of Occupational and Environmental Health
This study examined six genetic polymorphisms (As3MT Met287Thr rs11191439, As3MT 5'UTR rs7085104, As3MT rs3740393, As3MT rs3740400, GSTP1 rs1695, GSTO2 rs156697) in 149 copper mill workers and 52 controls. The As3MT rs3740400 GG homozygotes showed significantly higher percentage of inorganic arsenic (iAs) in urine (21.8±2.0% vs 16.0±2.1%, p<0.05) compared to GC+CC genotypes. GSTO2 rs156697 showed strong association with arsenic metabolite patterns. The study concluded that As3MT and GST genotypes may influence arsenic metabolism capacity.
▶Host genetic variations in glutathione-S-transferases, superoxide dismutases and catalase genes influence susceptibility to malaria infection in an Indian populationAssociationN=350Fernandes RC et al.(2015)· Molecular Genetics and Genomics
A case-control study of 200 malaria patients (100 P. vivax, 100 P. falciparum) and 150 healthy controls examined associations between polymorphisms in antioxidant enzyme genes and malaria susceptibility. GSTM1 deletion showed significant association with complicated P. vivax malaria (p=0.0007, OR=3.8, 95% CI 1.9-7.4). Polymorphisms in GSTP1 (rs1695), SOD1 (rs2234694), SOD2 (rs4880, rs1141718), SOD3 (rs2536512), and CAT (rs1001179) genes were also associated with malaria susceptibility, with SNP-SNP interactions identified through multifactor dimensionality reduction analysis.
▶Polymorphisms of NRF2 and NRF2 target genes in urinary bladder cancer patientsAssociationN=609Edyta Reszka et al.(2014)· Journal of Cancer Research and Clinical Oncology
A case-control study of 244 urinary bladder cancer patients and 365 controls examining polymorphisms in NRF2 and five antioxidant genes (GSTM1, GSTT1, GSTA1, GSTP1, SOD2). GSTM1 null genotype was significantly associated with increased BC risk (OR 1.85, 95% CI 1.30-2.62, p=0.001), while GSTT1 null showed protective effects. Significant gene-gene interactions were identified, particularly the GSTP1×GSTT1×SOD2 variant combination (OR 0.22, 95% CI 0.09-0.56, p=0.001).
▶A common and functional gene variant in the vascular endothelial growth factor a predicts clinical outcome in early‐stage breast cancerReviewGudrun Absenger et al.(2013)· Molecular Carcinogenesis
This document is a comprehensive collection of ~1,200 cancer-related research abstracts and summaries published in various journals (2013), covering clinical trials, pharmacogenomic studies, and mutation analyses across multiple cancer types including colorectal, breast, lung, lymphoma, and other malignancies. The collection documents associations between genetic variants (SNPs and somatic mutations), gene expression patterns, and cancer treatment outcomes, including studies on KRAS, EGFR, TP53, BRAF, and pharmacogenomic variants like CYP3A4 and UGT1A1.
▶Variation in PAH‐related DNA adduct levels among non‐smokers: The role of multiple genetic polymorphisms and nucleotide excision repair phenotypeAssociationN=111Arash Etemadi et al.(2013)· International Journal of Cancer
This study examined PAH-related DNA adduct levels in 111 female never-smokers from Iran, evaluating 21 SNPs in 14 xenobiotic metabolism genes and 12 SNPs in 8 DNA repair genes. DNA adduct levels were significantly lower with NAT2 slow alleles (β=-0.24, p=0.01) and ERCC5 non-risk genotype (β=0.16, p=0.04), but higher with MPO risk alleles (β=0.21, p=0.01). The combination of phase I genes and measured NER capacity explained 17% more variation in adduct levels than environmental exposure alone (r²=0.24 vs 0.07), demonstrating the importance of genetic polymorphisms in PAH metabolism and DNA repair capacity.
