Browsing by Author "Guilford P"

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    Germline CDH1 mutations are a significant contributor to the high frequency of early-onset diffuse gastric cancer cases in New Zealand Māori.
    (Springer Nature, 2018-03-27) Hakkaart C; Ellison-Loschmann L; Day R; Sporle A; Koea J; Harawira P; Cheng S; Gray M; Whaanga T; Pearce N; Guilford P
    New Zealand Māori have a considerably higher incidence of gastric cancer compared to non-Māori, and are one of the few populations worldwide with a higher prevalence of diffuse-type disease. Pathogenic germline CDH1 mutations are causative of hereditary diffuse gastric cancer, a cancer predisposition syndrome primarily characterised by an extreme lifetime risk of developing diffuse gastric cancer. Pathogenic CDH1 mutations are well described in Māori families in New Zealand. However, the contribution of these mutations to the high incidence of gastric cancer is unknown. We have used next-generation sequencing, Sanger sequencing, and Multiplex Ligation-dependent Probe Amplification to examine germline CDH1 in an unselected series of 94 Māori gastric cancer patients and 200 healthy matched controls. Overall, 18% of all cases, 34% of cases diagnosed with diffuse-type gastric cancer, and 67% of cases diagnosed aged less than 45 years carried pathogenic CDH1 mutations. After adjusting for the effect of screening known HDGC families, we estimate that 6% of all advanced gastric cancers and 13% of all advanced diffuse-type gastric cancers would carry germline CDH1 mutations. Our results demonstrate that germline CDH1 mutations are a significant contributor to the high frequency of diffuse gastric cancer in New Zealand Māori.
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    Risk of stomach cancer in Aotearoa/New Zealand: A Māori population based case-control study.
    (2017) Ellison-Loschmann L; Sporle A; Corbin M; Cheng S; Harawira P; Gray M; Whaanga T; Guilford P; Koea J; Pearce N
    Māori, the indigenous people of New Zealand, experience disproportionate rates of stomach cancer, compared to non-Māori. The overall aim of the study was to better understand the reasons for the considerable excess of stomach cancer in Māori and to identify priorities for prevention. Māori stomach cancer cases from the New Zealand Cancer Registry between 1 February 2009 and 31 October 2013 and Māori controls, randomly selected from the New Zealand electoral roll were matched by 5-year age bands to cases. Logistic regression was used to estimate odd ratios (OR) and 95% confidence intervals (CI) between exposures and stomach cancer risk. Post-stratification weighting of controls was used to account for differential non-response by deprivation category. The study comprised 165 cases and 480 controls. Nearly half (47.9%) of cases were of the diffuse subtype. There were differences in the distribution of risk factors between cases and controls. Of interest were the strong relationships seen with increased stomach risk and having >2 people sharing a bedroom in childhood (OR 3.30, 95%CI 1.95-5.59), testing for H pylori (OR 12.17, 95%CI 6.15-24.08), being an ex-smoker (OR 2.26, 95%CI 1.44-3.54) and exposure to environmental tobacco smoke in adulthood (OR 3.29, 95%CI 1.94-5.59). Some results were attenuated following post-stratification weighting. This is the first national study of stomach cancer in any indigenous population and the first Māori-only population-based study of stomach cancer undertaken in New Zealand. We emphasize caution in interpreting the findings given the possibility of selection bias. Population-level strategies to reduce the incidence of stomach cancer in Māori include expanding measures to screen and treat those infected with H pylori and a continued policy focus on reducing tobacco consumption and uptake.