Association of a functional polymorphism (Gln261Arg) in 12-lipoxygenase with breast cancer

Abstract

The overexpression of arachidonyl lipoxygenase-12 (ALOX12) in breast cancer has been reported. Hence, we examined whether a non-synonymous polymorphism of ALOX12 (mRNA, A835G; Gln261Arg) is associated with breast cancer in females. The polymorphism was detected in genomic DNA by PCR-RFLP. The association between the A835G polymorphism and breast cancer risk was measured by odds ratio (OR) with 95% confidence intervals (CIs) using Fisher's exact test, and differences were considered significant at p<0.05. The frequencies of AA (wild-type), GG (homozygous variant) and AG (heterozygous variant) were 59.5, 0.9 and 39.6% in the controls, and 39.3, 2.5 and 58.2% in the breast cancer cases, respectively. The frequency of the AG genotype was higher in the patients compared to the controls (p<0.0014). The frequency of the GG variant was 2.5 and 0.9% in the cancer subjects and controls, respectively. The relative risk of breast cancer was 2 times greater (OR=2.227) at 95% CI when compared to the relative risk of the heterozygous variant. For the GG genotype, the risk was 4 times greater (OR=4.125) at 95% CI than that of the controls, suggesting a positive association of the AG genotype with the occurrence of breast cancer. The frequencies of the polymorphism were different in different populations. The Arg/Gln and Arg/Arg variants were associated with an increased risk of breast cancer, and the frequencies of the variants differed considerably among various populations. The identification of a gene with links to breast cancer may impact screening, diagnosis and drug development.

Figure 1.

Lanes 1–8 are PCR products of the ALOX12 gene obtained from breast cancer patients. The unnumbered lane (adjacent to lane number 8) is the 100-bp DNA ladder. PCR yielded an amplicon of the expected size (187 bp) and was devoid of any non-specific amplification.

Figure 2.

Lanes 1–3, 5, 7 and 8 are of AG genotype, lane 4 is of GG genotype and lane 6 is of AA genotype. The unnumbered lane (adjacent to lane 8) is the 50-bp DNA ladder.

Figure 3.

Validation of the ALOX12 polymorphism (A835G; Arg261Gln) by sequencing. The sample sequence was compared to Homo sapiens arachidonate 12-lipoxygenase mRNA (ALOX12; Ref., NM 000697.2; gene ID, 239 ALOX12), using BLAST, NCBI, USA.