▶Associations of polymorphisms in the genes of FGFR2, FGF1, and RBFOX2 with breast cancer risk by estrogen/progesterone receptor statusAssociationN=2,416Yu‐Ling Cen et al.(2013)· Molecular Carcinogenesis
A hospital-based case-control study in rural and urban India (1,204 cases; 1,212 controls) examined genetic and lifestyle risk factors for breast cancer. Four SNPs in FGFR2 (rs1219648, rs2420946, rs2981575, rs2981582) showed positive associations with breast cancer (ORs 1.32-1.47). Additional SNPs in obesity and metabolic genes (rs374748 in FBN2, rs2922763 in HNF4G, rs2116830 in KCNMA1, rs11121832 in MTHFR, rs16886165 in MAP3K1, rs11594610 in TCF7L2, rs2274459 in MLN) were associated with increased breast cancer risk. Waist-to-hip ratio ≥0.95 showed strong association (OR 3.78; 95% CI 2.92-4.89), and women living first 20 years in rural areas showed protective effect (OR 0.77).
▶Sipa1 promoter polymorphism predicts risk and metastasis of lung cancer in ChineseReviewChenli Xie et al.(2013)· Molecular Carcinogenesis
This is a comprehensive journal compilation containing multiple oncology and pharmacogenomics studies published in 2013 across various journals. The collection includes 60+ papers covering cancer treatment outcomes, genetic polymorphisms predicting chemotherapy response and survival, pharmacogenetic variants in drug metabolism and DNA repair genes, and prognostic biomarkers in various cancer types including breast, lung, colorectal, hematologic malignancies, and others. Key findings include associations of XRCC1 variants (rs915927, rs76507, rs2854501, rs2854509, rs3213255) with bladder cancer chemotherapy survival, ABCG2 rs2725264 with lung cancer overall survival (HR 3.22), SLCO1B1 rs4149056 with methotrexate pharmacokinetics, MTHFR rs1801131 with acute lymphoblastic leukemia outcome, and ABCC3/GSTM variants with acute myeloid leukemia survival.
▶Glutathione S‐transferase P1 single nucleotide polymorphism predicts permanent ototoxicity in children with medulloblastomaCase reportN=106Surya Rednam et al.(2013)· Pediatric Blood & Cancer
A retrospective case series of 106 pediatric medulloblastoma patients showing that GSTP1 105 A>G polymorphism (rs1695) predicts permanent ototoxicity risk. Patients with AG/GG genotype had 4-fold increased risk of requiring hearing aids versus AA genotype (OR 4.0, 95%CI 1.2-13.6). The association was strongest when combined with high-dose craniospinal radiation, resulting in 8.4-fold ototoxicity risk (OR 8.4, 95%CI 1.4-49.9, p=0.005).
▶Possible contribution of GSTP1 and other xenobiotic metabolizing genes to vitiligo susceptibilityAssociationN=200Mikhail M. Minashkin et al.(2013)· Archives of Dermatological Research
A candidate gene association study in 100 Russian vitiligo patients and 100 controls identified a strong novel association between GSTP1 rs1138272 (Ala114Val, OR=13.03, Bonferroni-adjusted P=0.0015) and vitiligo susceptibility. Cumulative analysis of multiple xenobiotic metabolizing genes showed that carrying higher numbers of risk alleles was associated with increased vitiligo risk (9-16 vs 3-8 alleles: OR=2.79, P=0.00063), supporting a polygenic model for vitiligo involving detoxification pathway genes.
▶Polymorphic markers associated with severe oxaliplatin‐induced, chronic peripheral neuropathy in colon cancer patientsAssociationN=343Hong‐Hee Won et al.(2012)· Cancer
Genome-wide association study identifying genetic polymorphisms associated with severe oxaliplatin-induced chronic peripheral neuropathy (OXCPN) in colon cancer patients. Discovery analysis of 96 patients and validation in 247 patients identified 9 SNPs in 8 genes with nominal replication (P < 0.05), with the strongest association at rs10486003 in TAC1 (P = 4.84 × 10⁻⁷, OR = 0.32). A prediction model using 5 SNPs (rs10486003, rs2338, rs830884, rs843748, rs797519) achieved 72.8% accuracy in model development and 75.9% in model evaluation.
▶Genetic polymorphisms ofMPO,GSTT1,GSTM1,GSTP1,EPHX1andNQO1as risk factors of early‐onset lung cancerAssociationN=1,938Maria Timofeeva et al.(2010)· International Journal of Cancer
Case-control study (638 early-onset lung cancer cases, 1,300 controls) examining 17 SNPs and 2 deletion polymorphisms across MPO, GSTT1, GSTM1, GSTP1, EPHX1, and NQO1 genes. No significant overall associations with early-onset lung cancer risk; subgroup analyses revealed gender- and/or smoking-specific effects for EPHX1 (rs2854455, rs2234922), GSTP1 (rs1695, rs947895, rs4891), GSTT1, and NQO1 (rs1800566), but none survived Bonferroni correction.
