Abstract A49: GSTM1, GSTT1, GST polymorphisms, physical activity, and breast cancer risk in premenopausal women of European ancestry
Authors: Agurs-Collins Tanya , Iversen Edwin S. , Perna Frank , Baljinnyam Bolormaa 
Published: May 2019

Background: Susceptibility to premenopausal breast cancer may in part be attributable to inter-individual variability in GST genetic polymorphisms and lifestyle risk factors. Glutathione S-transferase (GST), a family of Phase II detoxification enzymes, may play an important role in breast cancer risk. GSTs are protective through their defense against free radicals and detoxification of toxic compounds, but may also participate in the activation of oxidative metabolites of carcinogenic compounds. Studies have postulated increased susceptibility to cancer in persons with GSTMI or GSTT1 deletions polymorphisms. In particular, inherited homozygous deletions of the GSTM1 and GSTT1 genotype can lead to the absence of enzyme activity, which is associated with increased breast cancer risk. Leisure time physical activity is associated with decreased breast cancer risk any may attenuate oxidative damage in subjects with GSTM1 and GSTT1 deletion genotypes. Hence, physical activity may protect against breast cancer through interaction with specific GST genotypes. We investigated associations between (1) GSTM1 and GSTT1 deletion genes, GST SNPs and premenopausal breast cancer risk; and (2) whether interactions between GST genotype and leisure time physical activity influenced breast cancer risk in women of European Ancestry.

Methods: The study design is a population-base case-control study (1476 cases and 699 controls) of premenopausal women (&lt;50 years of age). Study participants were first primary breast cancer cases and unaffected population-based controls recruited through three population-based registries from the Breast Cancer Family Registry. Clinical and epidemiologic data were taken from standardized family history and epidemiology questionnaires. The physical activity questionnaire provided data on the number of hours per week of leisure time exercise during specific age periods through-out life. Lifetime and recent (previous 3 years) physical activity was calculated using a previously described algorithm, which assigned 5.4 and 8.5 METs to moderate and strenuous activities, respectively, and corrected for demographic characteristics affecting MET value of activity. GSTM1 and GSTT1 deletion genes and 14 GST single nucleotide polymorphisms (SNP) were genotyped using TaqMan™real-time PCR technology. Logistic regression analysis was used to estimate odds ratios and corresponding 95% confidence intervals (CI) for associations between premenopausal breast cancer and GST deletion genotypes, GST SNPs and interactions by physical activity.

Results: We did not find robust statistically significant associations between the GST deletion genes, GST SNPS and physical activity with premenopausal breast cancer risk. After adjustment, GSTM3 SNP rs1332018 was nominally associated with the ER+/PR+ breast cancer subtype (p&lt;0.05). We found nominally significant interactions between two linked SNPs in the GSTM3 gene, rs7483 (a nonsynonymous SNP) and rs1537234, and level of recent physical activity for women with the ER-/PR- subtype (p&lt;0.01), after adjusting for known risk factors. However these associations were not significant after Bonferroni correction.

Conclusion: The observed associations between established GST deletion genotypes, GST SNPs and premenopausal breast cancer in women of European ancestry were not significant after accounting for multiple comparisons. However, results suggest that risk for ER-/PR- premenopausal breast cancer may change depending on level of physical activity in women with one or more GST risk alleles. Given the potential for public health impact, these results support a need for replication studies to confirm or refute these associations.

Citation Format: Tanya Agurs-Collins, Edwin S. Iversen, Frank Perna, Bolormaa Baljinnyam. GSTM1, GSTT1, GST polymorphisms, physical activity, and breast cancer risk in premenopausal women of European ancestry. [abstract]. In: Proceedings of the Twelfth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2013 Oct 27-30; National Harbor, MD. Philadelphia (PA): AACR; Can Prev Res 2013;6(11 Suppl): Abstract nr A49.