Gallbladder disease (GBD) is a highly prevalent condition; however, little is known about potential differences in risk factors by sex and ethnicity/race. Our aim was to evaluate dietary, reproductive and obesity-related factors and GBD in multiethnic populations. We performed a prospective analysis from the Multiethnic Cohort study who self-identified as non-Hispanic White (n = 32,103), African American (n = 30,209), Japanese (n = 35,987), Native Hawaiian (n = 6942) and Latino (n = 39,168). GBD cases were identified using Medicare and California hospital discharge files (1993–2012) and self-completed questionnaires. We used exposure information on the baseline questionnaire to identify exposures of interest. Associations were estimated by hazard ratios and 95% confidence intervals using Cox models adjusted for confounders. After a median 10.7 years of follow-up, there were 13,437 GBD cases. BMI over 25 kg/m2, diabetes, past and current smoking, red meat consumption, saturated fat and cholesterol were significant risk factors across ethnic/racial populations (p-trends < 0.01). Protective factors included vigorous physical activity, alcohol use, fruits, vegetables and foods rich in dietary fiber (p-trends < 0.01). Carbohydrates were inversely associated with GBD risk only among women and Latinos born in South America/Mexico (p-trend < 0.003). Parity was a significant risk factor among women; post-menopausal hormones use was only associated with an increased risk among White women (estrogen-only: HR = 1.24; 95% CI = 1.07–1.43 and estrogen + progesterone: HR = 1.23; 95% CI = 1.06–1.42). Overall, dietary, reproductive and obesity-related factors are strong risk factors for GBD affecting men and women of different ethnicities/races; however some risk factors appear stronger in women and certain ethnic groups.

Recent genome-wide association studies (GWAS) of Hodgkin lymphoma (HL) have identified associations with genetic variation at both HLA and non-HLA loci; however, much of heritable HL susceptibility remains unexplained. Here we perform a meta-analysis of three HL GWAS totaling 1,816 cases and 7,877 controls followed by replication in an independent set of 1,281 cases and 3,218 controls to find novel risk loci. We identify a novel variant at 19p13.3 associated with HL (rs1860661; odds ratio (OR)=0.81, 95% confidence interval (95% CI)=0.76–0.86, P_combined=3.5 × 10⁻¹⁰), located in intron 2 of TCF3 (also known as E2A), a regulator of B- and T-cell lineage commitment known to be involved in HL pathogenesis. This meta-analysis also notes associations between previously published loci at 2p16, 5q31, 6p31, 8q24 and 10p14 and HL subtypes. We conclude that our data suggest a link between the 19p13.3 locus, including TCF3, and HL risk.

Nodular sclerosing Hodgkin lymphoma (NSHL) is a distinct, highly heritable Hodgkin lymphoma subtype. We undertook a genome-wide meta-analysis of 393 European-origin adolescent/young adult NSHL patients and 3315 controls using the Illumina Human610-Quad Beadchip and Affymetrix Genome-Wide Human SNP Array 6.0. We identified 3 single nucleotide polymorphisms (SNPs) on chromosome 6p21.32 that were significantly associated with NSHL risk: rs9268542 (P = 5.35 × 10⁻¹⁰), rs204999 (P = 1.44 × 10⁻⁹), and rs2858870 (P = 1.69 × 10⁻⁸). We also confirmed a previously reported association in the same region, rs6903608 (P = 3.52 × 10⁻¹⁰). rs204999 and rs2858870 were weakly correlated (r² = 0.257), and the remaining pairs of SNPs were not correlated (r² < 0.1). In an independent set of 113 NSHL cases and 214 controls, 2 SNPs were significantly associated with NSHL and a third showed a comparable odds ratio (OR). These SNPs are found on 2 haplotypes associated with NSHL risk (rs204999-rs9268528-rs9268542-rs6903608-rs2858870; AGGCT, OR = 1.7, P = 1.71 × 10⁻⁶; GAATC, OR = 0.4, P = 1.16 × 10⁻⁴). All individuals with the GAATC haplotype also carried the HLA class II DRB1*0701 allele. In a separate analysis, the DRB1*0701 allele was associated with a decreased risk of NSHL (OR = 0.5, 95% confidence interval = 0.4, 0.7). These data support the importance of the HLA class II region in NSHL etiology.

Interleukin-6 (IL-6) promotes normal plasma cell development and proliferation of myeloma cells in culture. We evaluated IL-6 genotypes and body mass index (BMI) in a case-control study of multiple myeloma and plasmacytoma. DNA samples and questionnaires were obtained from incident cases of multiple myeloma (n = 134) and plasmacytoma (n = 16; plasma cell neoplasms) ascertained from the Los Angeles County population-based cancer registry and from siblings or cousins of cases (family controls, n = 112) and population controls (n = 126). Genotypes evaluated included IL-6 promoter gene single nucleotide polymorphisms (SNP) at positions −174, −572, and −597; one variable number of tandem repeats (−373 A_nT_n); and one SNP in the IL-6 receptor (IL-6rα) gene at position −358. The variant allele of the IL-6 promoter SNP −572 was associated with a roughly 2-fold increased risk of plasma cell neoplasms when cases were compared with family [odds ratio (OR), 1.8; 95% confidence interval (95% CI), 0.7-4.7] or population controls (OR, 2.4; 95% CI, 1.2-4.7). The −373 9A/9A genotype was associated with a decreased risk compared with the most common genotype (OR for cases versus family controls, 0.4; 95% CI, 0.1-1.7; OR for cases versus population controls, 0.3; 95% CI, 0.1-0.9). No other SNPs were associated with risk. Obesity (BMI ≥ 30 kg/m²) increased risk nonsignificantly by 40% and 80% when cases were compared with family controls or population controls, respectively, relative to persons with a BMI of <25 kg/m². These results suggest that IL-6 promoter genotypes may be associated with increased risk of plasma cell neoplasms. (Cancer Epidemiol Biomarkers Prev 2006;15(11):2285–91)

Longitudinal studies of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine-induced immune responses in patients with cancer are needed to optimize clinical care. In a prospective cohort study of 366 (291 vaccinated) patients, we measured antibody levels [anti-spike (IgG-(S-RBD) and anti-nucleocapsid immunoglobulin] at three time points. Antibody level trajectories and frequency of breakthrough infections were evaluated by tumor type and timing of treatment relative to vaccination. IgG-(S-RBD) at peak response (median = 42 days after dose 2) was higher (P = 0.002) and remained higher after 4 to 6 months (P = 0.003) in patients receiving mRNA-1273 compared with BNT162b2. Patients with solid tumors attained higher peak levels (P = 0.001) and sustained levels after 4 to 6 months (P < 0.001) compared with those with hematologic malignancies. B-cell targeted treatment reduced peak (P = 0.001) and sustained antibody responses (P = 0.003). Solid tumor patients receiving immune checkpoint inhibitors before vaccination had lower sustained antibody levels than those who received treatment after vaccination (P = 0.043). Two (0.69%) vaccinated and one (1.9%) unvaccinated patient had severe COVID-19 illness during follow-up. Our study shows variation in sustained antibody responses across cancer populations receiving various therapeutic modalities, with important implications for vaccine booster timing and patient selection.Significance: Long-term studies of immunogenicity of SARS-CoV-2 vaccines in patients with cancer are needed to inform evidence-based guidelines for booster vaccinations and to tailor sequence and timing of vaccinations to elicit improved humoral responses.