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Background Epidemiological studies have demonstrated a positive association between chronic lymphocytic leukaemia (CLL) and non-melanoma skin cancer (NMSC). We hypothesized that shared genetic risk factors between CLL and NMSC could contribute to the association observed between these diseases. Methods We examined the association between (i) established NMSC susceptibility loci and CLL risk in a meta-analysis including 3100 CLL cases and 7667 controls and (ii) established CLL loci and NMSC risk in a study of 4242 basal cell carcinoma (BCC) cases, 825 squamous cell carcinoma (SCC) cases and 12802 controls. Polygenic risk scores (PRS) for CLL, BCC and SCC were constructed using established loci. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Results Higher CLL-PRS was associated with increased BCC risk (OR4th-quartile-vs-1st-quartile = 1.13, 95% CI: 1.02–1.24, Ptrend = 0.009), even after removing the shared 6p25.3 locus. No association was observed with BCC-PRS and CLL risk (Ptrend = 0.68). These findings support a contributory role for CLL in BCC risk, but not for BCC in CLL risk. Increased CLL risk was observed with higher SCC-PRS (OR4th-quartile-vs-1st-quartile = 1.22, 95% CI: 1.08–1.38, Ptrend = 1.36 × 10–5), which was driven by shared genetic susceptibility at the 6p25.3 locus. Conclusion These findings highlight the role of pleiotropy regarding the pathogenesis of CLL and NMSC and shows that a single pleiotropic locus, 6p25.3, drives the observed association between genetic susceptibility to SCC and increased CLL risk. The study also provides evidence that genetic susceptibility for CLL increases BCC risk.

Cancer has been linked to HIV since the earliest days of the epidemic. The unusually frequent occurrence of Kaposi sarcoma (KS) among men who have sex with men (MSM) in 1981 was a sentinel observation leading to the inclusion of KS in the first AIDS case definition.1,2 More than three decades later, major research investments have led to striking advances in understanding HIV pathogenesis, with antiretroviral therapy (ART) reducing AIDS complications and allowing HIV-infected individuals to experience life expectancy approaching that of persons without HIV.

Weare grateful for the correspondence provided by De Paoli and Carbone1 regarding our recently published Comments and Controversies piece focused on HIV-associated cancers. Their letter provides an important extension of some of the main points articulated in our article. Indeed, we wish to acknowledge our correspondents’ own excellent review also highlighting the complexity and heterogeneity of cancers occurring in the HIV-infected population

BACKGROUND & AIMS: People infected with human immunodeficiency virus (HIV) have an increased risk of some malignancies, but little is known about the effects of infection on risk of cancers of the upper gastrointestinal tract. We evaluated the risks of different histologic and anatomic subtypes of carcinomas and non-Hodgkin lymphomas (NHLs) of the stomach and esophagus in people with acquired immunodeficiency syndrome (AIDS). METHODS: We analyzed data from the HIV/AIDS Cancer Match Study, which links data collected from 1980 to 2007 for 16 US population-based HIV and AIDS and cancer registries. We compared risks of stomach and esophageal malignancies in people with AIDS (N = 596,955) with those of the general population using standardized incidence ratios (SIRs). We assessed calendar trends using Poisson regression. RESULTS: People with AIDS had increased risks of carcinomas of the esophagus (SIR, 1.69; 95% confidence interval [CI], 1.37-2.07; n = 95) and stomach (SIR, 1.44; 95% CI, 1.17-1.76; n = 96). Risk was increased for esophageal adenocarcinoma (SIR, 1.91; 95% CI, 1.31-2.70) and squamous cell carcinoma (SIR, 1.47; 95% CI, 1.10-1.92). People with AIDS had greater risks of carcinomas of the gastric cardia (SIR, 1.36; 95% CI, 0.83-2.11) and noncardia (SIR, 1.53; 95% CI, 1.12-2.05) than the general population. Although most stomach and esophageal NHLs that developed in people with AIDS were diffuse large B-cell lymphomas, these individuals also had an increased risk of stomach mucosa-associated lymphoid tissue lymphoma (SIR, 5.99; 95% CI, 3.19-10.2; n = 13). The incidence of carcinomas remained fairly constant over time, but rates of NHL decreased from 1980 to 2007 (Ptrend < .0001).CONCLUSIONS: People with AIDS are at increased risk for developing esophageal and stomach carcinomas and NHLs. Although the incidence of NHL decreased from 1980 to 2007 as treatments for HIV infection improved, HIV-infected individuals face continued risks of esophageal and stomach carcinomas.

