Genetic variants in CYP and GST genes, smoking and risk for head and neck cancers: a gene-environment interaction hospital-based case-control study among Canadian Caucasians.

The evidence for genetic polymorphisms in genes encoding cytochrome P450 (CYP) and glutathione S-transferase (GST) enzymes as risk factors for squamous cell carcinomas of the head and neck (SCCHN) in Caucasians is conflicting. Furthermore, the interactive effects with smoking have not been documented. We estimated the effects of five single nucleotide polymorphisms and two copy number variants associated with CYP and GST genes, as well as their interactive effects with smoking, on SCCHN risk among Caucasians from a case-control study conducted in Montreal, Canada. The study involved 389 incident SCCHN cases and 429 controls, frequency-matched by age and sex, recruited from four main hospitals between 2005 and 2013. Life-course-based interviews collected information on tobacco smoking history and other risk behaviors. DNA was isolated from oral exfoliated cells and genotyped for genetic variants. Unconditional logistic regression models estimated odds ratios (OR) and 95% confidence intervals (CI) for main, joint effect, stratum-specific and interaction estimates among non-, moderate and heavy smokers. Carriers of GSTP1 105Val (versus non-carriers) had a lower risk of SCCHN (OR = 0.71, 95% CI: 0.53, 0.95), which was observed for heavy smokers (OR = 0.59, 95% CI: 0.36, 0.95) and non-smokers alike (OR = 0.49, 95% CI: 0.24, 0.98). The decreased risk associations were also conserved among human papillomavirus negative individuals. There was no evidence for statistical interaction with smoking on additive or multiplicative scales for any of the variants analyzed. Of CYP and GST polymorphisms detected in Canadian Caucasians, only GSTP1 105Val was associated with a decreased risk for SCCHN.

Differential impact of socioeconomic position across life on oral cancer risk in Kerala, India: An investigation of life-course models under a time-varying framework.

OBJECTIVES: The incidence of oral cancer has been rapidly increasing in India, calling for evidence contributing to a deeper understanding of its determinants. Although disadvantageous life-course socioeconomic position (SEP) is independently associated with the risk of these cancers, the explanatory mechanisms remain unclear. Possible pathways may be better understood by testing which life-course model most influences oral cancer risk. We estimated the association between life-course SEP and oral cancer risk under three life-course models: critical period, accumulation and social mobility. METHODS: We recruited incident oral cancer cases (N = 350) and controls (N = 371) frequency-matched by age and sex from two main referral hospitals in Kozhikode, Kerala, India, between 2008 and 2012. We collected information on childhood (0-16 years), early adulthood (17-30 years) and late adulthood (above 30 years) SEP and behavioural factors along the life span using interviews and a life-grid technique. Odds ratios (OR) and 95% confidence intervals (CI) were estimated for the association between life-course SEP and oral cancer risk using inverse probability weighted marginal structural models. RESULTS: Relative to an advantageous SEP in childhood and early adulthood, a disadvantageous SEP was associated with oral cancer risk [(OR = 2.76, 95% CI: 1.99, 3.81) and (OR = 1.84, 95% CI: 1.21, 2.79), respectively]. In addition, participants who were in a disadvantageous (vs advantageous) SEP during all three periods of life had an increased oral cancer risk (OR = 4.86, 95% CI: 2.61, 9.06). The childhood to early adulthood social mobility model and overall life-course trajectories indicated strong influence of exposure to disadvantageous SEP in childhood on the risk for oral cancer. CONCLUSIONS: Using novel approaches to existing methods, our study provides empirical evidence that disadvantageous childhood SEP is critical for oral cancer risk in this population from Kerala, India.

Periodontal diseases and risk of oral cancer in Southern India: Results from the HeNCe Life study.

