Association of Streptococcus gallolyticus subspecies gallolyticus with colorectal cancer: Serological evidence

The colonic opportunist Streptococcus gallolyticus subspecies gallolyticus (SGG) is potentially associated with colorectal cancer (CRC). Large‐scale seroepidemiological data for SGG antibodies and their possible association with CRC is currently missing. Associations between CRC and antibody responses to SGG were examined in 576 CRC cases and 576 controls matched by sex, age and province from a population‐based multicase–control project (MCC‐Spain). MCC‐Spain was conducted between 2008 and 2013 in 12 Spanish provinces. Antibody responses to recombinant affinity‐purified SGG pilus proteins Gallo1569, 2039, 2178 and 2179 were analysed by multiplex serology. Polyomavirus (PyV) JC VP1 and PyV 6 VP1 proteins served as disease‐specificity controls. In the control population, antibody responses to pilus proteins were mostly weak. Antibody responses to individual pilus proteins Gallo2039 (OR: 1.58, 95% CI: 1.09–2.28), Gallo2178 (OR: 1.58, 95% CI: 1.09–2.30) and Gallo2179 (OR: 1.45, 95% CI: 1.00–2.11) were significantly associated with CRC risk. The association was stronger for positivity to two or more pilus proteins of Gallo1569, Gallo2178 and Gallo2179 (OR:1.93, 95% CI: 1.04–3.56) and for double‐positivity to Gallo2178 and Gallo2179 (OR: 3.54, 95% CI: 1.49–8.44). The association between SGG infection and CRC risk was stronger among individuals younger than 65 years. For the first time we demonstrated a statistically significant association of exposure to SGG antigens and CRC in a large seroepidemiological study. These results should stimulate further studies on the role of SGG in CRC pathogenesis.     

Serology of Streptococcus gallolyticus subspecies gallolyticus and its association with colorectal cancer and precursors

Streptococcus gallolyticus subspecies gallolyticus (SGG) is potentially associated with colorectal cancer (CRC) and its precursors. A previous case‐control study measured antibody responses to SGG pilus proteins Gallo2178 and Gallo2179 and identified significant associations with a small fraction of CRC cases. We aimed at replicating and expanding these findings in an independent study including additional SGG antigens and explored the association with precancerous lesions. We applied multiplex serology to measure antibodies to eleven SGG proteins in serum samples of a screening colonoscopy trial (BliTz study) including participants diagnosed with either non‐advanced adenoma (NAA, n = 30), advanced adenoma (AA, n = 100), CRC (n = 50) or controls (n = 228). In addition, we analyzed CRC samples (n = 318) from patients recruited in a clinical setting (DACHSplus study). The association of antibody responses to SGG pilus proteins Gallo2178 and Gallo2179 with CRC was replicated with 4% positive DACHSplus cases compared to 0% positive BliTz controls. Positivity to two or more proteins of a newly defined panel of six SGG markers was significantly associated with CRC in the DACHSplus study (OR: 1.81, 95% CI: 1.07–3.06). Odds for CRC, AA and NAA in the BliTz study were also increased with antibody responses to SGG, and the association was significant for NAA (OR: 2.98, 95% CI: 1.18–7.57). Antibody responses to SGG are associated with CRC and its precursors. The newly identified SGG six‐marker panel and associations found with precancerous lesions should be further explored.     

A CagA‐independent cluster of antigens related to the risk of noncardia gastric cancer: Associations between Helicobacter pylori antibodies and gastric adenocarcinoma explored by multiplex serology

