What you carry at this position in your DNA and what research says about it.
Inflammatory Response and Health: 8/10 evidence, 16 publications.
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Sample genotype (not yours): C/C
Higher Psoriasis Risk but Lower Cancer Risk
This genotype is linked to a higher likelihood of developing psoriasis but offers protective benefits against several cancers.
What this genotype means: Higher risk of psoriasis; Lower risk of several cancers; Better baseline lung function.
Sample genotype (not yours): C/T
Balanced Inflammatory and Cellular Risks
This genotype represents a balanced profile with typical lung function and moderate protection against certain cancers.
What this genotype means: Typical baseline lung function; Moderate protection against certain cancers; Slightly elevated psoriasis risk.
Sample genotype (not yours): T/T
Higher Cancer Risk and Lower Lung Function
This genotype is associated with an increased risk of several cancers and lower lung function, though it protects against psoriasis.
What this genotype means: Higher risk of several cancers; Lower baseline lung function; Lower risk of psoriasis.
Gene function and biological role
Gene Function: The NFKBIA gene encodes the IkappaB-alpha protein, which acts as a critical cellular brake on the NF-kappaB signaling pathway [1]. NF-kappaB is a master regulator of the body's inflammatory response, immune defense, and cell survival mechanisms [2]. Under normal conditions, IkappaB-alpha binds to NF-kappaB and keeps it inactive in the cell's cytoplasm [1]. When inflammatory signals arrive, this inhibitor is degraded, allowing NF-kappaB to enter the nucleus and activate genes that drive inflammation [2]. Variations in this gene can alter the stability of the inhibitor, leading to either unchecked inflammation or altered immune responses [1] [2].
Variant Impact: The rs696 variant is located in the 3 prime untranslated region of the NFKBIA gene, a region crucial for regulating gene expression [1]. This genetic change alters a binding site for microRNAs, specifically miR-449a, which help control how much of the inhibitor protein is produced [1]. The C allele corresponds to more stable gene expression, whereas the T allele is associated with altered mRNA stability and lower inhibitory control over NF-kappaB [1]. Consequently, this single nucleotide change can influence the baseline level of inflammation in various tissues, affecting susceptibility to autoimmune conditions and cellular growth patterns [1] [3].
Key Insight: This variant acts as a genetic dial for the immune system, where the same allele that increases the risk of inflammatory skin conditions like psoriasis also appears to offer protection against certain types of cellular overgrowth and cancers.
Location: NFKBIA. Chromosome 14 · 14q13.2 · 35.4 Mb
Estimated prevalence by population
Global 32.2%; European 38.6%; African 15.2%; East Asian 36.2%; South Asian 32.1%; Americas 43.9%; Ashkenazi 36.0%; Finnish 36.1%; Middle Eastern 27.8%; Amish 62.5%.
Estimated CC genotype frequency.
Global 47.1%; European 47.1%; African 47.5%; East Asian 47.9%; South Asian 49.1%; Americas 44.7%; Ashkenazi 48.0%; Finnish 48.0%; Middle Eastern 49.9%; Amish 33.1%.
Estimated CT genotype frequency.
Global 20.7%; European 14.4%; African 37.3%; East Asian 15.8%; South Asian 18.8%; Americas 11.4%; Ashkenazi 16.0%; Finnish 15.9%; Middle Eastern 22.4%; Amish 4.4%.
Estimated TT genotype frequency.
Showing effects for C/C genotype
Organ Systems
Skin & Hair Conditions
Psoriasis. Evidence: 6/10. Source: PMID 39883516. Increased Risk.
Respiratory Health
Lung Function. Evidence: 6/10. Source: PMID 40374629. Better Function.
Cancer & Oncology
General Cancer Risk
Cancer Susceptibility. Evidence: 3/10. Source: PMID 26488500. Lower Risk.
Cardiovascular & Metabolic
Blood Cell & Iron Traits
White Blood Cell Count. Evidence: 8/10. Source: PMID 32888494. Typical Count.
Pharmacogenomics
Pain Medication Response
Sufentanil Response. Evidence: 5/10. Source: PMID 32606912. Typical Response.
Showing effects for C/T genotype
Psoriasis. Evidence: 6/10. Source: PMID 39883516. Slightly Increased.
Lung Function. Evidence: 6/10. Source: PMID 40374629. Typical Function.
Showing effects for T/T genotype
Psoriasis. Evidence: 6/10. Source: PMID 39883516. Typical Risk.
Lung Function. Evidence: 6/10. Source: PMID 40374629. Lower Function.
Cancer Susceptibility. Evidence: 3/10. Source: PMID 26488500. Increased Risk.
White Blood Cell Count. Evidence: 8/10. Source: PMID 32888494. Higher Count.
Sufentanil Response. Evidence: 5/10. Source: PMID 32606912. Higher Tolerance.
What this genotype means for the people who carry it
Sample genotype: CC (Homozygous)
Carrying two copies of the C allele is associated with an increased susceptibility to psoriasis, an inflammatory skin condition [1]. However, this same genetic profile is linked to a significantly lower risk of overall cancer development, including colorectal and blood cancers, because it maintains robust levels of the NF-kappaB inhibitor [2]. Research also shows that this genotype is associated with better lung function as measured by forced expiratory volume [3]. Electrocardiogram measurements indicate a slightly longer PR interval, which reflects typical cardiac conduction times [4]. Overall, this genotype represents a classic genetic trade-off between inflammatory skin sensitivity and systemic cellular protection.
Higher risk of psoriasis; Lower risk of several cancers; Better baseline lung function.
Sample genotype: CT (Heterozygous)
Carrying one C allele and one T allele generally results in an intermediate inflammatory profile. The presence of the C allele provides a protective effect against overall cancer susceptibility compared to the T/T genotype [1]. Psoriasis risk is only slightly elevated compared to the baseline population [2]. Lung function and white blood cell counts typically fall within the normal, average range [3] [4]. This heterozygous state avoids the higher cancer risks associated with the T/T genotype while also avoiding the maximum psoriasis risk seen in C/C individuals.
Typical baseline lung function; Moderate protection against certain cancers; Slightly elevated psoriasis risk.
Sample genotype: TT (Homozygous)
Carrying two copies of the T allele is linked to a higher risk of developing various cancers, including colorectal and liver malignancies, due to reduced stability of the NF-kappaB inhibitor [1] [2]. This genotype is also associated with lower baseline lung function as measured by forced expiratory volume [3]. On the positive side, these individuals have a lower risk of developing the inflammatory skin condition psoriasis [4]. Additionally, clinical studies suggest that individuals with this genotype may respond less strongly to the pain medication sufentanil after surgery [5].
Higher risk of several cancers; Lower baseline lung function; Lower risk of psoriasis; May respond less strongly to sufentanil for pain relief.
Variants with shared genetic architecture
rs8016947 · NFKBIA Gene · Chr 14 · Psoriasis Risk
rs8904 · NFKBIA Gene · Chr 14 · Blood Pressure
rs2233406 · NFKBIA Gene · Chr 14 · Infection Susceptibility
Common Polymorphisms in the NFKBIA Gene and Cancer Susceptibility: A Meta-Analysis.
The Polygenic and Monogenic Basis of Blood Traits and Diseases.
Content updated August 2026.
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