KLK3 SNP-SNP interactions for prediction of prostate cancer aggressiveness.

Risk classification for prostate cancer (PCa) aggressiveness and underlying mechanisms remain inadequate. Interactions between single nucleotide polymorphisms (SNPs) may provide a solution to fill these gaps. To identify SNP-SNP interactions in the four pathways (the angiogenesis-, mitochondria-, miRNA-, and androgen metabolism-related pathways) associated with PCa aggressiveness, we tested 8587 SNPs for 20,729 cases from the PCa consortium. We identified 3 KLK3 SNPs, and 1083 (P < 3.5 × 10-9) and 3145 (P < 1 × 10-5) SNP-SNP interaction pairs significantly associated with PCa aggressiveness. These SNP pairs associated with PCa aggressiveness were more significant than each of their constituent SNP individual effects. The majority (98.6%) of the 3145 pairs involved KLK3. The 3 most common gene-gene interactions were KLK3-COL4A1:COL4A2, KLK3-CDH13, and KLK3-TGFBR3. Predictions from the SNP interaction-based polygenic risk score based on 24 SNP pairs are promising. The prevalence of PCa aggressiveness was 49.8%, 21.9%, and 7.0% for the PCa cases from our cohort with the top 1%, middle 50%, and bottom 1% risk profiles. Potential biological functions of the identified KLK3 SNP-SNP interactions were supported by gene expression and protein-protein interaction results. Our findings suggest KLK3 SNP interactions may play an important role in PCa aggressiveness.

Alcohol intake patterns for cancer and non-cancer individuals: a population study.

BACKGROUND: Alcohol intake is a leading modifiable cause related to cancer-specific deaths. Various alcohol intake patterns have shown to impact cancer progression differently, however, many studies only evaluated simplified patterns (such as heavy vs. non-heavy drinking) of alcohol intake for cancer survivors. The objective of this study is to provide population-based prevalence of the complex alcohol drinking patterns for cancer survivors, and compare it with that of non-cancer individuals. Additionally, we evaluated the impact of cancer related factors (binary, alcohol-related cancer type, and length of cancer history) to the alcohol intake patterns adjusted for the selected factors. METHODS: A total of 193,197 individuals, including 16,504 cancer survivors, with age ≥18 years old in the 2012-2017 National Health Interview Survey (NHIS) were included in this study. The population-based prevalence of alcohol patterns was estimated. To evaluate cancer related factors associated with the alcohol intake patterns, we applied multinomial logistic models with the appropriate sampling weights and adjusted the selected demographic factors and smoking status. RESULTS: There were 62.1% of cancer survivors and 66.0% of non-cancer individuals who were current alcohol drinkers in the past year. The prevalence of heavy drinking was identical for 5.2% of cancer and non-cancer individuals. For frequent binge drinking, cancer survivors tended to have less frequent binge than non-cancer individuals (2.8% vs. 4.9%). After adjusting for the selected demographic factors and smoking status, the cancer survivors were less likely to have the intermediate level of alcohol intake (light/moderate or occasional binge drinking) compared with non-cancer individuals, but no difference for the excessive alcohol intake (heavy or frequent binge drinking) was observed for those with and without cancer. As for cancer type, those with non-alcohol related cancer tended to be a current drinker compared with those with alcohol-related cancer. Compared with cancer survivors with a short cancer history (2-4 years), survivors with a cancer history of 5-9 years were more likely to be current drinkers after adjusting for the selected factors. Cancer status, alcohol-related cancer type and length of cancer history had no impact on excessive alcohol intake. CONCLUSIONS: In summary, cancer survivors have similar excessive alcohol drinking patterns but were less likely to have the intermediate level of alcohol intake compared to non-cancer individuals. Alcohol intake may enhance cancer progression, interfere with cancer treatments and increase cancer-related mortality. To improve cancer survivors' health, custom alcohol interventions and cessation programs should be conducted to minimize alcohol intake for cancer survivors, especially for excessive alcohol drinkers.