What you carry at this position in your DNA and what research says about it.
DNA Repair and Cancer Risk: 5/10 evidence, 34 publications.
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Sample genotype (not yours): G/G
Slightly Higher Cancer Risk and Reduced DNA Repair
Two copies of the G allele are associated with a slight increase in susceptibility to certain cancers, particularly lung and bladder cancers. This genotype may also influence how the body responds to specific chemotherapy drugs like cisplatin.
What this genotype means: Slightly increased risk of lung, bladder, and colorectal cancers; Reduced DNA repair efficiency; Higher risk of hearing damage and toxicity during cisplatin chemotherapy.
Sample genotype (not yours): G/T
One copy of the G allele is associated with a minor increase in susceptibility to certain cancers and slightly reduced DNA repair efficiency. This genotype can also influence sensitivity to platinum-based chemotherapy drugs.
What this genotype means: Minor increase in lung and bladder cancer risk; Slightly reduced DNA repair efficiency; Increased risk of cisplatin-induced side effects.
Sample genotype (not yours): T/T
Typical Cancer Risk and Efficient DNA Repair
Two copies of the T allele represent the typical genotype, which is associated with standard DNA repair efficiency and baseline cancer risk. This genotype also indicates a typical response to certain chemotherapy treatments.
What this genotype means: Baseline risk for lung, bladder, and colorectal cancers; Optimal DNA repair efficiency; Standard risk of side effects during cisplatin chemotherapy.
Gene function and biological role
Gene Function: The XPC gene encodes a key protein in the nucleotide excision repair pathway, which is responsible for fixing damaged DNA [1]. This protein acts as a primary sensor that detects bulky DNA damage caused by environmental toxins, such as ultraviolet radiation and chemical carcinogens [2]. Once damage is recognized, the protein recruits other repair factors to correct the errors before they can lead to mutations [1]. Severe, rare mutations in this gene can cause xeroderma pigmentosum, a condition characterized by extreme sensitivity to sunlight and a high risk of skin cancers [3]. However, common variations in the gene typically result in much milder differences in repair efficiency [2].
Variant Impact: The rs2228001 variant represents a missense change in the XPC gene, substituting the amino acid glutamine for lysine at position 939 [1]. This specific change occurs in a domain of the protein that interacts with other essential DNA repair machinery [4]. The substitution alters the protein's structural stability and can slightly reduce its overall ability to repair damaged DNA [2]. While this variant does not cause severe genetic diseases like xeroderma pigmentosum, it is widely studied for its subtle influence on cancer susceptibility and chemotherapy response [1] [5].
Key Insight: Although this variant is linked to minor differences in cancer risk, ClinVar confirms it does not cause the severe genetic disorder xeroderma pigmentosum. The G allele can increase the risk of hearing damage and other toxicities during cisplatin chemotherapy, but may slightly reduce infection risk during doxorubicin treatment.
Location: XPC. Chromosome 3 · 3p25.1 · 14.1 Mb
Estimated prevalence by population
Global 12.8%; European 16.5%; African 7.5%; East Asian 13.2%; South Asian 11.7%; Americas 10.8%; Ashkenazi 21.8%; Finnish 9.0%; Middle Eastern 26.4%; Amish 10.9%.
Estimated GG genotype frequency.
Global 44.9%; European 48.3%; African 39.8%; East Asian 46.3%; South Asian 45.0%; Americas 44.2%; Ashkenazi 49.8%; Finnish 42.0%; Middle Eastern 50.0%; Amish 44.3%.
Estimated GT genotype frequency.
Global 42.3%; European 35.2%; African 52.8%; East Asian 40.6%; South Asian 43.3%; Americas 45.0%; Ashkenazi 28.4%; Finnish 48.9%; Middle Eastern 23.7%; Amish 44.8%.
Estimated TT genotype frequency.
Showing effects for G/G genotype
Cancer & Oncology
Lung Cancer
Lung Cancer. Evidence: 4/10. Source: PMID 23400628. ~1.2x Risk.
Urologic Cancers
Bladder Cancer. Evidence: 4/10. Source: PMID 23400628. Increased Risk.
Colorectal Cancer
Colorectal Cancer. Evidence: 3/10. Source: PMID 23400628. Increased Risk.
General Cancer Risk
DNA Repair Capacity. Evidence: 4/10. Source: PMID 25785113. Reduced Efficiency.
Pharmacogenomics
Chemotherapy Response
Cisplatin Toxicity. Evidence: 5/10. Source: PMID 19434073. Increased Risk.
