What you carry at this position in your DNA and what research says about it.
Skin Cancer Risk: 8/10 evidence, 67 publications.
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Sample genotype (not yours): T/T
Lower Skin Cancer Risk but Higher Cataract Risk
This genotype is associated with a reduced risk of developing skin cancer. However, it may increase susceptibility to age-related cataracts and lead to a poorer response to certain chemotherapy drugs.
What this genotype means: Reduced risk of basal and squamous cell skin cancers; Increased susceptibility to age-related cataracts; Poorer efficacy with platinum-based chemotherapy.
Sample genotype (not yours): C/C
Higher Skin Cancer Risk but Better Chemotherapy Response
This genotype is linked to an increased risk of skin cancer. On the positive side, it is associated with a lower risk of cataracts and a more favorable response to several chemotherapy treatments.
What this genotype means: Increased risk of basal cell skin cancer; Lower susceptibility to age-related cataracts; Improved response to platinum-based chemotherapy and fluorouracil.
Sample genotype (not yours): T/C
Increased Skin Cancer Risk
Having one copy of each allele is associated with an elevated risk of skin cancer. It also correlates with a mixed or poorer response to certain chemotherapy regimens.
What this genotype means: Elevated risk of basal cell skin cancer; Slightly increased risk of age-related cataracts; Suboptimal response to fluorouracil and platinum drugs.
Gene function and biological role
Gene Function: The XRCC1 gene encodes the X-ray repair cross-complementing protein 1, which plays a vital 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 DNA damage, leading to genomic instability and an increased risk of cellular mutations [1]. The protein complexes with other key enzymes, including DNA ligase III and DNA polymerase beta, to coordinate the repair process [1].
Variant Impact: The rs25487 variant is a missense mutation in the XRCC1 gene that changes the amino acid at codon 399 from glutamine to arginine [2]. This change alters the structure of the BRCT1 domain, which is crucial for interacting with other DNA repair proteins [1]. As a result, the variant affects the overall efficiency of DNA repair in response to cellular stress [1]. This single nucleotide change has been widely studied for its dual impact on cancer susceptibility and response to chemotherapy agents [3].
Key Insight: This variant presents a fascinating genetic trade-off where the genotype that protects against skin cancer actually increases the risk of cataracts and reduces chemotherapy effectiveness.
Location: XRCC1. Chromosome 19 · 19q13.31 · 43.6 Mb
Estimated prevalence by population
Global 9.2%; European 12.8%; African 2.2%; East Asian 6.8%; South Asian 12.1%; Americas 9.7%; Ashkenazi 16.3%; Finnish 9.3%; Middle Eastern 7.0%; Amish 16.8%.
Estimated TT genotype frequency.
Global 39.4%; European 46.0%; African 25.2%; East Asian 38.6%; South Asian 45.4%; Americas 42.8%; Ashkenazi 48.2%; Finnish 42.4%; Middle Eastern 39.0%; Amish 48.4%.
Estimated TC genotype frequency.
Global 51.4%; European 41.2%; African 72.6%; East Asian 54.5%; South Asian 42.5%; Americas 47.5%; Ashkenazi 35.5%; Finnish 48.4%; Middle Eastern 54.0%; Amish 34.8%.
Estimated CC genotype frequency.
Showing effects for T/T genotype
Cancer & Oncology
Skin Cancer
Skin Cancer. Evidence: 3/10. Source: PMID 22687647. 0.7x Lower Risk.
Pharmacogenomics
Chemotherapy Response
Chemotherapy Response. Evidence: 8/10. Source: PMID 24224851. Poorer Response.
Organ Systems
Vision & Eye Health
Cataract. Evidence: 3/10. Source: PMID 25873778. Increased Risk.
Showing effects for C/C genotype
Skin Cancer. Evidence: 3/10. Source: PMID 22687647. 2x Higher Risk.
Chemotherapy Response. Evidence: 8/10. Source: PMID 24224851. Stronger Response.
Cataract. Evidence: 3/10. Source: PMID 25873778. Typical Risk.
Showing effects for T/C genotype
What this genotype means for the people who carry it
Sample genotype: TT (Homozygous)
Having two copies of the T allele is linked to a significantly lower risk of both basal cell and squamous cell skin cancers [1]. This protective effect is thought to stem from specific DNA repair efficiencies under UV exposure [1]. However, this same genetic profile is associated with an increased susceptibility to developing age-related cataracts [2]. Additionally, clinical studies suggest that individuals with this genotype may experience a poorer response and decreased survival when treated with platinum-based chemotherapies or fluorouracil [3] [4]. This highlights a complex genetic trade-off between cancer prevention and treatment outcomes.
Reduced risk of basal and squamous cell skin cancers; Increased susceptibility to age-related cataracts; Poorer efficacy with platinum-based chemotherapy.
Sample genotype: CC (Homozygous)
Carrying two copies of the C allele is associated with an approximately two-fold increased risk of skin cancer compared to the T/T genotype [1]. This variant form of the XRCC1 protein may have reduced efficiency in repairing UV-induced DNA damage [1]. Conversely, this genotype appears to offer protection against age-related cataracts, showing a lower incidence in clinical cohorts [2]. Furthermore, in oncology settings, patients with this genotype often show a significantly better response to platinum-based chemotherapies and fluorouracil, alongside a decreased risk of treatment-induced neuropathy [3] [4].
Increased risk of basal cell skin cancer; Lower susceptibility to age-related cataracts; Improved response to platinum-based chemotherapy and fluorouracil.
Sample genotype: TC (Heterozygous)
Carrying one T allele and one C allele is linked to an increased susceptibility to skin cancer, similar to the C/C genotype [1]. This heterozygous state is associated with a roughly two-fold higher risk of basal cell carcinoma compared to the protective T/T genotype [1]. In addition, individuals with this genotype may have an increased risk of developing age-related cataracts [2]. When undergoing chemotherapy, studies indicate a generally poorer response to platinum-based drugs and fluorouracil, along with an increased risk of side effects like nausea [3] [4].
Elevated risk of basal cell skin cancer; Slightly increased risk of age-related cataracts; Suboptimal response to fluorouracil and platinum drugs.
Variants with shared genetic architecture
rs1799782 · XRCC1 Gene · Chr 19 · Cancer Risk
rs25489 · XRCC1 Gene · Chr 19 · DNA Repair and Cancer Risk
rs11170164 · KRT5 Gene · Chr 12 · Skin Cancer Risk
XRCC1 and XPD genetic polymorphisms and susceptibility to age-related cataract: a meta-analysis.
Content updated August 2026.
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