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Old 06-04-2010, 12:23 PM   #1
Hopeful
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Join Date: Aug 2006
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Breast Cancer: Environmental Risks Don't Interact With Gene Risks

Elsevier Global Medical News. 2010 Jun 1, MA Moon

Environmental factors known to affect breast cancer risk do not appear to interact with common gene variants that convey a small increased risk of breast cancer, according to a study published online June 2 in the Lancet.

Breast cancer risk is related to both environmental factors and genetic factors, but little is known about how the two types of factors interact. This study examined 10 environmental factors - all of them reproductive, behavioral, or anthropometric factors known to raise breast cancer risk - to assess whether they influenced the small risks conveyed by 12 common genetic variants.

"And the answer is that they do not," said Dr. Ruth C. Travis of the cancer epidemiology unit, University of Oxford (England), and her associates. This lack of interaction means that environmental and genetic factors increase breast cancer risk independently, the investigators noted.

The study assessed 12 single nucleotide polymorphisms (SNPs) that are carried by many women but convey only a small risk of breast cancer; it did not include the much rarer susceptibility genes such as BRCA1 and BRCA2 that convey a high risk of breast cancer but are carried by relatively few women.

The investigators used data collected in the Million Women Study to examine this relationship. In an editorial comment accompanying this report, Dr. Steven A. Narod of Women's College Research Institute, Toronto, explained, "The premise is that, given a large enough sample, if the impact of an environmental factor is conditional on a woman's genotype, the statistical term for the gene-environment interaction should be formally significant."

Findings from this type of analysis could conceivably improve clinicians' ability to predict breast cancer risk, provide clues about as yet undiscovered risk factors for the disease, or lead to identification of new candidate genes, Dr. Narod said (Lancet 2010 June 2[doi:10.1016/S0140-6736(10)60876-8]).

The Million Women Study collected data on 1.3 million middle-aged women in the United Kingdom in 1996-2001 and followed them to track the development of cancer. A subgroup of these subjects participated in a genetic susceptibility study, donating blood samples for genotyping.

In their analysis, Dr. Travis and her colleagues included data on 7,610 of these women who developed incident breast cancer and 10,196 controls who did not. The mean age at diagnosis was 60 years.

The investigators found no interactions between the 12 common SNPs in the DNA of these subjects and any of 10 environmental risk factors (age at menarche, parity, age at first birth, breastfeeding status, menopausal status, age at menopause, use of hormone therapy, body mass index, height, and alcohol consumption).

In the 120 separate statistical comparisons for gene-environment interaction, only 4 yielded a result approaching statistical significance. The strongest interaction was between the CASP8 gene's rs1045485 SNP and alcohol consumption, with relative risk for breast cancer higher in women who reported taking one or more alcohol drinks per day.

Similarly, the interactions between the TNRC9 gene's SNP rs3803662 and age at menopause, the 2q35 gene's SNP rs13387042 and age at menarche, and the 5q gene's SNP rs-30099 and use of hormone therapy were of borderline significance.. "However, in view of the large number of tests done, these could well be chance findings," Dr. Travis and her colleagues said (Lancet 2010 June 2 [doi:10.1016/s0140-6736(10)60636-8]).

"Our findings are largely hypothesis generating," the investigators said. "Tens of thousands of cases will be needed to assess reliably a comprehensive range of biologically plausible gene-environment interactions," they added.

Dr. Narod questioned whether this approach "has been oversold," however, "if attention is limited to the gene variants that have come out of the genome-wide association studies so far and to the known risk factors for breast cancer, we are unlikely to make much progress. The challenge of breast cancer prevention remains and new approaches are needed," he concluded.

This study was funded by Cancer Research UK and the U.K. Medical Research Council. No financial conflicts of interest by the investigators were reported.

Hopeful

Last edited by Hopeful; 06-04-2010 at 12:25 PM..
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