What you carry at this position in your DNA and what research says about it.
DNA Repair and Cancer Risk: 3/10 evidence, 22 publications.
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Sample genotype (not yours): C/C
Typical DNA Repair and Baseline Cancer Risk
Two copies of the common C allele provide fully functional XRCC1 protein and typical DNA repair capacity. This genotype is associated with baseline risks for breast, thyroid, and bladder cancers.
What this genotype means: Efficient DNA base excision repair; Baseline risk for breast and thyroid cancers; Typical tolerance to radiation therapy.
Sample genotype (not yours): C/T
Typical DNA Repair with Minor Radiotherapy Sensitivity
Carrying one copy of the T variant does not significantly raise breast cancer risk but may slightly alter radiation sensitivity. DNA repair capacity remains largely sufficient for daily environmental exposures.
What this genotype means: Slightly reduced DNA repair efficiency; Typical baseline breast cancer risk; Possible increased sensitivity to radiation therapy.
Sample genotype (not yours): T/T
Reduced DNA Repair and Elevated Cancer Risk
Two copies of the T variant significantly reduce DNA repair efficiency. This genotype is linked to a higher risk of breast cancer and increased sensitivity to radiation.
What this genotype means: Impaired DNA base excision repair; Elevated risk of breast and thyroid cancers; Higher susceptibility to radiotherapy side effects.
Gene function and biological role
Gene Function: The XRCC1 gene encodes the X-ray repair cross-complementing protein 1, which plays an essential role in the base excision repair pathway [1]. This pathway is responsible for fixing single-strand DNA breaks caused by radiation, reactive oxygen species, and environmental toxins [1]. Without functional XRCC1, cells accumulate genetic damage, leading to genomic instability and an increased risk of uncontrolled cell division [2]. Research shows that complete loss of XRCC1 function is embryonic lethal in animal models, highlighting its critical role in cellular survival [2]. Common variations in this gene can alter its interaction with other repair enzymes, subtly modifying an individual's DNA repair capacity [1] [2].
Variant Impact: The rs25489 variant, also known as p.Arg280His, is a missense mutation in exon 9 of the XRCC1 gene that replaces the amino acid arginine with histidine [1]. This non-conservative amino acid substitution occurs in a region critical for protein-protein interactions, which reduces the overall efficiency of base excision repair [1]. Individuals carrying the variant allele may experience slower clearance of DNA damage, making their cells more vulnerable to mutations [1]. While the variant is relatively rare globally, its frequency varies significantly across different ancestral populations [3]. Understanding this genetic change helps clarify individual differences in cancer susceptibility and sensitivity to radiation therapies [1] [3].
Key Insight: The rs25489 variant alters a highly conserved amino acid in the XRCC1 protein, directly lowering the cell's ability to repair DNA damage from radiation and chemical exposures.
Location: XRCC1. Chromosome 19 · 19q13.31 · 43.6 Mb
Estimated prevalence by population
Global 90.0%; European 91.0%; African 93.9%; East Asian 81.6%; South Asian 81.7%; Americas 84.1%; Ashkenazi 88.7%; Finnish 86.4%; Middle Eastern 67.7%; Amish 96.1%.
Estimated CC genotype frequency.
Global 9.7%; European 8.8%; African 6.0%; East Asian 17.5%; South Asian 17.4%; Americas 15.2%; Ashkenazi 11.0%; Finnish 13.1%; Middle Eastern 29.1%; Amish 3.9%.
Estimated CT genotype frequency.
Global 0.3%; European 0.2%; African 0.1%; East Asian 0.9%; South Asian 0.9%; Americas 0.7%; Ashkenazi 0.3%; Finnish 0.5%; Middle Eastern 3.1%; Amish < 0.1%.
Estimated TT genotype frequency.
Showing effects for C/C genotype
Cancer & Oncology
Breast Cancer
Breast Cancer. Evidence: 3/10. Source: PMID 18188695. Typical Risk.
Cancer Prognosis & Treatment Outcome
Radiotherapy Sensitivity. Evidence: 3/10. Source: PMID 18582155. Typical Sensitivity.
Thyroid & Endocrine Cancers
Thyroid Cancer. Evidence: 3/10. Source: PMID 29552790. Typical Risk.
Urologic Cancers
Bladder Cancer. Evidence: 3/10. Source: PMID 25715450. Typical Risk.
Showing effects for C/T genotype
Radiotherapy Sensitivity. Evidence: 3/10. Source: PMID 18582155. Increased Sensitivity.
Thyroid Cancer. Evidence: 3/10. Source: PMID 29552790. Slightly Higher Risk.
Bladder Cancer. Evidence: 3/10. Source: PMID 25715450. Slightly Higher Risk.
Showing effects for T/T genotype
Breast Cancer. Evidence: 3/10. Source: PMID 18188695. ~4.7x Higher Risk.
What this genotype means for the people who carry it
Sample genotype: CC (Homozygous)
Having the C/C genotype means possessing two copies of the reference allele, which encodes the standard arginine amino acid at position 280 of the XRCC1 protein. This structure allows the protein to interact optimally with other base excision repair enzymes, maintaining efficient repair of single-strand DNA breaks [1]. Population studies show that individuals with this genotype do not experience the elevated breast cancer risks observed in variant homozygotes [1]. Additionally, this genotype is associated with typical tissue tolerance during radiation treatments, showing lower rates of adverse side effects like erectile dysfunction after prostate irradiation compared to variant carriers [2]. Overall, this represents the most common and genetically stable baseline across all studied populations.
Efficient DNA base excision repair; Baseline risk for breast and thyroid cancers; Typical tolerance to radiation therapy.
Sample genotype: CT (Heterozygous)
Possessing the heterozygous C/T genotype means one copy of the XRCC1 gene produces the standard protein, while the other produces the variant histidine form [1]. While this single variant copy does not significantly elevate the risk of breast cancer, some clinical studies suggest it may subtly influence tissue sensitivity to ionizing radiation [1] [2]. For instance, prostate cancer patients with this genotype have shown a higher likelihood of developing radiation-induced side effects, such as erectile dysfunction, compared to those with two copies of the reference allele [2]. Despite this, overall DNA repair capacity remains robust enough to handle typical daily environmental toxins and oxidative stress without a substantial increase in baseline cancer risks [1].
Slightly reduced DNA repair efficiency; Typical baseline breast cancer risk; Possible increased sensitivity to radiation therapy.
Sample genotype: TT (Homozygous)
Having the T/T genotype means both copies of the XRCC1 gene produce the variant histidine protein, which impairs the efficiency of the base excision repair pathway [1]. This reduced repair capacity allows DNA damage from radiation and environmental carcinogens to accumulate more rapidly over time [1]. Consequently, clinical research has linked this genotype to a significantly higher risk of developing breast cancer, with some regional studies reporting up to a 4.6-fold increase in susceptibility [1]. Furthermore, the lack of highly efficient DNA repair makes healthy tissues more vulnerable to damage during medical radiation therapies, increasing the likelihood of severe treatment-related side effects [2]. Maintaining healthy lifestyle habits and avoiding environmental carcinogens like tobacco smoke is particularly relevant for individuals with this genetic profile [1].
Impaired DNA base excision repair; Elevated risk of breast and thyroid cancers; Higher susceptibility to radiotherapy side effects.
Variants with shared genetic architecture
rs25487 · XRCC1 Gene · Chr 19 · Skin Cancer Risk
rs1799782 · XRCC1 Gene · Chr 19 · Cancer Risk
rs180177132 · PALB2 Gene · Chr 16 · Hereditary Cancer Risk
Content updated August 2026.
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