Meta-analysis of genetic polymorphisms in xenobiotic metabolizing enzymes and their association with breast cancer risk

Hussain, Tajamul; Alrokayan, Salman A.; Upadhyay, Upasna; Pavithrakumari, Manickam; Jayapriya, Jaganathan; Kutala, Vijay Kumar; Naushad, Shaik Mohammad

doi:10.1007/s12041-018-0946-4

Cited by 16 publications

(8 citation statements)

References 112 publications

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“…GSTs are phase II enzymes involved in detoxifying xenobiotics and oxidative stress by‐products through catalysis of glutathione conjugation . GSTM1 and GSTT1 null genotypes (i.e., homozygous deletions resulting in loss of enzyme activity) have both been associated with increased serum iron and oxidative stress biomarkers and elevated breast cancer risk . In our study, GSTT1 deletion polymorphism (alone or in combination with GSTM1 ) was not only independently associated with breast cancer risk (Supporting Information Table S6) but also modified associations between total/dietary (and nonheme) iron and breast cancer risk.…”

Section: Discussionsupporting

confidence: 46%

“…41 GSTM1 and GSTT1 null genotypes (i.e., homozygous deletions resulting in loss of enzyme activity) have both been associated with increased serum iron and oxidative stress biomarkers 42,43 and elevated breast cancer risk. 44 In our study, GSTT1 deletion polymorphism (alone or in combination with GSTM1) was not only independently associated with breast cancer risk (Supporting Information - Table S6) but also modified associations between total/dietary (and nonheme) iron and breast cancer risk. Several studies assessing other prooxidant exposures (e.g., smoking, alcohol) also reported stronger positive associations in women with null GSTT1 and/or GSTM1 genotypes.…”

Section: Discussionmentioning

confidence: 50%

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Iron intake, oxidative stress‐related genes and breast cancer risk

Chang

Cotterchio

Bondy

et al. 2020

Intl Journal of Cancer

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Iron has been suggested to contribute to breast cancer development through oxidative stress generation. Our study investigated associations between iron intake and breast cancer risk, overall and by menopausal and estrogen receptor/ progesterone receptor (ER/PR) status, and modification by oxidative stress-related genetic polymorphisms (MnSOD, GSTM1 and GSTT1). A population-based case-control study (3,030 cases and 3,402 controls) was conducted in Ontario, Canada. Iron intake (total, dietary, supplemental, heme, nonheme) was assessed using a validated food frequency questionnaire. Odds ratios (OR) and 95% confidence intervals (CI) were estimated from multivariable logistic regression models. Interactions between iron intake and genotypes were assessed among 1,696 cases and 1,761 controls providing DNA. Overall, no associations were observed between iron intake and breast cancer risk. Among premenopausal women, total, dietary and dietary nonheme iron were positively associated with ER-/PR-breast cancer risk (all p trend < 0.05). Among postmenopausal women, supplemental iron was associated with reduced breast cancer risk (OR >18 vs. 0 mg/day = 0.68, 95% CI: 0.51-0.91), and dietary heme iron was associated with an increased risk, particularly the ER-/PR-subtype (OR highest vs. lowest quintile = 1.69, 95% CI: 1.16-2.47; p trend = 0.02). Furthermore, GSTT1 and combined GSTM1/GSTT1 polymorphisms modified some of the associations. For example, higher dietary iron was most strongly associated with increased breast cancer risk among women with GSTT1 deletion or GSTM1/GSTT1 double deletions (p interaction < 0.05). Findings suggest that iron intake may have different effects on breast cancer risk according to menopausal and hormone receptor status, as well as genotypes affecting antioxidant capacity.

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Section: Discussionsupporting

confidence: 46%

Section: Discussionmentioning

confidence: 50%

Iron intake, oxidative stress‐related genes and breast cancer risk

Chang

Cotterchio

Bondy

et al. 2020

Intl Journal of Cancer

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“… 48 Two seminal meta-analysis reviews that examined the association between CYP1A (rs1048943) and breast cancer found conflicting results. 23 , 49 One Japanese study revealed that AG genotype was associated with reduced risks (protective effect). 23 While there was a consistent positive association between the variant and increased occurrence of breast cancer in Indian population, 50 there was no association in the African-American and white women.…”

Section: Discussionmentioning

confidence: 99%

Genetic Variations in Cytochrome P450 1A1 and 1B1 Genes in a Cohort of Patients from Iraq Diagnosed with Breast Cancer

Ibrahem

Ahmed

Amin

2021

Breast Cancer�(Auckl)