▶MRP2 and GSTP1 polymorphisms and chemotherapy response in advanced non-small cell lung cancerAssociationN=113Ning Sun et al.(2010)· Cancer Chemotherapy and Pharmacology
A case-control study of 113 advanced non-small cell lung cancer (NSCLC) patients found that MRP2 C-24T (rs717620) and GSTP1 Ile105Val (rs1695) polymorphisms significantly predicted response to platinum-based chemotherapy. Patients carrying variant alleles (MRP2 C→T and GSTP1 A→G) showed improved treatment response, with adjusted ORs of 4.493 (P=0.002) and 2.881 (P=0.022) respectively. A DNA microarray-based genotyping method was used for SNP analysis.
▶Effect of interactions of glutathione S‐transferase T1, M1, and P1 and HMOX1 gene promoter polymorphisms with heavy smoking on the risk of rheumatoid arthritisAssociationN=3,976Brendan T. Keenan et al.(2010)· Arthritis & Rheumatism
Gene-environment interaction study in 549 Nurses' Health Study cases and controls replicated in 1,771 Swedish EIRA cases. Found significant additive (AP=0.53, p=0.0005) and multiplicative (p=0.05) gene-smoking interactions between GSTT1-null deletion and heavy smoking (>10 pack-years) on rheumatoid arthritis risk, with stronger effects for seropositive RA (AP=0.62, p<0.0001). Interaction replicated for ACPA-positive RA (AP=0.32, p=0.02). HMOX1 rs2071746 and GSTP1 rs1695 showed interactions with smoking in primary analysis but did not replicate. GSTM1-null showed no significant interactions.
▶Polymorphisms of drug‐metabolizing genes and risk of non‐Hodgkin lymphomaAssociationN=2,413Hee Nam Kim et al.(2009)· American Journal of Hematology
Population-based case-control study (713 NHL cases, 1,700 controls) in Korea examining associations between drug-metabolizing gene polymorphisms and non-Hodgkin lymphoma risk. GSTP1 rs1695 AG/GG genotypes were associated with decreased NHL risk (OR=0.66-0.67), while CYP1A1 rs1048943 AG/GG genotypes were associated with increased NHL risk (OR=1.26-1.32). Smoking did not modify these associations.
▶Genetic polymorphisms in glutathione S‐transferases and cytochrome P450s, tobacco smoking, and risk of non‐Hodgkin lymphomaAssociationN=1,115Briseis A. Kilfoy et al.(2009)· American Journal of Hematology
Population-based case-control study of 1,115 women examining GST and CYP polymorphisms in relation to non-Hodgkin lymphoma risk, with stratification by smoking status. Overall NHL risk was not significantly altered by variant polymorphisms, but increased risk of DLBCL in non-smokers was associated with GSTP1 variant G allele (OR=1.6, 95% CI: 1.0-2.3) and CYP1A1 variant G allele (OR=2.4; 95% CI: 1.0-5.7), while decreased risk was observed for CYP1B1 variant G allele (OR=0.6, 95% CI: 0.4-1.0).
▶Genetic Variation in Candidate Osteoporosis Genes, Bone Mineral Density, and Fracture Risk: The Study of Osteoporotic FracturesAssociationN=6,752Gregory J. Tranah et al.(2008)· Calcified Tissue International
A candidate gene association study of 6,752 women from the Study of Osteoporotic Fractures examined 31 polymorphisms in 18 candidate osteoporosis genes for associations with fracture risk and bone mineral density. ALOX15_G48924T (rs7220870) T/T genotype was associated with 33% higher hip fracture risk (HR=1.33, 95% CI 1.00-1.77); PRL_T228C (rs7739889) C alleles reduced nonvertebral fracture risk by ~20%; BMP2_A125611G (rs235764) G/G showed 51% higher vertebral fracture risk (OR=1.51, 95% CI 1.03-2.23); and MMP2_C595T (rs243865) T allele carriers had reduced vertebral fracture risk. No significant associations were found with total hip BMD.
Gene information from NCBI Gene. Variant classifications from ClinVar.
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