Expressive

rs11059635 (TMEM132C): Chemotherapy Hair Loss

Key takeaways

  • rs11059635 in TMEM132C was identified in one of the first genomic scans for inherited predictors of severe chemotherapy-related hair loss.
  • The study enrolled 303 Japanese breast cancer patients with significant hair loss and 880 without, so findings may not apply universally.
  • This variant is a suggestive secondary finding, not the primary genome-wide significant hit in the study, meaning evidence remains preliminary.
  • The alternate allele is linked to reduced TMEM132C expression in tibial nerve tissue, providing a possible molecular clue.

Key takeaways

  • rs11059635, located within the TMEM132C gene (transmembrane protein 132C), was identified in one of the first genomic scans for inherited predictors of severe chemotherapy-related hair loss.
  • The study enrolled 303 Japanese breast cancer patients who developed significant hair loss and 880 who did not, so findings may not apply universally across ancestral populations.
  • This variant is a suggestive finding from subgroup analyses, not the primary genome-wide significant hit in the study, meaning evidence remains preliminary.
  • The alternate allele is linked to reduced TMEM132C expression in tibial nerve tissue and reduced ENSG00000297923 expression in testicular tissue, providing possible molecular clues.

What the research says A 2014 case-control genome-wide association study (GWAS) - a method that simultaneously scans large numbers of genetic variants across the genome - by Chung et al. examined chemotherapy-induced grade 2 alopecia (significant or complete hair loss) in breast cancer patients enrolled through BioBank Japan, a network of 66 hospitals. Comparing 303 individuals who developed grade 2 alopecia against 880 who did not after receiving conventional chemotherapy, the study identified rs11059635 in TMEM132C among variants with suggestive associations detected in subgroup analyses. The primary genome-wide significant finding was a separate variant, rs3820706 in CACNB4 (calcium channel voltage-dependent subunit beta 4, on chromosome 2q23), with an odds ratio of 3.71 (P = 8.13 × 10^-9); rs11059635 represents a secondary, suggestive finding and did not reach the same significance threshold. Using a weighted genetic risk scoring (wGRS) system that combined multiple associated variants, patients in the highest cumulative risk group had 443 times higher odds of antimicrotubule agent-induced alopecia than those in the lowest group - though this figure reflects the combined score across multiple variants, not rs11059635 in isolation. GTEx v11 eQTL data indicate the alternate allele of this variant is associated with reduced expression of TMEM132C in tibial nerve and reduced expression of ENSG00000297923 in testicular tissue GTEx Portal.

Reported associations

  • Chemotherapy-induced grade 2 alopecia (suggestive): rs11059635 in TMEM132C appeared among suggestive associations in subgroup analyses of breast cancer patients receiving chemotherapy; a specific p-value or effect size for this variant alone is not reported in the available study text.
  • TMEM132C expression in tibial nerve: The alternate allele is associated with reduced TMEM132C expression in tibial nerve tissue (GTEx v11, p = 8.6 × 10^-5) GTEx Portal.
  • ENSG00000297923 expression in testicular tissue: The alternate allele is associated with reduced expression of ENSG00000297923 in testis (GTEx v11, p = 8.5 × 10^-¹¹) GTEx Portal.

Evidence quality The alopecia association rests on a single case-control GWAS of 303 cases and 880 controls, all of Japanese ancestry through BioBank Japan. rs11059635 appears to be a suggestive secondary finding from subgroup analyses rather than a primary genome-wide significant result; no specific p-value or odds ratio for this variant is available in the provided data. The exclusively Japanese sample limits generalizability to other ancestral populations, and no independent replication cohort is described. The GTEx v11 eQTL associations - tibial nerve (p = 8.6 × 10^-5) and testis (p = 8.5 × 10^-¹¹) - provide mechanistic signals at moderate to strong significance levels, but do not establish clinical relevance for the hair-loss phenotype. Overall, evidence for this variant's role in chemotherapy-induced alopecia should be considered preliminary.

Tissue-specific expression effects

  • TMEM132C: The alternate allele is associated with reduced expression in tibial nerve tissue GTEx Portal.
  • ENSG00000297923: The alternate allele is associated with reduced expression in testicular tissue GTEx Portal.

Lifestyle considerations No lifestyle considerations on file for this variant.

Frequently asked questions

What is the TMEM132C gene?

TMEM132C encodes a transmembrane protein, meaning a protein that spans the cell membrane. Its specific role in hair biology or chemotherapy response has not been well characterized in published research.

Is rs11059635 linked to hair loss from chemotherapy?

A genome-wide association study found rs11059635 near TMEM132C among variants with suggestive links to severe chemotherapy-induced hair loss in breast cancer patients. This association is preliminary and has not been independently replicated in the available evidence.

How strong is the evidence connecting rs11059635 to chemotherapy alopecia?

Evidence is preliminary. The variant appeared as a suggestive association in a single study of Japanese breast cancer patients and did not reach genome-wide significance on its own. Independent replication in larger or more diverse populations is needed before drawing firm conclusions.

What does it mean that this variant affects gene expression in nerve tissue?

GTEx data show the alternate allele is associated with modestly reduced TMEM132C expression in tibial nerve. This points to a possible molecular mechanism but does not establish a direct pathway between that expression change and hair loss.

What is chemotherapy-induced alopecia?

Chemotherapy-induced alopecia is hair loss caused by cytotoxic chemotherapy drugs. It typically begins one to two weeks after treatment starts and can result in complete hair loss, with regrowth generally occurring after treatment ends.