PHG Foundation | Genetic and environmental factors linked with breast cancer

Genetic and environmental factors linked with breast cancer
4 June 2010 | By Dr Susmita Chowdhury | Research article

Most complex diseases including breast cancer are associated with both genetic and environmental risk factors. It is well established that several environmental and lifestyle factors such as childbearing, hormone replacement therapy (HRT), obesity, alcohol consumption are significantly associated with breast cancer. To date, 17 genetic variants or SNPs (single nucleotide polymorphisms) have been identified, which account for around 8% of breast cancer risk. However, there have been inconsistent findings related to the possible interactions between the effects of variants and environmental risk factors. Gene–environment interactions mean that some people carry genetic factors that confer susceptibility or resistance to a certain disorder only in particular environments.

In order to test for evidence of gene-environment interactions in relation to breast cancer, researchers compared the genotypic relative risks for 12 SNPs across categories for ten established environmental risk factors in one of the largest prospective UK cohorts [Travis et al. 2 June 2010 doi:10.1016/S0140-6736(10)60636-8]. 7160 cases with breast cancer and 10196 controls from the Million Women Study cohort were included in the final analyses. Information for both cases and controls about the ten environmental risk factors (age at menarche, parity, age at first child birth, breastfeeding, menopausal status, age at menopause, use of HRT, body mass index, height and alcohol consumption) was recorded at the time the women joined the study. For this study cases and controls were mixed and genotyped by laboratory personnel unaware of the sample status.

120 separate statistical tests for gene-environment interaction were carried out and no significant association was found between 11 of the 12 polymorphisms and the ten risk factors. For the 12th SNP, there was a significant association with height, with taller women at slightly increased risk of breast cancer. The results of this study suggest that the low-penetrance susceptibility loci investigated here do not generally affect breast cancer risk through mechanisms involving these environmental factors. The only major environmental risk factor not studied here is postmenopausal hormone concentrations in the blood.

Comment: Though this is one of the largest studies to investigate gene-environment interaction in relation to breast cancer, tens of thousands of cases will be needed to assess reliably a comprehensive range of biologically plausible gene-environment interactions. The design of this study is generally sound, with a few limitations such as lack of information about risk in young women, multiple testing and relatively few a-priori hypotheses. The findings of the study are generally reassuring because, as genetic and environmental factors independently increase breast cancer risk, women with inherited genetic variants can still reduce breast cancer risk by modifying their lifestyle such as maintaining a healthy weight, limiting alcohol and HRT. Indeed, since lifestyle factors are the main risk factors for breast cancer, all women should maintain healthy lifestyle habits to reduce their risk, irrespective of family history
PHG Foundation | Genetic and environmental factors linked with breast cancer