Because of the differences in bacterial epitopes and host characteristics, infections with Helicobacter pylori (H. pylori) induce different immune responses. We explored the possibility that certain antibody response patterns are more closely linked to gastric adenocarcinoma (GAC) than others. In a Swedish population‐based case‐control study, serum samples were obtained from 268 cases and 222 controls, aged 40–79 years and frequency‐matched according to age and sex. We measured antibodies against 17 H. pylori proteins using multiplex serology. Associations were estimated with multivariably adjusted logistic regression models, using odds ratio (OR) with 95% confidence interval (CI) as measures of relative risk. Associations were essentially confined to non‐cardia GAC but did not differ significantly between intestinal and diffuse subtypes. Point estimates for all antibodies were above unity, 15 significant with top three being CagA (OR = 9.2), GroEL (6.6), HyuA (3.6). ORs were substantially attenuated in individuals with chronic atrophic gastritis. Principal component analysis identified two significant factors: a CagA‐dominant factor (antibodies against CagA, VacA and Omp as prominent markers), and a non‐CagA factor (antibodies against NapA and Catalase as prominent markers). Both factors showed dose‐dependent associations with non‐cardia GAC risk (CagA‐dominant factor, highest vs. lowest quartiles, OR = 16.2 [95% CI 4.8–54.9]; non‐CagA factor OR = 5.3 [95% CI 2.1–13.3]). Overall, our results confirm that serum antibodies against different H. pylori proteins are associated with the presence of non‐cardia GAC. Although strongest association is detected by antibodies against CagA and covarying proteins, a pattern of antibodies unrelated to CagA is also significantly linked to the risk of non‐cardia GAC.     

Infection,antibiotic therapy and risk of colorectal cancer: A nationwide nested case–control study in patients with Type 2 diabetes mellitus

Patients with Type 2 diabetes mellitus are at a higher risk of colorectal cancer (CRC). The objective of our study was to examine the inter‐relationship among infection sites, systemic antibiotic use and risk of CRC among patients with Type 2 diabetes mellitus. From a diabetic cohort from the Taiwan's National Health Insurance claims database, we identified 3,593 incident colon cancer cases, 1,979 rectal cancer cases and 22,288 controls and conducted a nested case–control study to examine the association between antibiotic use and CRC incidence. Logistic regression models were applied to estimate the odds ratio (OR) and the 95% confidence interval (95% CI) between infection sites, antibiotic use and CRC incidence. Patients with intra‐abdominal infection were significantly associated with increased risk for colon cancer (OR = 2.01, 95% CI = 1.73–2.35) and rectal cancer (OR = 1.59, 95% CI = 1.26–2.00). Any antianaerobic antibiotic use was associated with a higher risk of colon cancer (OR = 2.31, 95% CI = 2.12–2.52) and rectal cancer (OR = 1.69, 95% CI = 1.50–1.90) but without an obvious dose–response relationship for cumulative use. Antianaerobic antibiotics also increased the risks for those with nonintra‐abdominal infection. No association was found between antiaerobic agent use and the CRC risk. The results suggest intra‐abdominal infections and antianaerobic antibiotic use may be a marker for precancerous lesions or early CRC, although the possibility of antianaerobic antibiotics playing an additional role cannot be excluded. Further research examining the relationship between intra‐abdominal infection, antianaerobic antibiotics use and possible change of microbiota leading to colorectal carcinogenesis is warranted.     

Meta-analysis of 16 studies of the association of alcohol with colorectal cancer

Alcohol consumption is an established risk factor for colorectal cancer (CRC). However, while studies have consistently reported elevated risk of CRC among heavy drinkers, associations at moderate levels of alcohol consumption are less clear. We conducted a combined analysis of 16 studies of CRC to examine the shape of the alcohol–CRC association, investigate potential effect modifiers of the association, and examine differential effects of alcohol consumption by cancer anatomic site and stage. We collected information on alcohol consumption for 14,276 CRC cases and 15,802 controls from 5 case-control and 11 nested case-control studies of CRC. We compared adjusted logistic regression models with linear and restricted cubic splines to select a model that best fit the association between alcohol consumption and CRC. Study-specific results were pooled using fixed-effects meta-analysis. Compared to non-/occasional drinking (≤1 g/day), light/moderate drinking (up to 2 drinks/day) was associated with a decreased risk of CRC (odds ratio [OR]: 0.92, 95% confidence interval [CI]: 0.88–0.98, p = 0.005), heavy drinking (2–3 drinks/day) was not significantly associated with CRC risk (OR: 1.11, 95% CI: 0.99–1.24, p = 0.08) and very heavy drinking (more than 3 drinks/day) was associated with a significant increased risk (OR: 1.25, 95% CI: 1.11–1.40, p < 0.001). We observed no evidence of interactions with lifestyle risk factors or of differences by cancer site or stage. These results provide further evidence that there is a J-shaped association between alcohol consumption and CRC risk. This overall pattern was not significantly modified by other CRC risk factors and there was no effect heterogeneity by tumor site or stage.     

