A genome-wide association study of prostate cancer in West African men.

Age-adjusted mortality rates for prostate cancer are higher for African-American men compared with those of European ancestry. Recent data suggest that West African men also have elevated risk for prostate cancer relative to European men. Genetic susceptibility to prostate cancer could account for part of this difference. We conducted a genome-wide association study (GWAS) of prostate cancer in West African men in the Ghana Prostate Study. Association testing was performed using multivariable logistic regression adjusted for age and genetic ancestry for 474 prostate cancer cases and 458 population-based controls on the Illumina HumanOmni-5 Quad BeadChip. The most promising association was at 10p14 within an intron of a long non-coding RNA (lncRNA RP11-543F8.2) 360 kb centromeric of GATA3 (p = 1.29E-7). In sub-analyses, SNPs at 5q31.3 were associated with high Gleason score (≥7) cancers, the strongest of which was a missense SNP in PCDHA1 (rs34575154, p = 3.66E-8), and SNPs at Xq28 (rs985081, p = 8.66E-9) and 6q21 (rs2185710, p = 5.95E-8) were associated with low Gleason score (<7) cancers. We sought to validate our findings in silico in the African Ancestry Prostate Cancer GWAS Consortium, but only one SNP, at 10p14, replicated at p < 0.05. Of the 90 prostate cancer loci reported from studies of men of European, Asian or African-American ancestry, we were able to test 81 in the Ghana Prostate Study, and 10 of these replicated at p < 0.05. Further genetic studies of prostate cancer in West African men are needed to confirm our promising susceptibility loci.

Sex-specific associations between body mass index, waist circumference and the risk of Barrett's oesophagus: a pooled analysis from the international BEACON consortium.

OBJECTIVE: Barrett's oesophagus is a precursor lesion of oesophageal adenocarcinoma, a cancer that, in the USA, has increased in incidence over 600% during the past 40 years. Barrett's oesophagus and oesophageal adenocarcinoma are much more common among men than among women; this finding is unexplained and most earlier studies lacked sufficient numbers of women to evaluate sex-specific risk factors. We leveraged the power of an international consortium to assess sex-specific relationships between body mass index (BMI), abdominal circumference and Barrett's oesophagus. DESIGN: Four case-control studies provided a total of 1102 cases (316 women, 786 men) and 1400 population controls (436 women, 964 men) for analysis. Study-specific estimates, generated using individual participant data, were combined using random effects meta-analysis. RESULTS: Waist circumference was significantly associated with Barrett's oesophagus, even after adjustment for BMI; persons in the highest versus the lowest quartiles of waist circumference had approximately 125% and 275% increases in the odds of Barrett's oesophagus among men and women, respectively (OR 2.24, 95% CI 1.08 to 4.65, I(2)=57; OR 3.75, 95% CI 1.47 to 9.56, I(2)=0). In contrast, there was no evidence of a significant association between BMI and the risk of Barrett's oesophagus, with or without adjustment for waist circumference. CONCLUSIONS: Waist circumference, independent of BMI, was found to be a risk factor for Barrett's oesophagus among both men and women. Future studies examining the biological mechanisms of this association will extend our knowledge regarding the pathogenesis of Barrett's oesophagus.

Non-acid reflux: the missing link between gastric atrophy and esophageal squamous cell carcinoma?

Esophageal cancer is the eighth most common incident cancer in the world and, due to the poor survival rate it confers, ranks sixth among all cancers in mortality. In developed countries of the western world, the incidence of esophageal squamous cell carcinoma (ESCC) has undergone a decline and adenocarcinoma now constitutes approximately half of all esophageal cancers. In these relatively low-risk areas, tobacco smoking and alcohol consumption account for ~90% of ESCC cases. Eastern countries have much higher incidences of ESCC and epidemiologic evidence would suggest that there are additional unknown causal mechanisms. Gastric atrophy has consistently been associated with ESCC, but its causal relevance has been questioned. In this issue of the American Journal of Gastroenterology, Uno et al. offer evidence that a causal link between these two entities is non-acid reflux.

Family cancer history affecting risk of colorectal cancer in a prospective cohort of Chinese women.

An elevated risk of colorectal cancer has been associated with sporadic colorectal cancer in first-degree relatives, mostly in Western populations. Limited data exist from traditionally low-risk areas, such as Asia, where the prevalence of risk factors may differ. We examined the association of family history of cancer and subsequent colorectal cancer risk in a cohort of traditionally low-risk Chinese women. We followed 73,358 women in the Shanghai Women's Health Study for cancer incidence until December 2005. After an average of 7 years of follow-up, 391 women were diagnosed with colorectal cancer. We calculated hazard ratios and 95% confidence intervals using Cox proportional hazards models adjusted for age, smoking, family income, education, body mass index, physical activity, and history of diabetes. We observed a significant association between colorectal cancer risk and history of a parent being diagnosed with colorectal cancer (hazard ratio: 3.34; 95% confidence interval: 1.58, 7.06). No association was observed for colorectal cancer diagnosed among siblings. Colorectal cancer risk was not influenced by a positive family history of cancer generally or any of the other cancers investigated (lung, breast, prostate, gastric, esophageal, endometrial, ovarian, urinary tract, central nervous system, and small bowel). Our cohort results suggest that consistent with findings from Western populations, having a family history of colorectal cancer may influence colorectal cancer risk to a similar extent in a low-risk population.