Showing effects for G/T genotype
Lung Cancer. Evidence: 4/10. Source: PMID 23400628. Slightly Increased.
Bladder Cancer. Evidence: 4/10. Source: PMID 23400628. Slightly Increased.
Colorectal Cancer. Evidence: 3/10. Source: PMID 23400628. Slightly Increased.
DNA Repair Capacity. Evidence: 4/10. Source: PMID 25785113. Slightly Reduced.
Showing effects for T/T genotype
Lung Cancer. Evidence: 4/10. Source: PMID 23400628. Typical Risk.
Bladder Cancer. Evidence: 4/10. Source: PMID 23400628. Typical Risk.
Colorectal Cancer. Evidence: 3/10. Source: PMID 23400628. Typical Risk.
DNA Repair Capacity. Evidence: 4/10. Source: PMID 25785113. Typical Efficiency.
Cisplatin Toxicity. Evidence: 5/10. Source: PMID 19434073. Typical Risk.
What this genotype means for the people who carry it
Sample genotype: GG (Homozygous)
Production of the glutamine form of the XPC protein occurs when two G alleles are present, which has been shown to have reduced DNA repair efficiency [1]. Meta-analyses of numerous clinical studies indicate that this genotype is associated with a modest increase in the risk of developing lung, bladder, and colorectal cancers [2] [3]. The reduced capacity to repair DNA damage means that environmental exposures, such as tobacco smoke or dietary carcinogens, may have a more pronounced impact on cellular health [4]. Additionally, clinical research suggests that this genotype is linked to an increased risk of side effects, including hearing damage and neutropenia, when treated with cisplatin chemotherapy [5]. Conversely, some studies have noted a decreased risk of infection during doxorubicin treatment [6]. Overall, while the risk increase for any individual cancer is small, maintaining healthy lifestyle habits and avoiding known carcinogens is particularly beneficial.
Slightly increased risk of lung, bladder, and colorectal cancers; Reduced DNA repair efficiency; Higher risk of hearing damage and toxicity during cisplatin chemotherapy.
Sample genotype: GT (Heterozygous)
Presence of both the G and T alleles results in a mixture of the glutamine and lysine forms of the XPC protein. This combination leads to a slight reduction in the efficiency of the nucleotide excision repair pathway compared to the typical genotype [1]. Large-scale genetic analyses suggest that this intermediate state carries a very modest increase in the risk of lung and bladder cancers, particularly when combined with environmental exposures like smoking [2] [3]. In the context of cancer treatment, clinical studies have associated this genotype with a higher likelihood of experiencing toxicities, such as hearing damage, during cisplatin chemotherapy [4]. However, it has also been linked to a lower risk of infection during doxorubicin therapy [5]. Because the overall impact on cancer risk is subtle, focusing on standard preventive health measures and avoiding tobacco smoke remains the most effective strategy.
Minor increase in lung and bladder cancer risk; Slightly reduced DNA repair efficiency; Increased risk of cisplatin-induced side effects.
Sample genotype: TT (Homozygous)
Inheriting two copies of the T allele encodes the lysine form of the XPC protein, which maintains optimal function within the nucleotide excision repair pathway [1]. This genotype is considered the baseline or protective state, as it is associated with a lower risk of developing lung, bladder, and colorectal cancers compared to carrying the G allele [2] [3]. The efficient repair of DNA damage helps the body effectively neutralize the effects of environmental carcinogens, such as those found in tobacco smoke or charred meats [4]. In a clinical setting, individuals with this genotype typically experience fewer side effects, such as hearing loss or severe white blood cell drops, when undergoing cisplatin chemotherapy [5]. While this genotype provides standard cellular defense mechanisms, maintaining a healthy lifestyle and avoiding carcinogens remains essential for long-term health.
Baseline risk for lung, bladder, and colorectal cancers; Optimal DNA repair efficiency; Standard risk of side effects during cisplatin chemotherapy.
Variants with shared genetic architecture
rs2228000 · XPC Gene · Chr 3 · Bladder Cancer Risk
rs1799794 · XRCC3 Gene · Chr 14 · Chemotherapy Toxicity
rs267607954 · MSH2 Gene · Chr 2 · Lynch Syndrome Risk
Xeroderma pigmentosum genes and melanoma risk.
Association between six genetic polymorphisms and colorectal cancer: a meta-analysis.
Content updated August 2026.
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