Alcohol consumption has been inconsistently associated with breast cancer risk. Recent studies suggest that genetic polymorphisms of glutathione S-transferases (GSTs) may modify this relation. To determine if breast cancer risk is associated with GSTM1 and GSTT1 genetic polymorphisms, and to evaluate the effect modification between GST genotypes and alcohol consumption in the risk of breast cancer, we conducted a case -control study in the state of Connecticut in the period 1998 and 2001. Cases were histologically confirmed, incident breast cancer patients in New Haven County, CT. Controls were randomly selected from women histologically confirmed to be without breast cancer. The study results show that, while GSTM1 genotypes were not associated with breast cancer risk, GSTT1-null genotype was associated with a significant 90% increased risk for postmenopausal women (OR ¼ 1.9, 95% CI 1.2 -3.0). Analysis by GST genotypes and alcohol consumption shows that GSTM1A ever-drinking women had a 2.5-fold (OR ¼ 2.5, 95% CI 1.1 -5.5) increased risk of breast cancer compared to the GSTM1A never-drinkers, and the risk increases with duration and daily amount of alcohol consumption. Postmenopausal women with GSTT1-null genotype, who consumed a lifetime of 4250 kg of spirit-equivalents, had an almost seven-fold increased risk (OR ¼ 6.8, 95% CI 1.4 -33.9), and drinking commencing at younger ages appears to carry a higher risk. An OR of 8.2 (95% CI 1.2 -57.4) was observed for those with GSTM1A, and GSTT1-null genotypes who had consumed a lifetime of 4250 kg of spirit-equivalents. In conclusion, alcohol consumption may increase breast cancer risk among those who carry susceptible GST genotypes.
Studies have suggested that breast cancer risk factor profiles may vary according to joint estrogen receptor (ER) and progesterone receptor (PR) tumor status. Most of the published literature to date which has investigated the association between exposure to organochlorine compounds and breast cancer has reported null or weak associations. If, indeed, the classification by hormonal receptor status identifies different forms of breast cancer, then assessing the risk of exposure to polychlorinated biphenyls (PCBs) on breast cancer as one disease or stratifying based on ER or PR status alone may obscure the association between PCBs and breast cancer. A hospital-based case-control study of 266 cases and 347 benign breast disease controls was conducted to examine the association of blood serum and adipose tissue concentrations of PCBs with breast cancer by joint ER/PR status. Total PCBs were measured in blood serum, and the following PCB congeners were measured in breast adipose tissue: 74, 118, 138, 153, 156, 170, 180, 183, 187. We did not detect any clear relationship or change in breast cancer risk based on joint ER/PR tumor status for body burden of PCBs, whether measured in blood serum or breast adipose tissue, by total PCBs or for specific congeners. These results confirm previous findings in the literature of no positive association between environmental exposure to PCBs and risk of breast cancer.
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