Effect of Genetic Polymorphisms and Long-Term Tobacco Exposure on the Risk of Breast Cancer.

Zoraida Verde,Félix Gómez-Gallego,Alejandro Tejerina,Luis Reinoso-Barbero,Fernando Bandrés,Catalina Santiago,Luis Chicharro

doi:10.3390/ijms17101726

Zoraida Verde, Félix Gómez-Gallego + Show 5 more

Open Access

https://doi.org/10.3390/ijms17101726

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Abstract

Introduction: Tobacco smoke contains many potentially harmful compounds that may act differently and at different stages in breast cancer development. The focus of this work was to assess the possible role of cigarette smoking (status, dose, duration or age at initiation) and polymorphisms in genes coding for enzymes involved in tobacco carcinogen metabolism (CYP1A1, CYP2A6) or in DNA repair (XRCC1, APEX1, XRCC3 and XPD) in breast cancer development. Methods: We designed a case control study with 297 patients, 217 histologically verified breast cancers (141 smokers and 76 non-smokers) and 80 healthy smokers in a cohort of Spanish women. Results: We found an association between smoking status and early age at diagnosis of breast cancer. Among smokers, invasive carcinoma subtype incidence increased with intensity and duration of smoking (all Ptrend < 0.05). When smokers were stratified by smoking duration, we only observed differences in long-term smokers, and the CYP1A1 Ile462Ile genotype was associated with increased risk of breast cancer (OR = 7.12 (1.98–25.59)). Conclusions: Our results support the main effect of CYP1A1 in estrogenic metabolism rather than in tobacco carcinogen activation in breast cancer patients and also confirmed the hypothesis that CYP1A1 Ile462Val, in association with long periods of active smoking, could be a breast cancer risk factor.

Highlights

Tobacco smoke contains many potentially harmful compounds that may act differently and at different stages in breast cancer development
Genes such as NAT1, NAT2, CYP1A1, COMT, BRCA1, BRCA2 or DNA repair genes have been reported to alter the relationship between smoking and breast cancer risk [7,13,14,15]
We know that a weakness of our study is the low sample size, yet we believe this can be partly overcome by the fact that our population is homogeneous, not stratified and well defined in terms of phenotype assessment. These results suggest that cigarette smoking might play an important role in the development of breast cancer, when women start smoking relatively early in life or when they are exposed for a long time

Summary

Introduction

Tobacco smoke contains many potentially harmful compounds that may act differently and at different stages in breast cancer development. When smokers were stratified by smoking duration, we only observed differences in long-term smokers, and the CYP1A1 Ile462Ile genotype was associated with increased risk of breast cancer (OR = 7.12 (1.98–25.59)). Some studies have examined the risk of breast cancer according to genotypes that metabolize tobacco compounds in the human body or in genes related to DNA repair, with different results [3,12]. Genes such as NAT1, NAT2, CYP1A1, COMT, BRCA1, BRCA2 or DNA repair genes have been reported to alter the relationship between smoking and breast cancer risk [7,13,14,15]

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