Consumption of meat,traditional and modern processed meat and colorectal cancer risk among the Moroccan population: A large-scale case–control study

The current study aimed to investigate the relationship between red and white meat subtypes, processed meat (divided into traditional “Khlii, Kaddid” and industrially processed meat) and colorectal cancer (CRC) risk, considering CRC subsites, in Moroccan adults. A case–control study was conducted including 2,906 matched case–control pairs recruited from the five largest university hospitals in Morocco. Dietary data were collected through a validated Food Frequency Questionnaire (FFQ). Multivariable odds ratios (OR) and 95% confidence intervals (CI), for the association of CRC risk with meat consumption (high vs. low intake), were estimated using conditional logistic regression models, adjusted for relevant confounding variables. Overall, consumption of red meat was positively associated with colon cancer and CRC risk (OR = 1.23, 95% CI = 1.05–1.44; OR = 1.14, 95% CI = 1.02–1.27), respectively. In contrast, no significant association was observed between the consumption of red meat and rectal cancer risk (OR = 1.05, 95% = 0.90–1.23). Interestingly, while processed meat from industrial processes was positively associated with colon cancer, rectal cancer and CRC (OR = 1.61, 95% CI = 1.27–2.04; OR = 1.73, 95% CI = 1.34–2.23; OR = 1.67, 95% CI = 1.41–1.98), processed meat prepared using traditional methods was inversely associated with colon cancer and CRC risk (OR = 0.74, 95% CI = 0.57–0.98; OR = 0.77, 95% CI = 0.64–0.93), respectively. Furthermore, positive associations were observed between poultry intake and colon cancer risk among men (OR = 1.27, 95% CI = 1.01–1.59). Our study showed similar associations between the consumption of red meat and CRC risk in Morocco as in developed countries, while inverse associations were found for traditionally processed meat products. This is the first study to investigate the differential effects of traditional vs. westernized processed meat products in a developing country. Other studies are needed to confirm these findings and to understand the physiological pathways underlying these associations.     

Association between adult weight gain and colorectal cancer: A dose–response meta‐analysis of observational studies

This study investigated the association between adult weight gain and risk of colorectal cancer (CRC). Using terms related to weight gain and CRC, we searched PubMed, Embase and Web of Science for relevant studies published before June 2014. Two evaluators independently selected studies according to the selection criteria, and eight studies were included (three case–control and five cohort studies). Summary estimates were obtained using fixed‐ or random‐effects models. The relative risk (RR) of the association between adult weight gain and CRC was 1.25 (95% confidence interval [CI], 1.10–1.43); the RR was 1.30 (95% CI, 1.14–1.49) for colon cancer (CC) and 1.27 (95% CI, 1.02–1.58) for rectal cancer (RC) for the highest versus lowest category. For every 5‐kg increase in adult weight, the risk increased by 5% (RR, 1.05; 95% CI, 1.02–1.09) for CRC, 6% (RR, 1.06; 95% CI, 1.02–1.11) for CC and 6% (RR, 1.06; 95% CI, 1.03–1.08) for RC. The subgroup analyses showed a positive association between adult weight gain and risk of CRC only in men, and the RR was 1.65 (95% CI, 1.42–1.92) for the highest versus lowest category of adult weight gain and 1.10 (95% CI, 1.06–1.15) for a 5‐kg increase in adult weight. In conclusion, there is evidence that adult weight gain is associated with an increased risk of CRC. However, the positive association between adult weight gain and risk of CRC is stronger among men than among women.     

A prospective analysis of telomere length and pancreatic cancer in the alpha‐tocopherol beta‐carotene cancer (ATBC) prevention study