Some studies suggest that periodontal diseases increase the risk of oral cancer, but contradictory results also exist. Inadequate control of confounders, including life course exposures, may have influenced prior findings. We estimate the extent to which high levels of periodontal diseases, measured by gingival inflammation and recession, are associated with oral cancer risk using a comprehensive subset of potential confounders and applying a stringent adjustment approach. In a hospital-based case-control study, incident oral cancer cases (N = 350) were recruited from two major referral hospitals in Kerala, South India, from 2008 to 2012. Controls (N = 371), frequency-matched by age and sex, were recruited from clinics at the same hospitals. Structured interviews collected information on several domains of exposure via a detailed life course questionnaire. Periodontal diseases, as measured by gingival inflammation and gingival recession, were evaluated visually by qualified dentists following a detailed protocol. The relationship between periodontal diseases and oral cancer risk was assessed by unconditional logistic regression using a stringent empirical selection of potential confounders corresponding to a 1% change-in-estimates. Generalized gingival recession was significantly associated with oral cancer risk (Odds Ratio = 1.83, 95% Confidence Interval: 1.10-3.04). No significant association was observed between gingival inflammation and oral cancer. Our findings support the hypothesis that high levels of periodontal diseases increase the risk of oral cancer.

No role for human papillomavirus infection in oral cancers in a region in southern India.

Oral cancer is a major public health issue in India with ∼ 77,000 new cases and 52,000 deaths yearly. Paan chewing, tobacco and alcohol use are strong risk factors for this cancer in India. Human papillomaviruses (HPVs) are also related to a subset of head and neck cancers (HNCs). We examined the association between oral HPV and oral cancer in a sample of Indian subjects participating in a hospital-based case-control study. We recruited incident oral cancer cases (N = 350) and controls frequency-matched by age and sex (N = 371) from two main referral hospitals in Kerala, South India. Sociodemographic and behavioral data were collected by interviews. Epithelial cells were sampled using Oral CDx® brushes from the oral cancer site and the normal mucosa. Detection and genotyping of 36 HPV genotypes were done using a polymerase chain reaction protocol. Data collection procedures were performed by qualified dentists via a detailed protocol with strict quality control, including independent HPV testing in India and Canada. HPV DNA was detected in none of the cases or controls. Associations between oral cancer and risk factors usually associated with HPV infection, such as oral sex and number of lifetime sexual partners, were examined by logistic regression and were not associated with oral cancer. Lack of a role for HPV infection in this study may reflect cultural or religious characteristics specific to this region in India that are not conducive to oral HPV transmission. A nationwide representative prevalence study is needed to investigate HPV prevalence variability among Indian regions.

Maternal and paternal contribution to intergenerational psychosocial transmission of paan chewing.

OBJECTIVES: Paan chewing is a recognized risk factor for oral cancer in the Asian population. However, there is currently little evidence about the intergenerational psychosocial transmission of paan chewing in South Indian families. We investigated the association between parental and participant's paan chewing in a South Indian population. METHODS: A subset of data was drawn from a hospital-based case-control study on oral cancer, the HeNCe Life study, conducted at Government Dental and Medical Colleges of Kozhikode, South India. Analyses were based on 371 noncancer control participants having diseases unrelated to known risk factors for oral cancer. Demographics, behavioral habits (e.g., paan chewing, smoking), and indicators of socioeconomic position (SEP) of both participants and their parents were collected with the use of a questionnaire-based interview and a life grid technique. Unconditional logistic regression assessed odds ratios (OR) and 95% confidence intervals (95% CI) for the associations between parental and participant's paan chewing, adjusted for confounders. RESULTS: Over half of the participants were males (55.2%), and the mean age of participants was 59 (SD = 12) years. After adjusting for age, religion, parents' SEP, parents' education, smoking and alcohol consumption, and perceived parenting behavior, we observed that maternal paan chewing and paternal paan chewing were significantly associated with the participant's paan chewing ([OR = 2.40, 95% CI = 1.11-5.21] and [OR = 3.05, 95% CI = 1.48-6.27], respectively). CONCLUSIONS: Intergenerational psychosocial transmission of the habit of paan chewing could occur through shared sociocultural or environmental factors.