Incidence of post-transplant lymphoproliferative disorder (PTLD) is bimodal, suggesting distinct early-onset and late-onset subtypes. We evaluated differences in risk factors for early-onset and late-onset PTLD in a retrospective cohort study of U.S. kidney transplant recipients using data from the Scientific Registry of Transplant Recipients (N=156,740, 1999–2007). Multivariate hazard ratios (HRs) for risk factors were estimated using proportional hazards models. For early-onset PTLD, significantly increased risk was associated with young age at transplantation (HR 3.97 for 50, respectively, vs. 20–50 years) and non-Hispanic white race/ethnicity (HR 1.77) increased late-onset PTLD risk. The association with young age was weaker for late-onset than early-onset PTLD (p=0.06), and EBV and cytomegalovirus serostatus were not associated with late-onset PTLD risk. These results support somewhat different etiologies for early-onset and late-onset PTLD. For early-onset PTLD, associations with young age and EBV seronegativity highlight the etiologic role of primary EBV infection. For late-onset PTLD, higher risk with older age is consistent with lymphoma patterns in the general population.

BACKGROUND: In Xuanwei County, China, unvented indoor coal burning is strongly associated with increased risk of lung cancer and chronic obstructive pulmonary disease. However, the impact of coal burning and stove improvement on risk of pneumonia is not clear. METHODS: We conducted a retrospective cohort study among all farmers born 1917 through 1951 and living in Xuanwei as of 1 January 1976. The analysis included a total of 42,422 cohort members. Follow-up identified all deaths in the cohort from 1976 through 1996. Ages at entry into and at exit from follow-up ranged from 24 to 59 years and from 25 to 80 years, respectively. The record search detected 225 deaths from pneumonia, and 32,332 (76%) were alive as of 31 December 1996. We constructed multivariable Cox models (time variable = age) to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: Use of coal, especially smokeless coal, was positively associated with pneumonia mortality. Annual tonnage and lifetime duration of smoky and smokeless coal use were positively associated with pneumonia mortality. Stove improvement was associated with a 50% reduction in pneumonia deaths (smoky coal users: HR, 0.521; 95% CI, 0.340-0.798; smokeless coal users: HR, 0.449; 95% CI, 0.215-0.937). CONCLUSIONS: Our analysis is the first to suggest that indoor air pollution from unvented coal burning is an important risk factor for pneumonia death in adults and that improving ventilation by installing a chimney is an effective measure to decrease it.

Background & Aims: Increasing evidence points towards a role of hepatitis C virus (HCV) infection in causing malignant lymphomas. We pooled case-control study data to provide robust estimates of the risk of non-Hodgkin's lymphoma (NHL) subtypes after HCV infection. Methods: The analysis included 7 member studies from the International Lymphoma Epidemiology Consortium (InterLymph) based in Europe, North America, and Australia. Adult cases of NHL (n = 4784) were diagnosed between 1988 and 2004 and controls (n = 6269) were matched by age, sex, and study center. All studies used third-generation enzyme-linked immunosorbent assays to test for antibodies against HCV in serum samples. Participants who were human immunodeficiency virus positive or were organ-transplant recipients were excluded. Results: HCV infection was detected in 172 NHL cases (3.60%) and in 169 (2.70%) controls (odds ratio [OR], 1.78; 95% confidence interval [CI], 1.40-2.25). In subtype-specific analyses, HCV prevalence was associated with marginal zone lymphoma (OR, 2.47; 95% CI, 1.44-4.23), diffuse large B-cell lymphoma (OR, 2.24; 95% CI, 1.68-2.99), and lymphoplasmacytic lymphoma (OR, 2.57; 95% CI, 1.14-5.79). Notably, risk estimates were not increased for follicular lymphoma (OR, 1.02; 95% CI, 0.65-1.60). Conclusions: These results confirm the association between HCV infection and NHL and specific B-NHL subtypes (diffuse large B-cell lymphoma, marginal zone lymphoma, and lymphoplasmacytic lymphoma). © 2008 AGA Institute.