Smoking and diabetes, consistent risk factors for pancreatic cancer, are also factors that influence telomere length maintenance. To test whether telomere length is associated with pancreatic cancer risk, we conducted a nested case–control study in the Alpha‐Tocopherol, Beta‐Carotene Cancer Prevention (ATBC) Study cohort of male smokers, aged 50–69 years at baseline. Between 1992 and 2004, 193 incident cases of pancreatic adenocarcinoma occurred (mean follow‐up from blood draw: 6.3 years) among participants with whole blood samples available for telomere length assays. For these cases and 660 controls, we calculated odds ratios (OR) and 95% confidence intervals using unconditional logistic regression, adjusting for age, number of years smoked regularly, and history of diabetes mellitus. Telomere length was categorized into quartiles (shortest to longest) and analyzed as both a categorical and a continuous normal variable (reported per 0.2 unit increase in telomere length). All statistical tests were two‐sided. Longer telomere length was significantly associated with increased pancreatic cancer risk (continuous OR = 1.26 95% CI = 1.09–1.46; highest quartile compared to lowest, OR = 1.57, 95% CI = 1.01–2.43, p‐trend = 0.007). This association remained for subjects diagnosed within the first five years of blood draw (continuous OR = 1.46, 95% CI = 1.19–1.79 highest quartile OR = 2.92, 95% CI = 1.47–5.77, p‐trend = 0.002), but not those diagnosed greater than five years after blood draw (continuous OR = 1.03, 95% CI = 0.85–1.22; highest quartile OR = 1.04, 95% CI = 0.60–1.79). This is the first prospective study to suggest an association between longer blood leukocyte telomere length and increased pancreatic cancer risk.     

Family history and the risk of colorectal cancer: The importance of patients' history of colonoscopy

Registry‐based studies on the risk of colorectal cancer (CRC) for persons with a family history (FH) typically did not control for important covariates, such as history of colonoscopy. We aimed to quantify the association between FH and CRC risk, carefully accounting for potential confounders. We conducted a population‐based case–control study in Germany. A total of 4,313 patients with a first diagnosis of CRC (cases) and 3,153 controls recruited from 2003 to 2014 were included. We used multiple logistic regression analyses to assess the association between FH and risk of CRC with odds ratios (OR) and the resulting 95% confidence intervals (95% CI). A total of 582 cases (13.5%) and 321 (10.2%) controls reported a history of CRC in a first‐degree relative, which was associated with a 41% increase in risk of CRC (OR: 1.41, 95% CI 1.22–1.63) after adjustment for sex and age. The OR substantially increased to 1.73 (95% CI, 1.48–2.03) after comprehensive adjustment including previous colonoscopies. Irrespective of their FH status, persons with history of colonoscopies had a lower CRC risk compared with persons without previous colonoscopies and without family history (OR: 0.25, 95% CI, 0.22–0.28 for persons without FH and OR 0.45, 95% CI, 0.36–0.56 for persons with FH). In an era of widespread use of colonoscopy, adjusting for previous colonoscopy is therefore crucial for deriving valid estimates of FH‐related CRC risk. Colonoscopy reduces the risk of CRC among those with FH far below levels of people with no FH and no colonoscopy.     

Association between time to colonoscopy after a positive guaiac fecal test result and risk of colorectal cancer and advanced stage disease at diagnosis

We evaluated time to colonoscopy after a positive guaiac-based fecal occult blood test (gFOBT) result and its association with the risk of overall colorectal cancer (CRC) and advanced-stage disease at diagnosis. We conducted a retrospective cohort study (2011–2013) within the Clalit Health Services, Israel. Participants were patients between 50 and 74 years old with a positive gFOBT result who had follow-up colonoscopies within 24 months. The exposure was time to colonoscopy, and the main outcome measure was a risk for overall and advanced CRC (defined as Stages III–IV). Odds ratios (ORs) and 95% confidence intervals (CIs) were adjusted for patient demographics and baseline risk factors. Of the 17,958 patients with positive gFOBT results (median age, 61 years [interquartile range, 56–67 years]; women, 52.2%), there were 685 cases of CRC and 156 cases of an advanced-stage disease diagnosed. The rate of cancer diagnosis at 0–3, 4–6, 7–9, 10–12 and 13–24 months was 3.9%, 2.5%, 3.5%, 4.2% and 7.3%, respectively (p < 0.001). Compared to colonoscopy follow-up within 0–3 months, risks for any CRC and advanced stage disease were higher for a follow-up of 12–24 months: OR, 1.97 (95% CI, 1.51–2.56) and 1.88 (95% CI, 1.43–2.46), respectively. For right-sided cancer (n = 194), an increased risk starts at 10 months, OR, 1.91 (95% CI 1.03–3.56). A result of 3–6 positive fields was significantly associated diagnosis of cancer (OR, 5.52; 95% CI, 4.71–6.46) and advanced stage disease (OR, 8.07; 95% CI, 5.74–11.36). Encouraging an early uptake of colonoscopy and targeting those with 10–24 months delay and a 3–6 positive fields is warranted.     

