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This Week in the British Journal of Cancer: Jan 31, 2012


In the British Journal of Cancer this week, researchers in Sweden report on the combined effects of low-penetrant SNPs on the risk of breast cancer. The team analyzed 10 previously described breast cancer-associated SNPs in 3,584 breast tumor samples and 5,063 healthy controls. They confirmed significant associations between breast cancer and seven of the 10 SNPs. Analysis of the joint effects of all 10 SNPs in general, and the significant seven in particular, showed a highly significant trend for increased breast cancer risk with an increased number of the alleles in question. "The strongly increasing risk seen when combining many low-penetrant risk alleles supports the polygenic inheritance model of breast cancer," the authors write.

Also in the British Journal of Cancer this week, a team led by researchers at the Cedars-Sinai Medical Center in Los Angeles reports that a natural compound found in cruciferous vegetables, or green-leaf vegetables, could help make ovarian cancer cells more sensitive to treatment with bortezomib. The team analyzed the effects of the compound, I3C, along with bortezomib and cisplatin in several human ovarian cancer cell lines and in a mouse model of ovarian cancer. They found that the combination of bortezomib and I3C led to "profound cell cycle arrest and apoptosis as well as disruptions to multiple pathways, including those regulating endoplasmic reticulum stress, cytoskeleton, chemoresistance and carcinogen metabolism." In addition, the authors write that the combination treatment also sensitized the cancer cells to standard chemotherapeutic agents like cisplatin and carboplatin. "Importantly, in vivo studies demonstrated that co-treatment with I3C and bortezomib significantly inhibited tumor growth and reduced tumor weight compared with either drug alone," the researchers add.

Finally in the British Journal of Cancer this week, researchers in Denmark identify a microRNA cluster that regulates the activity of a bladder cancer proto-oncogene. The team investigated miRNAs regulating the PAI-1 oncogene in a panel of normal bladder urothelial biopsies, superficial bladder tumors, and invasive bladder tumors. They found that the miR-143/-145 cluster is down-regulated in all stages of bladder cancer, and is inversely correlated with PAI-1 expression. "Furthermore, we show that PAI-1 and miR-145 levels may serve as useful prognostic markers for non-muscle-invasive bladder tumors for which accurate progressive outcome is currently difficult to predict," the authors add. "This report provides the first evidence for direct miRNA regulation of PAI-1 in bladder cancer."

The Scan

Self-Reported Hearing Loss in Older Adults Begins Very Early in Life, Study Says

A JAMA Otolaryngology — Head & Neck Surgery study says polygenic risk scores associated with hearing loss in older adults is also associated with hearing decline in younger groups.

Genome-Wide Analysis Sheds Light on Genetics of ADHD

A genome-wide association study meta-analysis of attention-deficit hyperactivity disorder appearing in Nature Genetics links 76 genes to risk of having the disorder.

MicroRNA Cotargeting Linked to Lupus

A mouse-based study appearing in BMC Biology implicates two microRNAs with overlapping target sites in lupus.

Enzyme Involved in Lipid Metabolism Linked to Mutational Signatures

In Nature Genetics, a Wellcome Sanger Institute-led team found that APOBEC1 may contribute to the development of the SBS2 and SBS13 mutational signatures in the small intestine.