Abstract
We previously found that genetic polymorphisms in gene coding for histamine H4 receptors were related to the risk and malignant degree of breast cancer. The roles of polymorphisms in other histamine-related genes, such as histidine decarboxylase (HDC), histamine N-methyltransferase (HNMT) and histamine H3 receptor (HRH3), remain unexplored. The aim of this study is to analyze the clinical associations of polymorphisms in HDC, HNMT and HRH3 with breast cancer. Two hundred and one unrelated Chinese Han breast cancer patients and 205 ethnicity-matched health controls were recruited for case-control investigation. Genomic DNA from the participants was extracted and 5 single nucleotide polymorphisms (SNPs) in HDC, HNMT and HRH3 were genotyped. We found that polymorphisms of HNMT and HRH3 were irrelevant with breast cancer in the present study. However, the T allele of rs7164386 in HDC significantly decreased the risk of breast cancer (adjusted odds ratios [ORs], 0.387; 95% confidence intervals [CIs], 0.208–0.720; P = 0.003). Furthermore, for HDC haplotypes, the CG haplotype of rs7164386-rs7182203 was more frequent among breast cancer patients (adjusted OR, 1.828; 95% CI, 1.218–2.744; P = 0.004) while the TG haplotype was more frequent among health controls (adjusted OR, 0.351; 95% CI, 0.182–0.678; P = 0.002). These findings indicated that polymorphisms of HDC gene were significantly associated with breast cancer in Chinese Han population and may be novel diagnostic or therapeutic targets for breast cancer. Further studies with larger participants worldwide are still needed for conclusion validation.
Highlights
It is gradually recognized that histamine and its related proteins play important roles in many aspects of breast cancer
In the following association analysis, we found that there were no significant associations between breast cancer risk and polymorphisms in histamine N-methyltransferase (HNMT) and HRH3 genotypes before or after adjustment for age, menopausal state and body mass index (BMI) (Table 2) in the present population, which were in accordance with the allele data (Table 3)
As for histidine decarboxylase (HDC) gene, we found that the frequency of the heterozygous variant CT genotype of rs7164386 in breast cancer case group was significantly differed from control group at Bonferroni-corrected P level of 0.01 (0.05/5 single nucleotide polymorphisms (SNPs)) before adjustment for age, menopausal state and BMI and that the difference still remain significant after further adjustment
Summary
It is gradually recognized that histamine and its related proteins (synthesis and catabolic enzymes or different types of receptors) play important roles in many aspects of breast cancer. One of the histamine catabolic enzymes, histamine N-methyltransferase (HNMT), and histamine H3 (HRH3) and H4 (HRH4) receptors were closely involved in proliferation and differentiation of breast cancer according to recent investigations [3,4,5]. These histamine-related proteins may be important diagnostic or therapeutic targets of breast cancer and clarifying their relationships with breast cancer risk and development will be one of the important topics in this field. The associations between polymorphisms of HDC, HNMT, HRH3 and susceptibility to breast cancer are still unknown so far and need to be elucidated
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