Serologic markers of viral infection and risk of non‐Hodgkin lymphoma: A pooled study of three prospective cohorts in China and Singapore

Incidence rates of non‐Hodgkin lymphoma (NHL) and distributions of certain viruses differ between East Asian and Western populations. There are limited data on associations between serologic markers of multiple viral infections in pre‐diagnostic blood and NHL risk in East Asians. We conducted a nested case‐control study of 214 NHL cases and 214 matched controls from three population‐based prospective cohorts in Shanghai and Singapore. Antibodies against antigens from herpesviruses, Hepatitis B (HBV) and C (HCV) virus and polyomaviruses were measured in plasma or serum using fluorescent bead‐based multiplex assays. Conditional logistic regression was used to evaluate associations between antibody levels and NHL risk. An increased risk of NHL was observed for higher compared to lower EA‐D (Odds Ratio (OR) = 2.04, 95% Confidence Interval (CI) = 1.10‐3.81; p_trend = 0.005) and ZEBRA (OR = 2.17, 95% CI = 0.96‐4.89; p_trend = 0.008) Epstein‐Barr Virus (EBV) antibodies, as well as for antibody seropositivity against the IE1A human herpesvirus‐6 (HHV‐6) antigen (OR = 1.85, 95% CI = 1.04‐3.29). An increased NHL risk was also observed for higher compared to lower antibodies against the HBV‐HBc and HBe antigens. An increased risk of NHL in relation to EBV and HBV infection in East Asians is consistent with findings in several studies of Western populations, suggesting similar viral risk factors for NHL in these diverse populations with distinct patterns of NHL. The association between HHV‐6 antibodies and NHL has not previously been reported in a prospective study in this population and will require replication.     

Circulating 25‐hydroxyvitamin D,vitamin D‐binding protein and risk of prostate cancer

We recently reported a significant positive association between 25‐hydroxyvitamin D [25(OH)D], the accepted biomarker of vitamin D status, and prostate cancer risk. To further elucidate this association, we examined the influence of vitamin D‐binding protein (DBP), the primary transporter of vitamin D compounds in the circulation. Prediagnostic serum concentrations of DBP were assayed for 950 cases and 964 matched controls with existing 25(OH)D measurements within the Alpha‐Tocopherol, Beta‐Carotene Cancer Prevention Study of Finnish men. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs), and statistical tests were two sided. Serum DBP modified the association between serum 25(OH)D and prostate cancer, with higher risk for elevated 25(OH)D levels observed primarily among men having DBP concentrations above the median (OR = 1.81, 95% CI: 1.18–2.79 for highest vs. lowest quintile, p‐trend = 0.001) compared to those with DBP below the median (OR = 1.22, 95% CI: 0.81–1.84, p‐trend 0.97; p‐interaction = 0.04). Serum DBP was not associated with prostate cancer risk overall (OR = 0.96, 95% CI: 0.70–1.33 for highest vs. lowest quintile); however, high serum DBP was associated with significantly decreased risk of prostate cancer in men with lower (<median) 25(OH)D concentrations (OR = 0.59, 95% CI: 0.38–0.90 for highest vs. lowest quintile, p‐trend = 0.003) and increased risk in men with higher 25(OH)D concentrations (OR = 1.47, 95% CI: 0.98–2.20, p‐trend 0.10, p‐interaction = 0.02). Our data suggest that the primary vitamin D carrier protein, DBP, modulates the impact of vitamin D status on prostate cancer.     

