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From SNPedia

Geno Mag Summary
(G;G) 0 normal risk
(G;T) 2 1.28x risk for endometrial ovarian cancer; overlaps with rs608995
(T;T) 3 1.42x risk for endometrial ovarian cancer; overlaps with rs608995
ReferenceGRCh38 38.1/142
is asnp
is mentioned by
dbSNP (classic)rs1042838
1000 genomesrs1042838
GWAS Ctlgrs1042838
Max Magnitude3
? (G;G) (G;T) (T;T) 28

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. [PMID 15632380]

A 2010 study [PMID 21148628OA-icon.png] 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 [PMID 18219286OA-icon.png], to that effect a 2010 study found association with endometrial cancer [PMID 20547493OA-icon.png] with same risk haplotypes as the earlier haplotype study on ovarian cancer. A 2014 metastudy [PMID 24197980] 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 [PMID 24943061] 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. [PMID 17609999]

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)".[PMID 19423537OA-icon.png]

[PMID 24943061] Association of the progesterone receptor gene polymorphism (PROGINS) with endometriosis: a meta-analysis.

[PMID 24197980] Progesterone receptor PROGINS and +331G/A polymorphisms confer susceptibility to ovarian cancer: a meta-analysis based on 17 studies.

GWAS snp
PMID [PMID 15632380]
Trait Ovarian cancer
Title Clarifying the PROGINS allele association in ovarian and breast cancer risk: a haplotype-based analysis.
Risk Allele T
P-val 0.022
Odds Ratio 3.23 [1.19-8.75] homozygous
GWAS snp
PMID [PMID 15632380]
Trait Ovarian cancer
Title Clarifying the PROGINS allele association in ovarian and breast cancer risk: a haplotype-based analysis.
Risk Allele T
P-val 0.32
Odds Ratio 1.19 [0.85-1.68] heterozygous

[PMID 16614108] Association of the progesterone receptor gene with breast cancer risk: a single-nucleotide polymorphism tagging approach.

[PMID 17592773] Progesterone receptor polymorphisms and risk of breast cancer: results from two Australian breast cancer studies.

[PMID 17609999] Association of progesterone receptor with migraine-associated vertigo

GWAS snp
PMID [PMID 18219286OA-icon.png]
Trait Ovarian cancer
Title Progesterone receptor variation and risk of ovarian cancer is limited to the invasive endometrioid subtype: results from the Ovarian Cancer Association Consortium pooled analysis.
Risk Allele T
P-val 0.036
Odds Ratio 1.17 [1.01–1.36] per allele

[PMID 18628428OA-icon.png] Polymorphisms in genes involved in sex hormone metabolism, estrogen plus progestin hormone therapy use, and risk of postmenopausal breast cancer.

[PMID 18805939OA-icon.png] Functional genetic polymorphisms and female reproductive disorders: part II--endometriosis.

[PMID 19124506OA-icon.png] Common genetic variation in candidate genes and susceptibility to subtypes of breast cancer.

[PMID 19152063] Polymorphisms in estrogen metabolism and estrogen pathway genes and the risk of miscarriage.

[PMID 19382201OA-icon.png] Association of the progesterone receptor gene with endometrial cancer risk in a Chinese population.

[PMID 19423537OA-icon.png] Five polymorphisms and breast cancer risk: results from the Breast Cancer Association Consortium.

GWAS snp
PMID [PMID 19543528OA-icon.png]
Trait Ovarian cancer
Title Association between common germline genetic variation in 94 candidate genes or regions and risks of invasive epithelial ovarian cancer.
Risk Allele T
P-val 0.0215
Odds Ratio 1.09 [0.73-1.64]

[PMID 19673915] Role of the oestrogen receptor (ESR1 PvuII and ESR1 325 C-->G) and progesterone receptor (PROGINS) polymorphisms in genetic susceptibility to migraine in a North Indian population

GWAS snp
PMID [PMID 20547493OA-icon.png]
Trait Endometrial cancer
Title Genetic variation in the progesterone receptor gene and risk of endometrial cancer: a haplotype-based approach.
Risk Allele T
P-val 0.073
Odds Ratio 1.25 [0.98-1.59]

[PMID 20814185OA-icon.png] Associations of Progesterone Receptor Polymorphisms with Age at Menarche and Menstrual Cycle Length

[PMID 21086036OA-icon.png] Association of progesterone receptor polymorphism with idiopathic recurrent pregnancy loss in Taiwanese Han population

[PMID 21148628OA-icon.png] Progesterone receptor gene variants and risk of endometrial cancer

GWAS snp
PMID [PMID 22633539OA-icon.png]
Trait Ovarian cancer
Title Selected polymorphisms in sex hormone-related genes, circulating sex hormones and risk of endometrial cancer.
Risk Allele T
P-val 0.09
Odds Ratio 1.25 [0.96-1.61]

[PMID 23903878OA-icon.png] Prenatal methylmercury exposure and genetic predisposition to cognitive deficit at age 8 years

[PMID 25494303OA-icon.png] Progesterone Receptor Gene (PROGINS) Polymorphism Correlates with Late Onset of Migraine

[PMID 33000295] Genetic variations in estrogen and progesterone pathway genes in preeclampsia patients and controls in Bavaria.