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Breast cancer is the most prevalent malignant neoplasm in females. Genetic variations in the xenobiotic metabolising cytochrome enzymes; Family 1 Subfamily A Member 1 (CYP1A1) and Family 1 Subfamily B Member 1 (CYP1B1) might play a role in the individual susceptibility to breast cancer and its prognosis. The goal of this study is to estimate the incidence of single nucleotide polymorphisms (SNPs) in CYP1A1 (rs1048943, Ile462VaI, and rs4646903/MSP1) and in CYP1B1 (rs1056836, Leu432Val) genes in patients with breast cancer. This case-control study included 180 female patients with breast cancer and 180 healthy control subjects from Kirkuk/Iraq. Genomic DNA was extracted from venous blood samples and tested for SNPs by the direct DNA sequencing technique. A statistical analysis was done to identify if there is any association between SNPs and the increasing odd of breast cancer and its stage, grade and molecular subtype at diagnosis. The common (reference) genotype of CYP1A1 gene rs1048943 is AA. The AG and GG variant genotypes were significantly more common in the breast cancer patients and conferred an increased odd of breast cancer and its later stages (stages III and IV) and poor differentiation ( P < .01) but not with the molecular subtypes. The common genotype of CYP1A1 rs4646903 is TT. The variant genotypes TC and CC are not associated either with increased risk of breast cancer ( P > .05) or with its stage, grade or molecular subtypes ( P > .05). The GG genotype of CYP1B1 rs1056836 was the common genotype. The CG and CC variant genotypes were not associated with the increased risks of breast cancer ( P > .05) or its stage, grade or molecular subtypes ( P > .05). In conclusion, variants genotypes of CYP1A1 rs1048943 might play a role in breast cancer pathogenesis and prognosis and can have a place in cancer screening and tailored medicine in the future in the Iraqi population. Future larger scale studies including other genes might help to better understand the role of the SNP in breast risk and its prognosis.

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“…Given the activity of GST enzyme towards carcinogen detoxification, the deficiency of GST-μ and GST-θ enzyme activity caused by deletions in GSTM1 and GSTT1 genes may compromise an individual's ability to deactivate carcinogens, leading to be involved in carcinogenesis (17) . A 2018 meta-analysis of fifty-three studies for GSTM1 polymorphism and forty-four studies for GSTT1 polymorphism found that GSTM1 and GSTT1 null genotypes were risk factors for breast cancer (OR were 1•22 and 1•07, respectively) (18) . However, our data demonstrated that GSTM1 and GSTT1 polymorphisms were not significantly associated with the risk of breast cancer.…”

Section: Discussionmentioning

confidence: 99%

“…GSTT1 and GSTM1 polymorphisms are caused by a deletion of the genes, which leads to a complete lack of the encoding protein (17) . Previous studies suggested that the mutant of GSTP1 and the deficiency in GSTT1 and GSTM1 may be related with the susceptibility to breast cancer, but the results remained inconsistent due to the sparse data of some studies or without considering adjustment for various potential confounders in multivariable models (18)(19)(20) .…”

mentioning

confidence: 99%

Intake of total cruciferous vegetable and its contents of glucosinolates and isothiocyanates, glutathione S-transferases polymorphisms and breast cancer risk: a case–control study in China

Zhang

Lin

et al. 2020

Br J Nutr

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Cruciferous vegetables contain high levels of glucosinolates (GSL) and isothiocyanates (ITC). ITC are known to induce glutathione S-transferases (GST) and thus exert their anticarcinogenic effects. This study explored the combined effects of cruciferous vegetable, GSL and ITC intake and GST polymorphisms on breast cancer risk. A total of 737 breast cancer cases and 756 controls were recruited into this case–control study. OR and 95 % CI were assessed by multivariable logistic regression. Higher cruciferous vegetable, GSL and ITC intakes were inversely associated with breast cancer risk, with adjusted OR of 0·48 (95 % CI 0·35, 0·65), 0·54 (95 % CI 0·40, 0·74) and 0·62 (95 % CI 0·45, 0·84), respectively. Compared with women carrying the GSTP1 rs1695 wild AA genotype and high cruciferous vegetable, GSL or ITC intake, carriers of the AA genotype with low cruciferous vegetable, GSL and ITC intake had greater risk of breast cancer, with adjusted OR of 1·43 (95 % CI 1·01, 1·87), 1·34 (95 % CI 1·02, 1·75) and 1·37 (95 % CI 1·05, 1·80), respectively. Persons with the GSTM1-null genotype and lower intake of cruciferous vegetables, GSL and ITC had higher risk of breast cancer than those with the GSTM1-present genotype and higher intake, with OR of 1·42 (95 % CI 1·04, 1·95), 1·43 (95 % CI 1·05, 1·96) and 1·45 (95 % CI 1·06, 1·98), respectively. Among women possessing the GSTT1-present genotype, low intake of cruciferous vegetables, GSL or ITC was associated with higher risk of breast cancer. But these interactions were non-significant. This study indicated that there were no significant interactions between cruciferous vegetable, GSL or ITC intake and GST polymorphisms on breast cancer risk.

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Meta-analysis of genetic polymorphisms in xenobiotic metabolizing enzymes and their association with breast cancer risk

Cited by 16 publications

References 112 publications

Iron intake, oxidative stress‐related genes and breast cancer risk

Iron intake, oxidative stress‐related genes and breast cancer risk

Genetic Variations in Cytochrome P450 1A1 and 1B1 Genes in a Cohort of Patients from Iraq Diagnosed with Breast Cancer

Intake of total cruciferous vegetable and its contents of glucosinolates and isothiocyanates, glutathione S-transferases polymorphisms and breast cancer risk: a case–control study in China

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