The U-shaped association between body mass index and gastric cancer risk in the Helicobacter pylori Biomarker Cohort Consortium: A nested case–control study from eight East Asian cohort studies

The association between body mass index (BMI) and noncardia gastric cancer (NCGC) risk remains controversial. The purpose of our study was to examine the association of BMI with NCGC risk with consideration of Helicobacter pylori (HP) biomarkers. This international nested case–control study, composed of 1,591 incident NCGC cases and 1,953 matched controls, was established from eight cohorts in China, Japan and Korea, where the majority of NCGCs are diagnosed worldwide. HP antibody biomarkers were measured in blood collected at cohort enrollment by multiplex serology. The NCGC risk according to baseline BMI was estimated using logistic regression to produce odds ratios (ORs) and 95% confidence intervals (CIs). We found a U-shaped association between BMI category and NCGC risk. Compared to those with reference BMI (22.6–25.0 kg/m²), those with lower and higher BMI had an increased NCGC risk (BMI <18.5 kg/m², OR = 1.56, 95% CI = 1.04–2.34; BMI >27.5 kg/m², OR = 1.48, 95% CI = 1.15–1.91; adjusted for age, sex and smoking). The U-shaped association was persistent among subjects with HP infection and high-risk biomarkers (HP+ CagA+: BMI <18.5 kg/m², OR = 1.60, 95% CI = 1.00–2.55; BMI >27.5 kg/m², OR = 1.59, 95% CI = 1.21–2.11; and Omp+ HP0305+: BMI <18.5 kg/m², OR = 1.88, 95% CI = 1.04–3.42; BMI >27.5 kg/m², OR = 1.70, 95% CI = 1.20–2.42, respectively). Our study provides evidence of significantly increased NCGC risk among individuals with low or high BMI, including in subjects with high-risk HP biomarkers (HP+ CagA+, Omp+ HP0305+) in the high-risk area of East Asia.     

Circulating sex hormone levels and colorectal cancer risk in Japanese postmenopausal women: The JPHC nested case–control study

Previous epidemiological studies evaluated endogenous sex hormone levels and colorectal cancer (CRC) risk have yielded inconsistent results. Also, it is unknown if consumption of dietary isoflavones may influence the endogenous sex hormones and CRC relationships. We conducted a nested case–control study within the JPHC Study Cohort II wherein 11,644 women provided blood samples at the 5-year follow-up survey. We selected two matched controls for each case from the cohort (185 CRC cases and 361 controls). Multivariable conditional logistic regression was used to estimate odds ratios (ORs), 95% confidence intervals (CIs) for the association between circulating sex hormone levels and CRC risk. Comparing extreme tertiles, circulating testosterone levels were positively associated with CRC risk (OR = 2.10, 95% CI = 1.11–3.99, p for trend = 0.03). Levels of estradiol, SHBG, and progesterone were not associated with CRC risk. In a subgroup analysis by dietary isoflavone intake, SHBG levels were positively associated with CRC risk among those with low total isoflavone intake (p for trend = 0.03), with a statistically nonsignificant inverse association among those with high total isoflavone intake (p for trend = 0.22; p for interaction = 0.002). Endogenous levels of testosterone were positively associated with CRC among postmenopausal women. The association of endogenous SHBG with CRC development may be altered by the level of dietary isoflavone intake.     

Mendelian randomisation implicates hyperlipidaemia as a risk factor for colorectal cancer

While elevated blood cholesterol has been associated with an increased risk of colorectal cancer (CRC) in observational studies, causality is uncertain. Here we apply a Mendelian randomisation (MR) analysis to examine the potential causal relationship between lipid traits and CRC risk. We used single nucleotide polymorphisms (SNPs) associated with blood levels of total cholesterol (TC), triglyceride (TG), low‐density lipoprotein (LDL), and high‐density lipoprotein (HDL) as instrumental variables (IV). We calculated MR estimates for each risk factor with CRC using SNP‐CRC associations from 9,254 cases and 18,386 controls. Genetically predicted higher TC was associated with an elevated risk of CRC (odds ratios (OR) per unit SD increase = 1.46, 95% confidence interval [CI]: 1.20–1.79, p = 1.68 × 10⁻⁴). The pooled ORs for LDL, HDL, and TG were 1.05 (95% CI: 0.92–1.18, p = 0.49), 0.94 (95% CI: 0.84–1.05, p = 0.27), and 0.98 (95% CI: 0.85–1.12, p = 0.75) respectively. A genetic risk score for 3‐hydoxy‐3‐methylglutaryl‐coenzyme A reductase (HMGCR ) to mimic the effects of statin therapy was associated with a reduced CRC risk (OR = 0.69, 95% CI: 0.49–0.99, p = 0.046). This study supports a causal relationship between higher levels of TC with CRC risk, and a further rationale for implementing public health strategies to reduce the prevalence of hyperlipidaemia.     

