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Previous genome-wide association studies among women of European ancestry identified two independent breast cancer susceptibility loci represented by single nucleotide polymorphisms (SNPs) rs13281615 and rs11780156 at 8q24. A fine-mapping study across 2.06 Mb (chr8:127,561,724-129,624,067, hg19) in 55,540 breast cancer cases and 51,168 controls within the Breast Cancer Association Consortium was conducted. Three additional independent association signals in women of European ancestry, represented by rs35961416 (OR = 0.95, 95% CI = 0.93-0.97, conditional p = 5.8 × 10(-6) ), rs7815245 (OR = 0.94, 95% CI = 0.91-0.96, conditional p = 1.1 × 10(-6) ) and rs2033101 (OR = 1.05, 95% CI = 1.02-1.07, conditional p = 1.1 × 10(-4) ) were found. Integrative analysis using functional genomic data from the Roadmap Epigenomics, the Encyclopedia of DNA Elements project, the Cancer Genome Atlas and other public resources implied that SNPs rs7815245 in Signal 3, and rs1121948 in Signal 5 (in linkage disequilibrium with rs11780156, r(2)  = 0.77), were putatively functional variants for two of the five independent association signals. The results highlighted multiple 8q24 variants associated with breast cancer susceptibility in women of European ancestry.

Morning chronotype has been associated with a reduced risk of prostate and breast cancer. However, few studies have examined whether chronotype is associated with digestive tract cancer risk. We conducted a Mendelian randomization (MR) study to assess the associations of chronotype with major digestive tract cancers. A total of 317 independent genetic variants associated with chronotype at the genome‐wide significance level (P < 5 × 10−8) were used as instrumental variables from a genome‐wide meta‐analysis of 449 734 individuals. Summary‐level data on overall and six digestive tract cancers, including esophageal, stomach, liver, biliary tract, pancreatic and colorectal cancers, were obtained from the UK Biobank (11 952 cases) and FinnGen (7638 cases) study. Genetic liability to morning chronotype was associated with reduced risk of overall digestive tract cancer and cancers of stomach, biliary tract and colorectum in UK Biobank. The associations for the overall digestive tract, stomach and colorectal cancers were directionally replicated in FinnGen. In the meta‐analysis of the two sources, genetic liability to morning chronotype was associated with a decreased risk of overall digestive tract cancer (odds ratio [OR] 0.94, 95% confidence interval [CI]: 0.90‐0.98), stomach cancer (OR 0.84, 95% CI: 0.73‐0.97) and colorectal cancer (OR 0.92, 95% CI: 0.87‐0.98), but not with the other studied cancers. The associations were consistent in multivariable MR analysis with adjustment for genetically predicted sleep duration, short sleep, insomnia and body mass index. The study provided MR evidence of inverse associations of morning chronotype with digestive tract cancer, particularly stomach and colorectal cancers. [ABSTRACT FROM AUTHOR]

Evidence on the association between selenium and cancer risk is inconclusive. We conducted a Mendelian randomization study to examine the associations of selenium levels with 22 site‐specific cancers and any cancer. Single nucleotide polymorphisms (SNPs) strongly associated with toenail and blood (TAB) and blood selenium levels in mild linkage disequilibrium (r2 <.3) were used as instrumental variables. Genetic associations of selenium‐associated SNPs with cancer were obtained from the UK Biobank including a total of 59 647 cancer cases and 307 914 controls. Associations with P <.1 in UK Biobank were tested for replication in the FinnGen consortium comprising more than 180 000 individuals. The inverse‐variance weighted method accounting for linkage disequilibrium was used to estimate the associations. Genetically predicted TAB selenium levels were not associated with the risk of the 22 site‐specific cancers or any cancer (all 22 site‐specific cancers). Similarly, we observed no strong association for genetically predicted blood selenium levels. However, genetically predicted blood selenium levels showed suggestive associations with risk of kidney cancer (odds ratio [OR] per one‐unit increase in log‐transformed levels: 0.83; 95% confidence interval [CI]: 0.67‐1.03) and multiple myeloma (OR: 1.40; 95% CI: 1.02‐1.93). The same direction of association for kidney cancer but not for multiple myeloma was observed in FinnGen. In the metaanalysis of UK Biobank and FinnGen, the OR of kidney cancer was 0.83 (95% CI: 0.69‐1.00). Our study suggests that high selenium status may not prevent cancer development. The associations for kidney cancer and multiple myeloma need to be verified in well‐powered studies. [ABSTRACT FROM AUTHOR]

Studies of sleep duration in relation to the risk of site‐specific cancers other than breast cancer are scarce. Furthermore, the available results are inconclusive and the causality remains unclear. We aimed to investigate the potential causal associations of sleep duration with overall and site‐specific cancers using the Mendelian randomization (MR) design. Single‐nucleotide polymorphisms associated with the sleep traits identified from a genome‐wide association study were used as instrumental variables to estimate the association with overall cancer and 22 site‐specific cancers among 367 586 UK Biobank participants. A replication analysis was performed using data from the FinnGen consortium (up to 121 579 individuals). There was suggestive evidence that genetic liability to short‐sleep duration was associated with higher odds of cancers of the stomach (odds ratio [OR], 2.22; 95% confidence interval [CI], 1.15‐4.30; P =.018), pancreas (OR, 2.18; 95% CI, 1.32‐3.62; P =.002) and colorectum (OR, 1.48; 95% CI, 1.12‐1.95; P =.006), but with lower odds of multiple myeloma (OR, 0.47; 95% CI, 0.22‐0.99; P =.047). Suggestive evidence of association of genetic liability to long‐sleep duration with lower odds of pancreatic cancer (OR, 0.44; 95% CI, 0.25‐0.79; P =.005) and kidney cancer (OR, 0.44; 95% CI, 0.21‐0.90; P =.025) was observed. However, none of these associations passed the multiple comparison threshold and two‐sample MR analysis using FinnGen data did not confirm these findings. In conclusion, this MR study does not provide strong evidence to support causal associations of sleep duration with risk of overall and site‐specific cancers. Further MR studies are required. What's new? With the exception of breast cancer, the impact of sleep duration on site‐specific cancer risk remains largely unknown. Here, using Mendelian randomization analysis, the authors investigated the causal role of sleep duration for overall cancer and for 22 site‐specific cancers in more than 367 000 UK Biobank participants. Suggestive associations were detected between certain cancer sites and genetic liability to short or long sleep duration or genetically predicted sleep duration. However, no statistically significant associations were identified between sleep duration and overall or site‐specific cancer risk, indicating that sleep duration does not have a causal influence on cancer. [ABSTRACT FROM AUTHOR]