Rs1042838

Minor allele (T) of this SNP uniquely identifies what is known as the PROGINS allele in the progresterone receptor gene PGR.

Two SNP's tagging a partial haplotype of the PGR gene were associated with an increased risk of ovarian cancer among homozygous carriers as compared with noncarriers: rs1042838 (PROGINS allele; odds ratio [OR] = 3.23, 95% confidence interval [CI] = 1.19 to 8.75, P = .022) and rs608995 (minor allele; OR = 3.10, 95% CI = 1.63 to 5.89, P<.001). The study suggest the effect is likely entirely due to rs608995, whose minor allele was almost always seen with PROGINS allele. For rs1042838, the risk allele in orientation to the corresponding dbSNP entry is (T). Subsequent studies have not replicated this high odds ratio, nor the apparent recessive model in this study. The small number of homozygous carriers in the study probably explains this outlier.

A 2010 study of 2888 cases and 4483 controls could not reproduce the association of this SNP with ovarian cancer, even adjusting for ethnicity and BMI. The study concludes their sample size had >90% power to detect OR 1.3 for this SNP, so if an effect exists it must be quite small. A pooled analysis of 4788 ovarian cancer cases and 7614 controls in 2008 suggested that PROGINS risk is limited to invasive endometrioid subtype, to that effect a 2010 study found association with endometrial cancer with same risk haplotypes as the earlier haplotype study on ovarian cancer. A 2014 metastudy however did find association between PROGINS and ovarian cancer, but statistically significant only for Caucasians, those having never used oral contraceptives, and serous (endometrial) cancers, while another meta-study  looking at endometrial cancer specifically found association (OR 1.52-2.72, p = 0.0008-0.03) among European women in particular.

This SNP has also been reported to be associated with migraine-associated vertigo (p = 0.0007). SNPs in genes involved in female hormonal pathways have been a subject of particular interest in the study of migraines because females appear to be more prone to migraines than males.

Previous studies had suggested that the minor allele of this SNP might also influence breast cancer. However, a 2009 European study of 30,000 breast cancer cases, compared to 30,000 controls, found no association, or as they put it, "persuasive evidence against an overall association between invasive breast cancer risk and (this SNP)".

Association of the progesterone receptor gene polymorphism (PROGINS) with endometriosis: a meta-analysis.

Progesterone receptor PROGINS and +331G/A polymorphisms confer susceptibility to ovarian cancer: a meta-analysis based on 17 studies.

Association of progesterone receptor with migraine-associated vertigo

Five polymorphisms and breast cancer risk: results from the Breast Cancer Association Consortium.