A prospective investigation of serum 25‐hydroxyvitamin D and risk of lymphoid cancers

Studies indicate that higher sun exposure, especially in the recent past, is associated with reduced risk of non‐Hodgkin lymphoma (NHL). Ultraviolet radiation‐derived vitamin D may be protective against lymphomagenesis. We examined the relationship between prediagnostic serum 25‐hydroxyvitamin D (25(OH)D) and lymphoid cancer risk in a case–control study nested within the Alpha‐Tocopherol Beta‐Carotene Cancer Prevention Study cohort (1985–2002) of 29,133 Finnish male smokers (ages 50–69). We identified 270 incident lymphoid cancer cases and matched them individually with 538 controls by birth‐year and month of fasting blood draw at baseline. In conditional logistic regression models for 10 nmol/L increments or tertile comparisons, serum 25(OH)D was not associated with the risk of overall lymphoid cancers, NHL (n = 208) or multiple myeloma (n = 41). Odds ratios (OR) for NHL for higher tertiles were 0.75 (95% confidence interval (CI), 0.50, 1.14) and 0.82 (95% CI, 0.53, 1.26). The 25(OH)D‐NHL association, however, differed by follow‐up duration at diagnosis. Cases diagnosed less than 7 years from the baseline showed an inverse association (OR for highest vs. lowest tertile = 0.43; 95% CI: 0.23, 0.83; p for trend = 0.01), but not later diagnoses (OR = 1.52; 95% CI: 0.82, 2.80; p for trend = 0.17). The inverse association found for close exposure to diagnosis was not confounded by other risk factors for lymphoma or correlates of 25(OH)D. Although our findings suggest that circulating 25(OH)D is not likely associated with overall lymphoid cancer, they indicate a potentially protective effect on short‐term risk of NHL. © 2008 Wiley‐Liss, Inc.     

HIV and human herpesvirus 8 co‐infection across the globe: Systematic review and meta‐analysis

HIV‐infection is an important risk factor for developing Kaposi sarcoma (KS), but it is unclear whether HIV‐positive persons are also at increased risk of co‐infection with human herpesvirus 8 (HHV‐8), the infectious cause of KS. We systematically searched literature up to December 2012 and included studies reporting HHV‐8 seroprevalence for HIV‐positive and HIV‐negative persons. We used random‐effects meta‐analysis to combine odds ratios (ORs) of the association between HIV and HHV‐8 seropositivity and conducted random‐effects meta‐regression to identify sources of heterogeneity. We included 93 studies with 58,357 participants from 32 countries in sub‐Saharan Africa, North and South America, Europe, Asia, and Australia. Overall, HIV‐positive persons were more likely to be HHV‐8 seropositive than HIV‐negative persons (OR 1.99, 95% confidence interval [CI] 1.70–2.34) with considerable heterogeneity among studies (I² 84%). The association was strongest in men who have sex with men (MSM, OR 3.95, 95% CI 2.92–5.35), patients with hemophilia (OR 3.11, 95% CI 1.19–8.11), and children (OR 2.45, 95% CI 1.58–3.81), but weaker in heterosexuals who engage in low‐risk (OR 1.42, 95% CI 1.16–1.74) or high‐risk sexual behavior (OR 1.66, 95% CI 1.27–2.17), persons who inject drugs (OR 1.66, 95% CI 1.28–2.14), and pregnant women (OR 1.68, 95% CI 1.15–2.47), p value for interaction <0.001. In conclusion, HIV‐infection was associated with an increased HHV‐8 seroprevalence in all population groups examined. A better understanding of HHV‐8 transmission in different age and behavioral groups is needed to develop strategies to prevent HHV‐8 transmission.     

