A mutation associated with a higher incidence and better survival of lung cancer has been identified in Japanese women who do not smoke. In a recent study, the single nucleotide polymorphism (SNP), found in a gene that protects cells from oxidative stress, occurred four times more frequently in women than in men.

Lung cancer is the leading cause of cancer-related deaths in many industrialized countries. Though most deaths are due to long-term exposure to cigarette smoke, nonsmokers account for 10% to 15% of cases.

Toshihisa Ishikawa, PhD, of the RIKEN Center for Life Science Technologies in Saitama, Japan, led the team of researchers. They analyzed the DNA of patients with primary lung cancer and found that nonsmoking Japanese women with two copies of the SNP (-617A) in the NRF2 gene had a markedly higher incidence of adenocarcinoma of the lung, compared with men who were nonsmokers and homozygous.

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Furthermore, both male and female lung cancer patients homozygous for the same SNP in the NRF2 gene survive lung cancer much better. The study was published in PLOS ONE (2013; doi: 10.1371/journal.pone.0073794).

Nuclear factor erythroid-derived 2 (NF-E2)-related factor (NRF2) controls cellular adaptation to oxidants and electrophiles by inducing antioxidation and detoxification genes, and it protects normal cells from external toxic challenges and oxidative stress.

This study also suggests a better prognosis exists for those lung cancer patients who harbor a              SNP (-617A) allele in the NRF2 gene in combination with the wild-type allele of the MDM2 gene.

“This is the first report providing clinical evidence that homozygous alleles for the SNP (-617A), one of the intrinsic genetic polymorphisms in the NRF2 gene, are associated with the overall survival of lung cancer patients,” explained Ishikawa.

“The study strongly suggests that the presence of homozygous alleles for this SNP is a good prognostic biomarker for the assessment of the overall survival chances of patients with adenocarcinoma, as well as a practical tool for personalized cancer therapy,” he concluded.