Association of CYP1A1 A4889G and T6235C polymorphisms with the risk of sporadic breast cancer in Brazilian women

Abstract

OBJECTIVES:We examined the influence of CYP1A1 A4889G and T6235C polymorphisms on the risk of sporadic breast cancer.METHOD:DNA from 742 sporadic breast cancer patients and 742 controls was analyzed using the polymerase chain reaction, followed by the restriction fragment length polymorphism technique.RESULTS:More patients had the CYP1A1 4889AG+GG genotype compared to controls (29.0% versus 23.2%, p=0.004). The G allele carriers had a 1.50-fold increased risk (95% CI: 1.14–1.97) of sporadic breast cancer compared to the other study participants. The frequency of the 4889AG+GG genotype among the Caucasian patients was higher than in the non-Caucasian patients (30.4% versus 20.2%, p=0.03) and controls (30.4% versus 23.2%, p=0.002). Caucasians and G allele carriers had a 1.61-fold increased risk (95% CI: 1.20–2.15) of sporadic breast cancer compared to other subjects. The CYP1A1 4889AG+GG genotype was more common among patients with a younger median age at first full-term pregnancy than among controls (33.8% versus 23.2%, p=0.001) and subjects whose first full-term pregnancies occurred at an older age (33.8% versus 26.1%, p=0.03). Women with the CYP1A1 4889AG+GG genotype and earlier first full-term pregnancies had a 1.87-fold (95% CI: 1.32–2.67) increased risk of sporadic breast cancer compared to the other study participants. Excess CYP1A1 4889AG+GG (39.8% versus 27.1%, p=0.01) and 6235TC+CC (48.4% versus 35.9%, p=0.02) genotypes were also observed in patients with grade I and II tumors compared to patients with grade III tumors and controls (39.8% versus 23.2%, p=0.04; 48.4% versus 38.6%, p=0.04). The G and C allele carriers had a 2.44-fold (95% CI: 1.48–4.02) and 1.67-fold (95% CI: 1.03–2.69) increased risk, respectively, of developing grade I and II tumors compared to other subjects.CONCLUSIONS:The CYP1A1 A4889G and T6235C polymorphisms may alter the risk of sporadic breast cancer in Brazilian women.

Association of Cytochrome CYP1A1 Gene Polymorphisms and Tobacco Smoking With the Risk of Breast Cancer in Women From Iraq

“…These distinguished observations became more obvious among smoking women with breast cancer. Others have reported that the increased risk of breast cancer was only among G mutant allele, but not C allele carriers ( 37 ), and influenced by smoking status ( 23 , 33 , 38 ). By contrast, others have failed to show such an association ( 15 ).…”

Роль Полиморфных Вариантов Генов Цитохрома P450 В Метаболизме Ксенобиотиков И Патогенезе Гемобластозов

“…В 2015 г. было проведено изучение влияния полиморфизмов A4889G и T6235C гена CYP1A1 на риск развития спорадического рака молочных желез, в результате было установлено, что у пациентов, страдающих злокачественными эпителиальными новообразованиями, достоверно чаще встречается генотип 4889AG + GG CYP1A1 [28].…”

Genetic Epidemiology of Breast Cancer in Latin America

“…Analyses of a limited number of candidate variants in hormone receptor genes (estrogen ( ESR1 ), androgen ( AR ), and progesterone receptors ( PGR )) yielded mostly negative results except in secondary stratified analyses (by body mass index or use of hormone replacement therapy) [ 148 , 149 , 150 , 151 , 152 ]. Studies conducted in Latin America focused on the ESR1 , PGR , COMT, CYP19A1 , and CYP1A1 genes [ 89 , 113 , 115 , 120 , 150 , 153 ]. One of these studies reported a positive association between an Alu insertion in the PGR gene and breast cancer risk [ 120 ], while other studies revealed statistically significant associations for polymorphisms within the CYP1A1 gene [ 113 , 115 ].…”