Association of HLA‐DRB1, interleukin‐6 and cyclin D1 polymorphisms with cervical cancer in the Swedish population—A candidate gene approach

High‐risk human papillomavirus (hrHPV) infection is the major risk factor for cervical cancer (CxCa). The role of genetic susceptibility in the disease has been suggested, but the existing data lack consistency. We conducted a nested case‐control study on 973 CxCa cases and 1,763 matched controls, from two Swedish population‐based cohorts to examine the association of common genetic variants with CxCa risk. Human leukocyte antigen (HLA) alleles and 24 other polymorphisms in 14 genes were selected on the basis of reported association or mechanistic plausibility with an HPV infection or cervical cancer development. Genotyping was conducted using multiplex PCR and Luminex technology. A significant association of CxCa with various polymorphisms was observed: rs1800797 in the IL‐6 gene (odds ratio [OR] = 0.88, 95% confidence intervals [CI]: 0.79–0.99); rs1041981 in the LTA gene (OR = 0.87, 95% CI: 0.78–0.98), and rs9344 in the CCND1 gene (OR = 1.14, 95% CI: 1.02–1.27), for those individuals carrying the rare allele. Additionally, the alleles 0401 and 1501 of the HLA class II DRB1 locus were associated with an increased risk (OR = 1.23, 95% CI: 1.04–1.45 and OR = 1.29, 95% CI: 1.11–1.50, respectively), and allele 1301 was associated with decreased risk (OR = 0.59, 95% CI: 0.47–0.73). The effects of CCND1 and the HLA*DRB1 alleles were independent of the effect of smoking. We did not find any association of risk with polymorphisms in genes related to the innate immune system. In conclusion, our study provides evidence for genetic susceptibility to CxCa due to variations in genes involved in the immune system and in cell cycle. © 2009 UICC     

Genome‐wide association study and meta‐analysis in Northern European populations replicate multiple colorectal cancer risk loci

Genome‐wide association studies have been successful in elucidating the genetic basis of colorectal cancer (CRC), but there remains unexplained variability in genetic risk. To identify new risk variants and to confirm reported associations, we conducted a genome‐wide association study in 1,701 CRC cases and 14,082 cancer‐free controls from the Finnish population. A total of 9,068,015 genetic variants were imputed and tested, and 30 promising variants were studied in additional 11,647 cases and 12,356 controls of European ancestry. The previously reported association between the single‐nucleotide polymorphism (SNP) rs992157 (2q35) and CRC was independently replicated (p = 2.08 × 10⁻⁴; OR, 1.14; 95% CI, 1.06–1.23), and it was genome‐wide significant in combined analysis (p = 1.50 × 10⁻⁹; OR, 1.12; 95% CI, 1.08–1.16). Variants at 2q35, 6p21.2, 8q23.3, 8q24.21, 10q22.3, 10q24.2, 11q13.4, 11q23.1, 14q22.2, 15q13.3, 18q21.1, 20p12.3 and 20q13.33 were associated with CRC in the Finnish population (false discovery rate < 0.1), but new risk loci were not found. These results replicate the effects of multiple loci on the risk of CRC and identify shared risk alleles between the Finnish population isolate and outbred populations.     

Fruit and vegetable consumption,Helicobacter pylori antibodies,and gastric cancer risk: A pooled analysis of prospective studies in China,Japan, and Korea

Epidemiological findings on the association between fruit and vegetable consumption and gastric cancer risk remain inconsistent. The present analysis included 810 prospectively ascertained non‐cardia gastric cancer cases and 1,160 matched controls from the Helicobacter pylori Biomarker Cohort Consortium, which collected blood samples, demographic, lifestyle, and dietary data at baseline. Conditional logistic regression adjusting for total energy intake, smoking, and H. pylori status, was applied to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for gastric cancer risk across cohort‐ and sex‐specific quartiles of fruit and vegetable intake. Increasing fruit intake was associated with decreasing risk of non‐cardia gastric cancer (OR = 0.71, 95% CI: 0.52–0.95, p trend = 0.02). Compared to low‐fruit consumers infected with CagA‐positive H. pylori, high‐fruit consumers without evidence of H. pylori antibodies had the lowest odds for gastric cancer incidence (OR = 0.12, 95% CI: 0.06–0.25), whereby the inverse association with high‐fruit consumption was attenuated among individuals infected with CagA‐positive H. pylori (OR = 0.82, 95% CI: 0.66–1.03). To note, the small number of H. pylori negative individuals does influence this finding. We observed a weaker, nondose‐response suggestion of an inverse association of vegetable intake with non‐cardia gastric cancer risk. High fruit intake may play a role in decreasing risk of non‐cardia gastric cancer in Asia.