Rice consumption and incidence of bladder cancer in a United States population

To the Editor:

Inorganic arsenic (i-As) is an established human bladder carcinogen¹. Generally, diet is considered the primary source of i-As for the U.S. and other populations around the world with access to relatively low arsenic drinking water^2,3. Ingested i-As from rice is estimated to dominate the exposure². Thus, we hypothesized that rice consumption may be related to bladder cancer incidence. Bladder cancer is a common malignancy in the U.S., and elevated bladder cancer incidence and mortality rates are reported in northern New England, largely attributed to drinking arsenic-contaminated water from private unregulated wells⁴. To date, very little epidemiologic research exists on the potential oncogenic role of rice as a source of i-As exposure⁵. As part of a U.S. population-based case–control study of bladder cancer, we assessed the association between rice intake and bladder cancer incidence. Using adjusted logistic regression models we estimated the odds ratios (OR) and 95% confidence intervals (CI) for rice consumption overall, by rice type (i.e., polished/white or brown rice), and rice consumption level (i.e., ≤20 g/day or >20 g/day), and stratified by household tap water arsenic (i.e., <1 μg/L or ≥1 μg/L) (Table and eTable 2 in the online supplemental material).

Table.

Odds ratios and 95% confidence intervals for bladder cancer according to rice consumption, and the arsenic concentration in household tap water.

Rice consumption	All water arsenic concentrations			<1 μg/L Water arsenic			≥1 μg/L Water arsenic
	Controls (n = 230)	Cases (n = 316)	OR (95% CI)(b)	Controls (n = 181)	Cases (n = 212)	OR (95% CI)(c)	Controls (n = 47)	Cases (n = 79)	OR (95% CI)(c)
None	50 (22)(e)	88 (28)	1.00 (referent)	40 (22)	63 (30)	1.00 (referent)	10 (21)	15 (19)	1.00 (referent)
Any rice(a)	180 (78)	228 (72)	0.8 (0.5 – 1.3)	141 (78)	149 (70)	0.7 (0.4 – 1.1)	37 (79)	64 (81)	1.3 (0.4 – 3.5)
White rice(a)	99 (43)	128 (40)	0.8 (0.5 – 1.4)	75 (41)	91 (43)	0.7 (0.4 – 1.3)	23 (49)	29 (37)	0.8 (0.3 – 2.6)
Brown rice (a,d)	81 (35)	100 (32)	0.8 (0.5 – 1.5)	66 (37)	58 (27)	0.6 (0.3 – 1.2)	14 (30)	35 (44)	2.3 (0.6 – 9.3)

OR = odds ratio, CI = confidence interval.

^(a)Any frequency.

^(b)OR were adjusted for age group, gender, caloric intake, cigarette smoking status, education, water arsenic concentration in μg/L, as well as quintiles of the “alternative Health Eating Index 2010” determined from the control distribution⁸.

^(c)OR were not adjusted for water arsenic concentration in μg/L.

^(d)Brown rice could include a mixture of brown and white rice.

^(e)n (%). 27 Study participants were missing household tap water arsenic concentrations. See eTable 2 for further details.

Our study population provided informed consent in accordance with the Committee for the Protection of Human Subjects at Dartmouth College. The population comprised bladder cancer cases (n = 316) identified through the New Hampshire State Department of Health and Human Services’ Cancer Registry and controls (n = 230) selected from lists of New Hampshire residents obtained from the New Hampshire Department of Transportation (<65 years) and Medicare enrollment lists (≥65 years)⁶. We used a validated food frequency questionnaire that covered participants’ diets during the past year to assess rice consumption (eFigure 1). Further details about the study population are also available in the supplemental material (eTable 1).

Overall, 72% of cases and 78% of controls reported rice consumption (OR = 0.8, 95% CI: 0.5–1.3). However, among those with higher water arsenic the odds ratio was somewhat elevated (OR = 1.3, 95% CI: 0.4–3.5) and similar to that reported previously⁵ but with limited statistical precision. Indeed, to our knowledge, the only prior study that investigated the relation between bladder cancer risk and rice consumption reported a pooled relative risk of 1.3 and 95% CI: 1.0–1.8 for rice consumed ≥5 times per week compared to rice consumed <1 per week among women from the Nurses’ Health Study and men from the Health Professionals Follow-up Study⁵. Our study found evidence of an interaction between brown rice consumption and water arsenic concentrations particularly for high consumers of brown rice (p = 0.003) (eTable 2). Overall, brown rice consumption was associated with an elevated odds ratio among those with greater than 1 μg/L water arsenic (OR = 2.3, 95% CI: 0.6–9.3), but again with wide confidence intervals (Table and eTable 2). A conceivable explanation for our findings could be related to the typically higher i-As content of brown rice compared to white rice and, the potential increase of i-As burden in ready-to-eat rice if arsenic-contaminated cooking water is used^2,7.

While our findings do not provide clear evidence that rice contributes to the overall incidence of bladder cancer, the potential risk of brown rice consumption in the presence of elevated water arsenic warrants further investigation in larger studies.