Polymorphisms and diazinon and malathion levels in the etiology of breastcancer: a case-controlstudy in Mazandaran Province, North of Iran

Abstract

Breast cancer is the first leading cause ofcancer-related death inwomen. Xenobiotic-Metabolizing Enzymes (XMEs) contributeto the detoxification of numerous cancer therapy-inducedproducts. In the metabolism of xenobiotics, cytochromeP450s or monooxygenases and Glutathione –s transferase(GSTs) perform an important function by catalyzingthe hydroxylation reaction andconjugationofglutathione(GSH) to a wide variety of xenobiotics. Pesticides, whichare excessively used in northern Iran, are one of the mostimportantrisk factors for breast cancer incidence. Theydetoxify by phase I and II enzymes. The aim of this studywas to evaluate the association of CYP1A1(rs4646421),CYP1B1(rs1056836),CYP2C8(rs1058930),CYP19A1(rs749292) and GSTP1(rs 1695) polymorphisms and serumlevels of pesticides (Diazinon and Malathion) with therisk of breast cancer in Mazandaran province. This crosssectionalcase-control study included 72 patients and 51healthy individuals who were recruited.It wasperformedbetweenOctober 2017 to May 2018 in Oncology departmentat Imam Hospital inSari City.Breast cancer patientswith knownclinicopathological characters and healthywomen, as control, were genotyped for genes polymorphismsby PCR-RFLP and GC-MS method used for quantificationof poisons.Chisquare test, Fisher exact test,andlogistic regression model were applied for statistical analysis.The results of the experiments showed that thereweresignificant relationships between two groups andthe age of the patients wassignificantly higher than thecontrol group(p = 0.044).Regarding the relationship betweenthe genotypes of each gene and breast cancer risk,using a logistic regression model in two normalized andage-adjusted models, it was determined that in CYP2C8genotype, those havingtheCGallele, increased the risk ofbreast cancer in adjusted model (CI=95%1.11,75.84).In the CYP19A1gene of individuals with GA genotype,the risk of breast cancer increasedinnon-adjusted model(CI95%=1/52-27/21) about the CYP1B1 gene, people withtwo genotypes of CG + GGwereassociated with a higherrisk of breast in non-adjusted and adjusted model (CI71/5– 19/1 95% =)( CI=95% 1.31,6.57). In CYP2C8gene,the Gallelehada protective effect on breast cancer and decreasedthe risk of breast cancer (P = 0.02) and in GSTP1gene,theGallele increased the riskof breast cancer(P=0.0480).Moreover,in CYP1B1 gene, G alleledecreased the riskofbreast cancer (P=0.0271).Regardingthe serum levels of OPs,Diazinon in the case group hada much lower level than thecontrol groupbut(p<0.001) there was a significant relationshipbetween serum levels of Diazinon and risk of breastcancer (p<0.001). The results of the current studyconfirmedthe association between CYP2C8(rs1058930),CYP19A1(rs749292) and CYP1B1(rs1056836)gene polymorphismsand increased the risk of breast cancer.Also,there was a significantrelationship between serum levels of Diazinon andrisk of breast cancerin women in Mazandaran province.