From Medscape Medical News
Zosia Chustecka
June 2, 2010 — A large analysis of data from the British Million Women Study has found no interaction between environmental risk factors for breast cancer and common low-penetrance susceptibility single-nucleotide polymorphisms (SNPs) that have been associated with breast cancer risk. The new study is published online June 2 in The Lancet.
This study looked at 12 SNPs that have been associated with breast cancer in published genome-wide association studies that have reported a small increase in the risk for breast cancer (relative risk of around 1.2 per allele). The study did not did not investigate BRCA1 and BRCA2 genes, which confer a much higher risk for breast cancer but are found in a relatively smaller number of women.
"We looked at whether lifestyle factors for breast cancer, such as hormone-replacement therapy (HRT), alcohol consumption, and reproductive history, influence the genetic risk. The answer is, they do not," said lead author Ruth Travis, DPhil, from the Cancer Epidemiology Unit at Oxford University, United Kingdom, in a statement.
"This study provides another piece in the jigsaw, helping us to understand how genes and lifestyle affect breast cancer risk," added coauthor Jane Green, MD, from the same unit. "Genes account for only a small proportion of breast cancers and, for most women, the main risk factors remain the lifestyle factors, such as childbearing, use of HRT, obesity, and alcohol consumption. The good news is that some of these are modifiable, so by changing their behavior women can alter their risk of breast cancer."
Testing Gene–Environment Interactions
The researchers used data collected in the Million Women Study, which involved 1.3 million middle-aged women (mean age, 56 years) who had been invited for a routine mammogram from 1996 to 2001. They identified 7610 women who developed breast cancer, and compared them with 10,196 control subjects without the disease.
The team then tested for interactions between 12 polymorphisms that had previously been associated with breast cancer and 10 environmental risk factors for breast cancer (age at menarche, parity, age at first delivery, breast-feeding, menopausal status, age at menopause, use of HRT, body mass index, height, and alcohol consumption). The researchers note that the effects of most of these 10 environmental factors on breast cancer incidence have already been shown to be highly significant for the entire Million Women Study cohort.
There was no convincing evidence for any gene–environment interactions, the team reports.
"Most of the environmental factors are more strongly associated with breast cancer risk than are the genotypic factors we studied" note the researchers. "Current use of HRT is the strongest environmental risk factor in this cohort . . . and the associated relative risks are much greater than for any of the SNPs studied here," they add.
"The function of most of the SNPs is unclear, and future investigations might show them to be only markers of true causal variants," they add.
The authors note that, since they designed their study, another 5 SNPs associated with breast cancer have been identified, although the associated relative risk for breast cancer is not large.
"Of course, there are always more SNPs to study, but to date, none of these seem to contribute to breast cancer in a big way," says Steven Narod, MD, from the Women's College Research Institute in Toronto, Ontario, in an accompanying editorial.
The SNP approach might have been "oversold," he suggests. "Others have come to the conclusion that SNPs, alone or in combination, are not that helpful in predicting cancer risk."
Recently, several experts have expressed concern over the advertising of genetic-susceptibility tests based on SNPs that are sold directly to the general public, as previously reported by Medscape Oncology.
Coming back to the issue of preventive oncology, Dr. Narod says that the crucial question that remains is why having a baby at age 25 should influence the risk for breast cancer at age 65.
"Unfortunately the genes studied here do not provide any new clues," he concludes.
The authors and editorialist have disclosed no relevant financial relationships.
Lancet. Published online June 2, 2010.
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