What you carry at this position in your DNA and what research says about it.
Chemotherapy Response: 5/10 evidence, 36 publications.
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Sample genotype (not yours): G/G
Better Response to Platinum Chemotherapy
Carrying two copies of the G allele is associated with a more favorable response to platinum-based chemotherapy drugs. It is also considered a completely benign, typical variant for DNA repair disorders.
What this genotype means: Favorable response to platinum-based chemotherapy; Typical DNA repair capacity; No elevated risk for xeroderma pigmentosum.
Sample genotype (not yours): C/C
Typical Chemotherapy Response and Cancer Risk
Carrying two copies of the C allele is associated with a typical response to platinum-based chemotherapy and typical cancer risk. This genotype is considered benign and does not cause severe DNA repair disorders.
What this genotype means: Typical response to platinum-based chemotherapy; Typical baseline DNA repair capacity; No elevated risk for xeroderma pigmentosum.
Sample genotype (not yours): G/C
Carrying one copy of the C allele is associated with a typical response to platinum-based chemotherapy and typical cancer risk. This genotype is considered benign and does not cause severe DNA repair disorders.
Gene function and biological role
Gene Function: The ERCC5 gene, also known as XPG, encodes a structure-specific endonuclease that plays a critical role in the nucleotide excision repair pathway [1]. This pathway is responsible for identifying and repairing DNA damage caused by ultraviolet radiation, chemical mutagens, and certain chemotherapy drugs [2]. When the ERCC5 protein is fully functional, it helps maintain genomic stability by cutting out damaged DNA segments so they can be correctly rebuilt. Deficiencies or severe mutations in this gene can lead to rare genetic disorders characterized by extreme sensitivity to sunlight and high cancer risk.
Variant Impact: The rs17655 variant represents a missense mutation in the ERCC5 gene, resulting in an amino acid substitution from aspartate to histidine at position 1104 of the protein. This change, often referred to as Asp1104His, occurs in a region of the protein that may influence its interaction with other DNA repair factors [1]. Although this variant alters the amino acid sequence, clinical databases classify it as benign for severe genetic repair syndromes. However, the variation can influence how efficiently the cell repairs DNA damage induced by platinum-based chemotherapy agents [2].
Key Insight: Although this variant changes a protein amino acid, clinical databases classify it as completely harmless for severe DNA repair diseases.
Location: ERCC5. Chromosome 13 · 13q33.1 · 102.9 Mb
Estimated prevalence by population
Global 49.7%; European 61.4%; African 30.0%; East Asian 25.8%; South Asian 57.3%; Americas 50.2%; Ashkenazi 52.8%; Finnish 57.8%; Middle Eastern 46.3%; Amish 67.1%.
Estimated GG genotype frequency.
Global 40.0%; European 33.9%; African 49.6%; East Asian 50.0%; South Asian 36.8%; Americas 41.3%; Ashkenazi 39.7%; Finnish 36.5%; Middle Eastern 43.5%; Amish 29.6%.
Estimated GC genotype frequency.
Global 10.3%; European 4.7%; African 20.5%; East Asian 24.2%; South Asian 5.9%; Americas 8.5%; Ashkenazi 7.5%; Finnish 5.8%; Middle Eastern 10.2%; Amish 3.3%.
Estimated CC genotype frequency.
Showing effects for G/G genotype
Pharmacogenomics
Chemotherapy Response
Chemotherapy Response. Evidence: 5/10. Source: PMID 22158331. Stronger Response.
Rare Genetic Disorders
Inherited Metabolic Disorders
Xeroderma Pigmentosum. Evidence: 7/10. Typical Risk.
Cancer & Oncology
Breast Cancer
Breast Cancer. Evidence: 4/10. Source: PMID 25644244. Typical Risk.
Lung Cancer
Lung Cancer. Evidence: 4/10. Source: PMID 17299578. Typical Risk.
Prostate Cancer
Prostate Cancer. Evidence: 3/10. Source: PMID 30123346. Typical Risk.
Brain & Nervous System Cancers
Glioma. Evidence: 4/10. Source: PMID 26843108. Typical Risk.
Showing effects for C/C genotype
Chemotherapy Response. Evidence: 5/10. Source: PMID 22158331. Typical Response.
Showing effects for G/C genotype
What this genotype means for the people who carry it
Sample genotype: GG (Homozygous)
Having the G/G genotype means possessing two copies of the reference aspartate-encoding allele. Research indicates that individuals with this genotype often show a better therapeutic response when treated with platinum-based chemotherapy, such as cisplatin or carboplatin [1]. This may be because the reference ERCC5 protein maintains optimal DNA repair dynamics, allowing cells to process chemotherapy-induced damage in a way that correlates with improved clinical outcomes [2]. In contrast, several large-scale studies and meta-analyses have evaluated this variant's role in cancer susceptibility, finding no consistent increase in the risk of developing breast, lung, or prostate cancers [3] [4]. Furthermore, clinical databases confirm that this common genotype is entirely harmless and does not cause severe DNA repair deficiency syndromes like xeroderma pigmentosum.
Favorable response to platinum-based chemotherapy; Typical DNA repair capacity; No elevated risk for xeroderma pigmentosum.
Sample genotype: CC (Homozygous)
Having the C/C genotype means carrying two copies of the variant C allele, which encodes histidine at position 1104. This genotype is associated with a typical response to platinum-based chemotherapy drugs, lacking the slightly enhanced response seen in G/G carriers [1]. Despite the amino acid change, extensive clinical data confirms that this genotype is entirely benign and does not cause severe DNA repair disorders like xeroderma pigmentosum. Multiple meta-analyses have investigated whether this homozygous variant increases susceptibility to common malignancies, concluding that there is no consistent or strong association with breast, lung, or prostate cancer risks [2] [3] [4]. The body's nucleotide excision repair pathway remains functional, allowing normal processing of DNA damage from environmental factors like sunlight [5]. Therefore, this genotype represents a normal, benign genetic variation.
Typical response to platinum-based chemotherapy; Typical baseline DNA repair capacity; No elevated risk for xeroderma pigmentosum.
Sample genotype: GC (Heterozygous)
Possessing the G/C genotype means carrying one reference G allele and one variant C allele. Individuals with this heterozygous genotype generally exhibit a typical response to platinum-based chemotherapy regimens [1]. While some individual studies have explored whether the C allele alters DNA repair efficiency, comprehensive meta-analyses show no significant overall impact on the risk of developing breast or lung cancers [2] [3]. Clinical evaluations have also confirmed that this variant is completely benign and does not contribute to the development of rare, severe DNA repair syndromes such as xeroderma pigmentosum. The presence of one histidine-encoding allele does not compromise the body's baseline ability to repair daily DNA damage from environmental sources like UV light [4]. Consequently, this genotype is considered a neutral genetic variation with no major negative health implications.
Variants with shared genetic architecture
rs1047768 · ERCC5 Gene · Chr 13 · DNA Repair and Cancer Risk
rs751402 · BIVM-ERCC5 Gene · Chr 13 · DNA Repair and Cancer Risk
rs3219489 · MUTYH Gene · Chr 1 · Colorectal Cancer Risk
DNA-damage response gene polymorphisms and therapeutic outcomes in ovarian cancer.
Polymorphisms in ERCC2 and ERCC5 and Risk of Prostate Cancer: A Meta-Analysis and Systematic Review.
Content updated August 2026.
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